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Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis

4 mars 2015 mis à jour par: Bristol-Myers Squibb

A Phase IIIB, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Comparative Study of Abatacept or Infliximab in Combination With Methotrexate in Controlling Disease Activity in Subjects With Rheumatoid Arthritis Having an Inadequate Clinical Response to Methotrexate

The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

431

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
    • Gauteng
      • Muckleneuk, Gauteng, Afrique du Sud
        • Local Institution
    • Kwa Zulu Natal
      • Berea, Kwa Zulu Natal, Afrique du Sud
        • Local Institution
    • Western Cape
      • Panorama, Western Cape, Afrique du Sud
        • Local Institution
  • Argentine
      • Buenos Aires, Argentine
        • Local Institution
      • Cordoba, Argentine
        • Local Institution
      • Tucuman, Argentine
        • Local Institution
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentine
        • Local Institution
      • Quilmes, Buenos Aires, Argentine
        • Local Institution
  • Australie
    • Queensland
      • Cairns, Queensland, Australie
        • Local Institution
      • Cotton Tree, Queensland, Australie
        • Local Institution
    • Victoria
      • Clayton, Victoria, Australie
        • Local Institution
      • Heidelberg, Victoria, Australie
        • Local Institution
      • Malvern, Victoria, Australie
        • Local Institution
      • Parkville, Victoria, Australie
        • Local Institution
    • Western Australia
      • Perth, Western Australia, Australie
        • Local Institution
  • Brésil
      • Rio De Janeiro, Brésil
        • Local Institution
      • Sao Paulo, Brésil
        • Local Institution
    • Parana
      • Curitiba, Parana, Brésil
        • Local Institution
    • Pernambuco
      • Recife, Pernambuco, Brésil
        • Local Institution
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brésil
        • Local Institution
  • Canada
      • Kitchener, Canada, ON
        • Local Institution
    • Alberta
      • Calgary, Alberta, Canada
        • Local Institution
      • Edmonton, Alberta, Canada
        • Local Institution
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Local Institution
    • Newfoundland and Labrador
      • St. Johns, Newfoundland and Labrador, Canada
        • Local Institution
    • Ontario
      • Hamilton, Ontario, Canada
        • Local Institution
      • Kitchener, Ontario, Canada
        • Local Institution
      • Ottawa, Ontario, Canada
        • Local Institution
    • Quebec
      • Montreal, Quebec, Canada
        • Local Institution
      • Ste-Foy, Quebec, Canada
        • Local Institution
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
        • Local Institution
  • Corée, République de
      • Seoul, Corée, République de
        • Local Institution
  • Danemark
      • Copenhagen, Danemark
        • Local Institution
  • Espagne
      • A Coruna, Espagne
        • Local Institution
      • Barcelona, Espagne
        • Local Institution
      • Cordoba, Espagne
        • Local Institution
      • Madrid, Espagne
        • Local Institution
  • Fédération Russe
      • Moscow, Fédération Russe
        • Local Institution
  • Mexique
      • San Luis Potosi, Mexique
        • Local Institution
    • Baja California
      • Tijuana, Baja California, Mexique
        • Local Institution
    • Distrito Federal
      • Mexico, Distrito Federal, Mexique
        • Local Institution
    • Guanajuato
      • Leon, Guanajuato, Mexique
        • Local Institution
    • Jalisco
      • Guadalajara, Jalisco, Mexique
        • Local Institution
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexique
        • Local Institution
  • Pologne
      • Poznan, Pologne
        • Local Institution
      • Sopot, Pologne
        • Local Institution
      • Warszawa, Pologne
        • Local Institution
  • Porto Rico
      • Rio Piedras, Porto Rico
        • Local Institution
  • Pérou
      • Lima, Pérou
        • Local Institution
  • République tchèque
      • Prague 2, République tchèque
        • Local Institution
  • Suisse
      • Bern, Suisse
        • Local Institution
      • St. Gallen, Suisse
        • Local Institution
  • Suède
      • Falun, Suède
        • Local Institution
      • Linkoping, Suède
        • Local Institution
      • Lund, Suède
        • Local Institution
      • Stockholm, Suède
        • Local Institution
      • Uppsala, Suède
        • Local Institution
  • États-Unis
    • Alabama
      • Huntsville, Alabama, États-Unis
        • Local Institution
    • Colorado
      • Denver, Colorado, États-Unis
        • Local Institution
    • Florida
      • Boca Raton, Florida, États-Unis
        • Local Institution
      • Ft Lauderdale, Florida, États-Unis
        • Local Institution
      • Largo, Florida, États-Unis
        • Local Institution
    • Indiana
      • Indianapolis, Indiana, États-Unis
        • Local Institution
    • Louisiana
      • New Orleans, Louisiana, États-Unis
        • Local Institution
    • Massachusetts
      • Springfield, Massachusetts, États-Unis
        • Local Institution
      • Worcester, Massachusetts, États-Unis
        • Local Institution
    • Mississippi
      • Flowood, Mississippi, États-Unis
        • Local Institution
    • New York
      • Syracuse, New York, États-Unis
        • Local Institution
    • North Carolina
      • Charlotte, North Carolina, États-Unis
        • Local Institution
    • Ohio
      • Cincinnati, Ohio, États-Unis
        • Local Institution
    • Oklahoma
      • Oklahoma City, Oklahoma, États-Unis
        • Local Institution
      • Tulsa, Oklahoma, États-Unis
        • Local Institution
    • Pennsylvania
      • Bethlehem, Pennsylvania, États-Unis
        • Local Institution
      • Willow Grove, Pennsylvania, États-Unis
        • Local Institution
    • Texas
      • Austin, Texas, États-Unis
        • Local Institution
      • Dallas, Texas, États-Unis
        • Local Institution

