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Phase IIIB Subcutaneous Missed Dose Study

22 avril 2015 mis à jour par: Bristol-Myers Squibb

A Phase IIIb, Multi-Center, Randomized, Withdrawal Study to Evaluate the Immunogenicity and Safety of Subcutaneous Administered Abatacept in Adults With Active Rheumatoid Arthritis

The purpose of the study is to determine whether subcutaneous abatacept administered to patients with rheumatoid arthritis is associated with increased immunogenicity or increased safety events upon withdrawal and reintroduction.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

270

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Afrique du Sud
    • Free State
      • Bloemfontein, Free State, Afrique du Sud, 9317
        • Local Institution
    • Gauteng
      • Muckleneuk, Gauteng, Afrique du Sud, 0002
        • Local Institution
      • Pretoria, Gauteng, Afrique du Sud, 0084
        • Local Institution
    • Kwa Zulu Natal
      • Berea, Kwa Zulu Natal, Afrique du Sud, 4001
        • Local Institution
    • Western Cape
      • Panorama, Western Cape, Afrique du Sud, 7500
        • Local Institution
  • Argentine
      • Cordoba, Argentine, 5000
        • Local Institution
      • Santa Fe, Argentine, 3000
        • Local Institution
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentine, 1015
        • Local Institution
    • Santa Fe
      • Rosario, Santa Fe, Argentine, 2000
        • Local Institution
  • Canada
    • Quebec
      • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
        • Local Institution
  • Mexique
    • Distrito Federal
      • Mexico City, Distrito Federal, Mexique, 06726
        • Local Institution
    • Estado De Mexico
      • Metepec, Estado De Mexico, Mexique, 52140
        • Local Institution
    • Guanajuato
      • Leon, Guanajuato, Mexique, 37520
        • Local Institution
    • Yucatan
      • Merida, Yucatan, Mexique, 97000
        • Local Institution
  • États-Unis
    • California
      • Los Angeles, California, États-Unis, 90048
        • Wallace Rheumatic Study Center
    • Connecticut
      • Trumbull, Connecticut, États-Unis, 06611
        • New England Research Associates, LLC
    • Florida
      • Sarasota, Florida, États-Unis, 34239
        • Sarasota Arthritis Research Center
    • Indiana
      • Indianapolis, Indiana, États-Unis, 46227
        • Diagnostic Rheumatology And Research,Pc
    • Maryland
      • Cumberland, Maryland, États-Unis, 21502
        • Klein And Associates, M.D., Pa
    • Massachusetts
      • Worcester, Massachusetts, États-Unis, 01610
        • Clinical Pharmacology Study Group
    • Minnesota
      • Eagan, Minnesota, États-Unis, 55121
        • St. Paul Rheumatology, P.A.
    • New Mexico
      • Albuquerque, New Mexico, États-Unis, 87102
        • Albuquerque Clinical Trials, Inc.
    • Pennsylvania
      • Bethlehem, Pennsylvania, États-Unis, 18015
        • East Penn Rheumatology Associates
      • Duncansville, Pennsylvania, États-Unis, 16635
        • Altoona Center for Clinical Research
      • Erie, Pennsylvania, États-Unis, 16508
        • Center For Assessment And Research Of Erie
    • South Carolina
      • Columbia, South Carolina, États-Unis, 29204
        • Columbia Arthritis Center
    • West Virginia
      • Clarksburg, West Virginia, États-Unis, 26301
        • Mountain State Clinical Research

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Clinical diagnosis of Rheumatoid Arthritis
  • Disease Activity Score (DAS)28-C-Reactive Protein (CRP) score ≥ 3.2 and ≤5.1
  • On background methotrexate at least 3 months (≥10mg weekly)
  • Must be able to self injection or allow a care giver to do it for them
  • Discontinue all Biologics and Disease-Modifying Anti-rheumatic Drugs (DMARDs) except for methotrexate

Exclusion Criteria:

  • Participants who had prior exposure to abatacept or CTLA-4 Ig
  • Received treatment with rituximab.
  • Participants who have received treatment with leflunomide within 1 year of screening
  • Participants who have received treatment with immunoadsorption columns (such as Prosorba columns), mycophenolate mofetil (Cellcept®), cyclosporine A or other calcineurin inhibitors, or D-Penicillamine.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: Placebo
Médicament: Placebo
Solution in pre-filled syringes, Subcutaneously, 0 mg, Weekly, Period II 12 weeks (Short Term)
Expérimental: Abatacept
Médicament: Abatacept
Solution in pre-filled syringes, Subcutaneously, 125 mg, Weekly, (Short Term (3 periods - 12 weeks each; Long Term)
Autres noms:
  • Orencia
  • BMS-188667

