Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis
9 dicembre 2015 aggiornato da: Bristol-Myers Squibb
A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults With Very Early RA
The primary purpose of the protocol is to demonstrate the ability of abatacept plus methotrexate to induce remission in patients with very early rheumatoid arthritis after 12 months of treatment and to maintain remission following 6 months of drug withdrawal.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
511
Fase
- Fase 3
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Queensland
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Cairns, Queensland, Australia, 4870
- Local Institution
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Maroochydore, Queensland, Australia, 4558
- Local Institution
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South Australia
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Woodville, South Australia, Australia, 5011
- Local Institution
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Victoria
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Heidelberg, Victoria, Australia, 3084
- Local Institution
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Malvern, Victoria, Australia, 3144
- Local Institution
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Western Australia
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Victoria Park, Western Australia, Australia, 6100
- Local Institution
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Bruxelles, Belgio, 1200
- Local Institution
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Kortrijk, Belgio, 8500
- Local Institution
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Merksem, Belgio, 2170
- Local Institution
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Alberta
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Calgary, Alberta, Canada, T2N 4N1
- Local Institution
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Quebec
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Laval, Quebec, Canada, H7T 2P5
- Local Institution
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Daegu, Corea, Repubblica di, 705-718
- Local Institution
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Daejeon, Corea, Repubblica di, 302-799
- Local Institution
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Seoul, Corea, Repubblica di, 137-701
- Local Institution
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Seoul, Corea, Repubblica di, 133-791
- Local Institution
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Hjorring, Danimarca, 9800
- Local Institution
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Moscow, Federazione Russa, 117049
- Local Institution
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Moscow, Federazione Russa, 129327
- Local Institution
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Tver, Federazione Russa, 170036
- Local Institution
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Helsinki, Finlandia, 00290
- Local Institution
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Tampere, Finlandia, 33521
- Local Institution
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Chambray Les Tours, Francia, 37170
- Local Institution
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Montpellier, Francia, 34295
- Local Institution
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Paris Cedex 14, Francia, 75679
- Local Institution
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Poitiers, Francia, 86021
- Local Institution
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Berlin, Germania, 10117
- Local Institution
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Berlin, Germania, 14059
- Local Institution
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Hildesheim, Germania, 31134
- Local Institution
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Muenchen, Germania, 80336
- Local Institution
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Muenchen, Germania, 80639
- Local Institution
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Muenchen, Germania, 81541
- Local Institution
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Ancona, Italia, 60055
- Local Institution
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Siena, Italia, 53100
- Local Institution
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Chihuahua, Messico, 31000
- Local Institution
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Queretaro, Messico, 76178
- Local Institution
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San Luis Potosi, Messico, 78240
- Local Institution
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Estado De Mexico
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Metepec, Estado De Mexico, Messico, 52140
- Local Institution
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Jalisco
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Guadalajara, Jalisco, Messico, 44500
- Local Institution
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Guadalajara, Jalisco, Messico, 44690
- Local Institution
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Nuevo Leon
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Monterrey, Nuevo Leon, Messico, 64020
- Local Institution
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Yucatan
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Merida, Yucatan, Messico, 97000
- Local Institution
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Lublin, Polonia, 20-954
- Local Institution
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Poznan, Polonia, 60-218
- Local Institution
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Torun, Polonia, 87100
- Local Institution
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Warszawa, Polonia, 01-157
- Local Institution
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Warszawa, Polonia, 01-868
- Local Institution
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Wroc#aw, Polonia, 50-088
- Local Institution
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Alabama
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Huntsville, Alabama, Stati Uniti, 35801
- Rheumatology Associates Of North Alabama, P.C.
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Arkansas
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Hot Springs, Arkansas, Stati Uniti, 71913
- St. Joseph'S Mercy Clinic
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Florida
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Sarasota, Florida, Stati Uniti, 34239
- Sarasota Arthritis Research Center
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Idaho
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Coeur D Alene, Idaho, Stati Uniti, 83814
- Coeur D'Alene Arthrit Clin
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Maryland
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Baltimore, Maryland, Stati Uniti, 21224
- Johns Hopkins University Division of Rheumatology
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Massachusetts
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Worcester, Massachusetts, Stati Uniti, 01605
- Clinical Pharmacology Study Group
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Mississippi
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Jackson, Mississippi, Stati Uniti, 39202
- Arthritis Associates Of Mississippi
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Nebraska
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Lincoln, Nebraska, Stati Uniti, 68516
- Physician Research Collaboration, LLC
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North Carolina
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Hickory, North Carolina, Stati Uniti, 28602
- Piedmont Rheumatology, Pa
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Wilmington, North Carolina, Stati Uniti, 28401
- Carolina Arthritis Associates
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Ohio
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Cleveland, Ohio, Stati Uniti, 44109
- MetroHealth Medical Center
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Middleburg, Ohio, Stati Uniti, 44130
- Isam A. Diab, Md
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Pennsylvania
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Duncansville, Pennsylvania, Stati Uniti, 16635
- Alan J. Kivitz, Md, Cpi
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South Carolina
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Orangeburg, South Carolina, Stati Uniti, 29118
- Mitchell C. Feinman, Md
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Wisconsin
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Glendale, Wisconsin, Stati Uniti, 53217
- Kurt Oelke, Md
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Gauteng
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Kempton Park, Gauteng, Sud Africa, 1619
- Local Institution
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Pretoria, Gauteng, Sud Africa, 0083
- Local Institution
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Pretoria, Gauteng, Sud Africa, 0084
- Local Institution
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Pretoria, Gauteng, Sud Africa, 0181
- Local Institution
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Kwa Zulu Natal