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 à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Diagnosis of Rheumatoid Arthritis
  • At least 3 months prior treatment with Methotrexate (MTX)
  • At least 10 swollen joints and 12 tender joints and C-Reactive Protein of at least 1 mg/dl
  • Washout required for other disease modifying anti-rheumatic drugs (DMARDS)

Exclusion Criteria:

  • participants who have failed more than 3 DMARDs
  • participants previously treated with an approved biologic drug
  • History of cancer in the last 5 years
  • Severe or recurrent bacterial infection
  • Any previous or current medical conditions that are contraindications to the use of TNF blocking agents
  • Women of Child Bearing Potential

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: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: Abatacept (ABA) + Methotrexate (MTX) (double-blind [DB])
Days 1-365
Médicament: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
Abatacept, intravenous (IV) Solution, Infusion, Depends on participant weight, Monthly, 12 months.
Autres noms:
  • Orencia
Comparateur actif: Infliximab + MTX (DB)
Days 1-365
Médicament: Infliximab (INF) + MTX, DB
Infliximab, IV Solution, Infusion, Depends on participant weight, Every 2 Months, 12 months.
Comparateur placebo: Placebo + MTX (DB)
Days 1-197
Médicament: Placebo (PLA) + MTX, DB
Placebo, IV Solution, Infusion, Depends on participant weight, Monthly, 6 months.
Expérimental: Placebo + MTX switched to abatacept + MTX (DB)
Participants received placebo plus methotrexate for days 1-197, and abatacept plus methotrexate for days 198-365
Médicament: PLA + MTX switched to ABA+ MTX, DB
Placebo=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months. Abatacept=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months
Autres noms:
  • Orencia
Expérimental: Abatacept (open-label)
Days 365 to 729 All participants receive Active Drug
Médicament: ABA, open-label (OL)
Abatacept, IV solution, Infusion. Depends on participant weight, Monthly, 12+ months
Autres noms:
  • Orencia

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis)
Délai: Baseline (Day 1), 6 months (Day 197)
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or C-reactive protein (CRP), and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Baseline (Day 1), 6 months (Day 197)
OL; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, and AEs Leading to Discontinuation
Délai: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
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 beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
OL; Number of Participants With AEs of Special Interest
Délai: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
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. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
OL; Number of Participants With Select Hematologic Laboratory Abnormalities
Délai: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; monocytes: >2000 mm3; eosinophils: >0.750 x 10^3 c/uL;
From Day 366 through end of OL (range from 1.9 months to 42.3 months)
OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
Délai: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL
From Day 366 through end of OL (range from 1.9 months to 42.3 months)
OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
Délai: Baseline (Day 1), Day 365
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Platelets
Délai: Baseline (Day 1), Day 365
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Hematocrit
Délai: Baseline (Day 1), Day 365
Hematocrit: <0.75 x BL
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in White Blood Cells
Délai: Baseline (Day 1), Day 365
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Erythrocytes
Délai: Baseline (Day 1), Day 365
Erythrocytes: <0.75 x BL
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Electrolytes
Délai: Baseline (Day 1), Day 365
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Délai: Baseline (Day 1), Day 365
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Délai: Baseline (Day 1), Day 365
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Baseline (Day 1), Day 365
OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
Délai: Baseline (Day 1), Day 729
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Platelets
Délai: Baseline (Day 1), Day 729
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Hematocrit
Délai: Baseline (Day 1), Day 729
Hematocrit: <0.75 x BL
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in White Blood Cells
Délai: Baseline (Day 1), Day 729
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Erythrocytes
Délai: Baseline (Day 1), Day 729
Erythrocytes: <0.75 x BL
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Electrolytes
Délai: Baseline (Day 1), Day 729
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Délai: Baseline (Day 1), Day 729
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Délai: Baseline (Day 1), Day 729
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Baseline (Day 1), Day 729
OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
Délai: Baseline (Day 1), Day 1121
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Platelets
Délai: Baseline (Day 1), Day 1121
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Hematocrit
Délai: Baseline (Day 1), Day 1121
Hematocrit: <0.75 x BL
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in White Blood Cells
Délai: Baseline (Day 1), Day 1121
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Erythrocytes
Délai: Baseline (Day 1), Day 1121
Erythrocytes: <0.75 x BL
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Electrolytes
Délai: Baseline (Day 1), Day 1121
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Délai: Baseline (Day 1), Day 1121
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Délai: Baseline (Day 1), Day 1121
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Baseline (Day 1), Day 1121
OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
Délai: Baseline (Day 1), Day 1513
Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Platelets
Délai: Baseline (Day 1), Day 1513
Platelets (PLT): <0.67 x LLN, >1.5 x ULN
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Hematocrit
Délai: Baseline (Day 1), Day 1513
Hematocrit: <0.75 x BL
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in White Blood Cells
Délai: Baseline (Day 1), Day 1513
Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Erythrocytes
Délai: Baseline (Day 1), Day 1513
Erythrocytes: <0.75 x BL
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Electrolytes
Délai: Baseline (Day 1), Day 1513
Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
Délai: Baseline (Day 1), Day 1513
Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;
Baseline (Day 1), Day 1513
OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
Délai: Baseline (Day 1), Day 1513
alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN
Baseline (Day 1), Day 1513
OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
Délai: Days 365, 729, 1121, and 1513
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)
Days 365, 729, 1121, and 1513
OL; Mean Heart Rate (HR) During Open Label Period
Délai: Days 365, 729, 1121, and 1513
Heart Rate (HR), units=beats per minute (bpm)
Days 365, 729, 1121, and 1513
OL; Mean Temperature (T) During Open Label Period
Délai: Days 365, 729, 1121, and 1513
Temperature (T), units=degrees Celcius
Days 365, 729, 1121, and 1513