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Double-blind Withdrawal (DBW) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibody Responses by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 169
Délai: Day 169
Serum samples from all treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using an enzyme-linked immunosorbent assay (ELISA). Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Day 169
Re-introduction (RI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Groups
Délai: Day 253 (short term)
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Day 253 (short term)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Placebo Group
Délai: Day 253 (short term)
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Day 253 (short term)
Lead-in (LI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time
Délai: For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug
LI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) Over Time
Délai: For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug
ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time
Délai: Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody. Samples were obtained during treatment (TRT) visits.
Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Post Visits
Délai: Day 22 after last dose of drug to Day 85 after last dose of drug
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Day 22 after last dose of drug to Day 85 after last dose of drug
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time
Délai: Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL At Post Visits
Délai: Day 22 after last dose of drug to Day 85 after last dose of drug
ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
Day 22 after last dose of drug to Day 85 after last dose of drug
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time by DBW Treatment Group
Délai: For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time by DBW Treatment Group
Délai: For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug
ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug
Short Term (ST); Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ELISA Antibody Responses by DBW Treatment Groups
Délai: For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug
Serum samples from Abatacept-treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody. ST was defined as the LI Period, the DBW Period, and the RI Period (Days 1-253).
For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug
Short Term: Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ECL Antibody Responses by DBW Treatment Groups
Délai: For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug
ECL screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNC) Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing or negative.
For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug
Short Term: Mean Change in Disease Activity Score (DAS) 28 (Using C-Reactive Protein [CRP]) From Baseline Over Time by DBW Treatment Groups
Délai: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
The DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
Short Term: Percentage of Participants Achieving Clinically Meaningful Improvement (CMI) in DAS 28 (CRP), Low Disease Activity (LDAS), or Clinical Remission Over Time by DBW Treatment Groups
Délai: Days 85, 169, and 253 (short term)
DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Days 85, 169, and 253 (short term)
Short Term; Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline Over Time by DBW Treatment Groups
Délai: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
Short Term; Percentage of Participants With HAQ-DI Response Over Time by DBW Treatment Groups
Délai: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.
Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)
LI; Mean Change in DAS 28 (CRP) From Baseline Over Time
Délai: Days 1 (Baseline), 15, 29, 57, 78, 85
DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Days 1 (Baseline), 15, 29, 57, 78, 85
LI; Percentage of Participants With Clinically Meaningful Improvement in DAS (CRP) Over Time
Délai: Days 15, 29, 57, 78, 85
DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Days 15, 29, 57, 78, 85
DBW Period; Mean Change in DAS 28 (CRP) From DBW Period Baseline (Day 85) Over Time
Délai: Days 85 (Period 2 Baseline), 113, 141, and 169
DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Days 85 (Period 2 Baseline), 113, 141, and 169
DBW Period; Percentage of Participants With Rheumatoid Arthritis (RA) Flare Over Time
Délai: Days 85, 113, 141, and 169

A participant had an RA flare if at least 2 of the following criteria were met:

  • Doubling of tender and swollen joint count from Day 78
  • Increase in DAS28-CRP score ≥ 1.2 from Day 78
  • Prematurely discontinued from Double-blind Withdrawal Period (Period 2) and continued to Re-introduction Period (Period 3)
Days 85, 113, 141, and 169
RI Period; Mean Change in DAS 28 (CRP) From RI Period Baseline (Day 169) Over Time
Délai: Days 169 (Period III Baseline), 197, 225, and 253
DAS28 is a continuous disease measure composite of 4 variables: the number of tender joints out of 28 joints, the number of swollen joints out of 28 joints, the level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. DAS28 has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Clinically meaningful improvement= decrease in DAS28 score of ≥1.2 from baseline.
Days 169 (Period III Baseline), 197, 225, and 253
LI; Number of Participants With Deaths, Serious Adverse Events (SAEs), SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Délai: From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
LI Period; Number of Participants With AEs of Special Interest
Délai: From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion), peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion),local injection site reaction (pre-specified AEs occurring at the site of SC injection)and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
LI; Number of Participants With Hematology Values Meeting the Marked Abnormality (MA) Criteria
Délai: From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/ microliter (uL); eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
LI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
Délai: From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
LI; Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria
Délai: From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
LI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
Délai: From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*upper limits of normal (ULN),or if BL< lower limits of normal (LLN) then use 0.8*BL or > upper limits of normal (ULN),or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >ULN,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis: Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells (RBCs), White Blood Cells (WBCs):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier
LI Period; Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Délai: Days 1, 15, 29, 57, 78, and 85
Blood pressure was taken in participants while seated and measured in millimeters of mercury (mmHg). Pressures were assessed at screening, at baseline on Day 1 prior to infusion of IV abatacept, at 30 and 60 minutes after IV infusion of abatacept on Day 1, and at all office visits prior to SC injection of abatacept. Vital signs were also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 1, 15, 29, 57, 78, and 85
LI Period; Mean Heart Rate (HR)
Délai: Days 1, 15, 29, 57, 78, and 85
Heart rate was taken in participants while seated and measured in beats per minute (bpm). Heart rate was assessed at screening, at baseline on Day 1 prior to infusion of IV abatacept, at 30 and 60 minutes after IV infusion of abatacept on Day 1, and at all office visits prior to SC injection of abatacept. Heart rate was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 1, 15, 29, 57, 78, and 85
LI Period; Mean Temperature (T)
Délai: Days 1, 15, 29, 57, 78, and 85
Temperature was taken in participants while seated and measured in degrees celsius. Temperature was assessed at screening, at baseline on Day 1 prior to infusion of IV abatacept, at 30 and 60 minutes after IV infusion of abatacept on Day 1, and at all office visits prior to SC injection of abatacept. Temperature was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 1, 15, 29, 57, 78, and 85
DBW; Number of Participants With Death, Serious SAEs, Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
Délai: From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
DBW; Number of Participants With AEs of Special Interest
Délai: From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion), peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion),local injection site reaction (pre-specified AEs occurring at the site of SC injection)and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
DBW; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria
Délai: From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/uL; eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
DBW; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
Délai: From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
DBW; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria
Délai: From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
DBW; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
Délai: From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier
DBW; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Double Blind Period
Délai: Days 113, 141, and 169
Blood pressures were taken in participants while seated, just prior to study drug injection, and measured in millimeters of mercury (mmHg).
Days 113, 141, and 169
DBW Period; Mean Heart Rate (HR) During Period 2
Délai: Days 113, 141, and 169
Heart Rate was taken in participants while seated, just prior to study drug injection, and measured in beats per minute (bpm)
Days 113, 141, and 169
DBW Period; Mean Temperature (T) During Period II
Délai: Days 113, 141, and 169
Participants were seated and temperature taken just prior to study drug injection.
Days 113, 141, and 169
RI; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
Délai: From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
RI; Number of Participants With AEs of Special Interest
Délai: From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion), peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion),local injection site reaction (pre-specified AEs occurring at the site of SC injection)and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
RI; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria
Délai: From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/uL; eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
RI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria
Délai: From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
RI; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria