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
Délai: Baseline (Day 1), 6 months (Day 197)
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Baseline (Day 1), 6 months (Day 197)
DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
Délai: From Day 1 through Day 365 (12 months)
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). Clinically significant response= decrease in DAS28 score of >1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.
From Day 1 through Day 365 (12 months)
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
Délai: DB Day 197
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.
DB Day 197
DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
Délai: DB Day 365
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.
DB Day 365
DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
Délai: Baseline (Day 1), 6 months (Day 197)
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.
Baseline (Day 1), 6 months (Day 197)
DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
Délai: Baseline (Day 1), 12 months (Day 365)
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.
Baseline (Day 1), 12 months (Day 365)
DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
Délai: Baseline (Day 1), 6 months (Day 197)
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Baseline (Day 1), 6 months (Day 197)
DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
Délai: Baseline (Day 1), 12 months (Day 365)
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Baseline (Day 1), 12 months (Day 365)
DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
Délai: DB Day 365
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL)
DB Day 365
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
Délai: DB Day 197
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
DB Day 197
DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
Délai: DB Day 365
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
DB Day 365
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 197
Délai: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
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 Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
Délai: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
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. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 365
Délai: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
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 Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Délai: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
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 198 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
Délai: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
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. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
Délai: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
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. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).
From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
Délai: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
Délai: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
Délai: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.
From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
Délai: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
Délai: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL
From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
Délai: Day 1 through day 365
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 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.
Day 1 through day 365
DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
Délai: Day 1 through day 365
Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.
Day 1 through day 365
OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
Délai: Baseline (Day 1), Day 365, Day 533, Day 729
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Baseline (Day 1), Day 365, Day 533, Day 729
OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
Délai: Baseline (Day 1), Day 365, Day 533, Day 729
The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.
Baseline (Day 1), Day 365, Day 533, Day 729
OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
Délai: DB Days 365, 533, and 729
The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute >5.1 or <0.6 change from BL)
DB Days 365, 533, and 729
OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
Délai: DB Day 197, Day 365, Day 533, Day 729
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.
DB Day 197, Day 365, Day 533, Day 729
OL; Percentage of Participants Who Achieved Major Clinical Response
Délai: Defined from the date of achieving ACR 70 response to 6 months post response
Major Clinical Response was defined as a continuous ACR 70 for six months.
Defined from the date of achieving ACR 70 response to 6 months post response
OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
Délai: OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729
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.
OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729
OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
Délai: Day 1 (Baseline), Day 729
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.
Day 1 (Baseline), Day 729

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Bristol-Myers Squibb

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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 février 2005

Achèvement primaire (Réel)

1 juillet 2009

Achèvement de l'étude (Réel)

1 juillet 2009

Dates d'inscription aux études

Première soumission

1 novembre 2004

Première soumission répondant aux critères de contrôle qualité

1 novembre 2004

Première publication (Estimation)

2 novembre 2004

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

24 mars 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

4 mars 2015

Dernière vérification

1 mars 2015

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • IM101-043

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