Délai: From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
RI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria
Délai: From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.
RI Period; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Period III
Délai: Days 169, 197, 225, and 253
Days 169, 197, 225, and 253
RI Period; Mean Heart Rate (HR) During Period III
Délai: Days 169, 197, 225, and 253
Days 169, 197, 225, and 253
RI Period; Mean Temperature (T) During Period III
Délai: Days 169, 197, 225, and 253
Days 169, 197, 225, and 253
Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ELISA by RI Treatment Groups
Délai: Day 197 through Day 253
Pharmacokinetics is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmin=minimum observed plasma concentration of single-dose abatacept. Cmin for each participant was listed by study visit and immunogenicity status (seropositive vs. seronegative) was determined by ELISA.
Day 197 through Day 253
Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ECL by RI Treatment Groups
Délai: Day 197 through Day 253
Pharmacokinetics is a branch of pharmacology concerned with the rate at which drugs are absorbed, distributed, metabolized, and eliminated by the body. Cmin=minimum observed plasma concentration of single-dose abatacept. Cmin for each participant was listed by study visit and immunogenicity status (seropositive vs. seronegative) was determined by ECL.
Day 197 through Day 253
ST; Number of Participants Positive for Anti-nuclear Antibody (ANA), Anti-double Stranded DNA Antibody (dsDNA), or Rheumatoid Factor (RF) at Day 253 According to Baseline Status (Negative at Baseline or Positive at Baseline) by DBW Treatment Groups
Délai: Baseline, Day 253
Venous blood was collected and tested for anti-nuclear antibodies, anti-dsDNA antibodies, and rheumatoid factor. ANA were detected by means of immunofluorescent antibodies. An anti-DNA radioimmunoassay was used for detection of anti-dsDNA antibodies (Diagnostic Products Corporation). RF was measured by an immunoturbidimetric assay (Roche Tina-Quant). Determinations of antibody or RF status were made at baseline and Day 253.
Baseline, Day 253
LTE: DAS28-CRP Mean Change From Baseline (Day 1) Over Time - All Participants Treated in LTE
Délai: For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.
DAS28=continuous disease measure composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28, level of serum reactant protein CRP, and participant global assessment of disease activity measured on a visual analogue scale. DAS28-CRP has numeric thresholds defining high disease activity (> 5.1), low disease activity (≤ 3.2) and remission (< 2.6). Last day of ST is Day 85 for Period I Nonresponders and Day 253 for ST Completers . Data are not available(NA) for the period from Day 113 to Day 253 for Period 1 non-responders. Note: Day 85 and Day 337 assessments for the Period I Nonresponder cohort in fact represent consecutive assessments with an interval of approximately 1 month. For Period I nonresponder, study days do not represent treatment days. Study Day 337 for a Period I nonresponder actually corresponds to that participant's Treatment Day 169.
For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.
LTE: Percent of Participants Who Achieved Clinical Remission in the Long Term Extension - All Participants Treated in LTE
Délai: For Period I non-responders: as of Study Day 85 and up to Study Day 1821. For ST completers: as of Study Day 253 and up to Study Day 1821
DAS28=continuous disease measure composite of 4 variables: number of tender joints out of 28, number of swollen joints out of 28, level of serum reactant protein CRP, and participant global assessment of disease activity measured on a visual analogue scale. Clinical remission=DAS28-CRP score<2.6. Percent=Number of participants meeting remission divided by number of participants evaluated. Last day of ST is Day 85 for Period I Nonresponders and Day 253 for ST Completers . Data are not available (NA) for the period from Day 113 to Day 253 for Period 1 non-responders. Note: Day 85 and Day 337 assessments for the Period I Nonresponder cohort in fact represent consecutive assessments with an interval of approximately 1 month. For Period I nonresponder, study days do not represent treatment days. Study Day 337 for a Period I nonresponder actually corresponds to that participant's Treatment Day 169.
For Period I non-responders: as of Study Day 85 and up to Study Day 1821. For ST completers: as of Study Day 253 and up to Study Day 1821
LTE: Percent of Participants With Low Disease Activity in Long Term Extension: All Participants Treated in LTE
Délai: For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.
DAS28:continuous disease measure composite of 4 variables: number of tender joints out of 28 joints, number of swollen joints out of 28 joints, level of the serum reactant protein CRP, and participant global assessment of disease activity measure on a visual analogue scale. Low disease activity score: ≤ 3.2. Percent=Number of participants with Low Disease Activity divided by number of participants evaluated. Last day of ST is Day 85 for Period I Nonresponders and Day 253 for ST Completers . Data are not available(NA) for the period from Day 113 to Day 253 for Period 1 non-responders. Note: Day 85 and Day 337 assessments for the Period I Nonresponder cohort in fact represent consecutive assessments with an interval of approximately 1 month. For Period I nonresponder, study days do not represent treatment days. Study Day 337 for a Period I nonresponder actually corresponds to that participant's Treatment Day 169.
For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.
LTE: Percent of Participants With HAQ Response Over Time - All Participants Treated in LTE
Délai: Study Days 1 (Baseline),15, 29, 57, 78, 85, 253, 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541,1625,1709,1821,1905,1989, 2073
The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index (DI) was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ DI. Percent=number of participants with HAQ response divided by number of participants in the analysis. Since Period I Non-responders proceeded directly to the LTE at the end of Period I (Day 85), study days do not represent treatment days.
Study Days 1 (Baseline),15, 29, 57, 78, 85, 253, 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541,1625,1709,1821,1905,1989, 2073
LTE: Overall Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses (ECL Method) for On-Treatment Visits, Post Last Dose Visits, and Overall Study - All Participants Treated in LTE
Délai: Days 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1457, 1625, 1821, 1989 and 28, 56, 85, 168 days post last dose in LTE
Serum samples from Abatacept-treated adult participants with active RA were screened for the presence of drug-specific antibodies using electrochemiluminescence (ECL). The percent of participants with a positive abatacept induced immunogenicity response against cytotoxic T-lymphocyte antigen 4 (CTLA4) and possibly immunoglobulin (Ig), or against Ig and/or Junction Region was calculated by number of participants with a positive response divided by number of participants evaluated. Overall for on-treatment includes treatment visits on Days 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1457, 1625, 1821, and 1989.
Days 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1457, 1625, 1821, 1989 and 28, 56, 85, 168 days post last dose in LTE
LTE: Number of Participants With Death, Related SAEs, SAEs Leading to Discontinuation, Related AEs, or AEs Leading to Discontinuation During Long Term Extension (LTE)
Délai: For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014), up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. SAEs include hospitalizations for elective surgical procedures.All deaths reported during the LTE including those that occurred > 56 days after the last dose. Related AE or SAE defined as AE or SAE with Certain, Probable, Possible, or Missing relationship to study medication. All participants who completed the ST period could enter the open label LTE on Day 253; LI Period 1 non-responders could directly enter the LTE.
For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014), up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.
LTE: Number of Participants With AEs of Special Interest During LTE
Délai: For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014) up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.
AEs of special interest in LTE are those AEs that may be associated with the use of immunomodulatory drugs, including all infections and opportunistic infections; autoimmune disorders; malignancies, local injection site reaction (pre-specified AEs occurring at the site of SC injection) and systemic injection site reactions (pre-specified systemic AEs such as hypersensitivity reactions occurring within 24 hours of SC injection)
For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014) up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.
LTE: Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria During LTE
Délai: For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Marked abnormality criteria are: Hemoglobin (HGB): >3 g/dL decrease from BL; Hematocrit: <0.75 * BL; Erythrocytes: <0.75 * BL; Platelets (PLT): <0.67 * LLN/>1.5 * ULN, or if BL < LLN then use <0.5 * BL and <100,000 mm^3; Leukocytes: <0.75 * LLN/ >1.25 * ULN, or if BL<LLN then use <0.8 * BL or >ULN, or if BL>ULN then use >1.2 * BL or <LLN; neutrophils+bands: <1.0 * 10^3 cells/uL; eosinophils: >0.750 * 10^3 cells/uL; basophils: > 400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750 * 10^3 cells/uL/ >7.50 * 10^3 cells/uL.
For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
LTE: Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria During LTE
Délai: For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
LTE: Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria During LTE
Délai: For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
LTE: Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria During LTE
Délai: For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.
LTE: Mean Seated Systolic Blood Pressure (SBP) During LTE
Délai: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073
During LTE, blood pressure was taken in participants while seated, measured in millimeters of mercury (mmHg) and were assessed at all office visits prior to SC injection of abatacept. Vital signs were also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073
LTE: Mean Seated Diastolic Blood Pressure (DBP) During LTE
Délai: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
During LTE, blood pressure was taken in participants while seated, measured in millimeters of mercury (mmHg) and were assessed at all office visits prior to SC injection of abatacept. Vital signs were also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
LTE: Mean Heart Rate (HR) During LTE
Délai: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
During LTE, heart rate was taken in participants while seated, measured in beats per minute (bpm) and was assessed at all office visits prior to SC injection of abatacept. Heart rate was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
LTE: Mean Temperature (T) During LTE
Délai: Days 337, 365, 449,533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073
During LTE, temperature was taken in participants while seated, measured in degrees celsius and was assessed at all office visits prior to SC injection of abatacept. Temperature was also assessed 7 days after the last injection of abatacept for participants who were withdrawn prematurely.
Days 337, 365, 449,533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073

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Parrainer

Bristol-Myers Squibb

Publications et liens utiles

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Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 novembre 2007

Achèvement primaire (Réel)

1 décembre 2008

Achèvement de l'étude (Réel)

1 février 2014

Dates d'inscription aux études

Première soumission

20 septembre 2007

Première soumission répondant aux critères de contrôle qualité

21 septembre 2007

Première publication (Estimation)

24 septembre 2007

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

23 avril 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

22 avril 2015

Dernière vérification

1 avril 2015

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • IM101-167

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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