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Durban, Kwa Zulu Natal, Sud Africa, 4001
- Local Institution
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Western Cape
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Panorama, Western Cape, Sud Africa, 7500
- Local Institution
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Goteborg, Svezia, 413 45
- Local Institution
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Linkoping, Svezia, 581 85
- Local Institution
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Malmo, Svezia, 205 02
- Local Institution
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Stockholm, Svezia, 171 76
- Local Institution
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Uppsala, Svezia, 751 85
- Local Institution
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Key Inclusion Criteria:
- Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening
- Onset of persistent symptoms ≤ 2 years prior to screening
- Positive test result for anticyclic citrullinated peptides 2
- Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit
- Biologic naive, including no treatment with an investigational biologic prior to screening
- Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening
- Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization
- If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks
- Able to undergo magnetic resonance imaging
Key Exclusion Criteria:
- Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)
- Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization
- Scheduled for or anticipating joint replacement surgery
- Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator
- History of malignancy in the last 5 years
- Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection
- At risk for tuberculosis
- Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore attivo: Abatacept, 125 mg, plus methotrexate, 2.5 mg
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
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Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months
Altri nomi:
Tablets, oral, 2.5 mg, once weekly, 12 months
Altri nomi:
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Comparatore attivo: Methotrexate, 2.5 mg, plus abatacept placebo
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
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Tablets, oral, 2.5 mg, once weekly, 12 months
Altri nomi:
Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months
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Comparatore attivo: Abatacept, 125 mg, plus methotrexate placebo
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
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Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months
Altri nomi:
Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
Lasso di tempo: Randomization to Months 12 and 18
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DAS28-CRP remission defined as <2.6;
TP=treatment phase; WP=withdrawal phase.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
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Randomization to Months 12 and 18
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
Lasso di tempo: Randomization to Months 12 and 18
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TP=treatment period; WP=withdrawal period.
Remission defined as DAS28-CRP<2.6.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
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Randomization to Months 12 and 18
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Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population
Lasso di tempo: Randomization to Month 24
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TP=treatment period; WP=withdrawal period.
Remission defined as DAS28-CRP<2.6.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
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Randomization to Month 24
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Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18
Lasso di tempo: Baseline to Month 18
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TP=treatment period; WP=withdrawal period.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
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Baseline to Month 18
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Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18
Lasso di tempo: Randomization to Month 18
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TP=treatment period; WP=withdrawal period.
SDAI-defined remission= ≤3.3.
The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL).
SDAI total score=0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity.
TJC is assessed and recorded at each visit, with no swelling=0, swelling=1.
SJC is assessed through identification of joints that are painful under pressure or to passive motion.
TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1.
Higher score indicates greater affection due to disease activity.
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Randomization to Month 18
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Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time
Lasso di tempo: Randomization to Month 18
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TP=treatment period; WP=withdrawal period.
The SDAI is the simple linear sum of 5 outcome parameters: swollen joint count (SJC) and tender joint count (TJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL).
SDAI total score=0-86.
SJC is assessed and recorded at each visit, with no swelling=0, swelling=1 (higher score indicates greater swelling).
TJC is assessed at each visit through identification of joints that are painful under pressure or to passive motion, with no tenderness=0, tenderness=1 (higher score indicates greater affection due to disease activity)..
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Randomization to Month 18
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Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time
Lasso di tempo: Randomization to Month 24
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HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses patients' functional ability by rating their abilities over the previous week.
The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities.
Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do.
The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3.
When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.
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Randomization to Month 24
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Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time
Lasso di tempo: Randomization to Month 18
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The Health Assessment Questionnaire Disability Index (HAQ-DI) assesses patients' functional ability by rating their abilities over the previous week.
The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities.
Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do.
The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3.
When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.
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Randomization to Month 18
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Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)
Lasso di tempo: Randomization to Months 6, 12, and 18
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TP=treatment period; WP=withdrawal period.
The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales.
Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health).
Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.
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Randomization to Months 6, 12, and 18
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Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)
Lasso di tempo: Randomization to Month 18
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TP=treatment period; WP=withdrawal period.
Change from Baseline=Postbaseline-baseline value.
MRI was used to assess joint damage progression at Months 6, 12, and 18.
If >20% of joints with a missing score for a parameter (erosion, osteitis, and synovitis), the MRI score of each parameter was considered missing.
If ≤20% of joints had a missing score for a parameter, the MRI score for that parameter from the missing joints was carried forward from the previous MRI assessment, or carried backward from the next MRI assessment, if missing score occurred at baseline.
MRI total score ranged from 0 (best outcome) to 4 (worst outcome).
A gadolinium-enhanced MRI of the dominant hand-wrist was performed on all randomized patients at 5 points.
The hand/wrist assessed to have more synovitis was selected initially and used for all subsequent evaluations.
The MRI examination was standardized to ensure sufficient image quality for the evaluation of radiographic progression of rheumatoid arthritis.
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Randomization to Month 18
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Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period
Lasso di tempo: Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Related=having certain, probable, possible, or unknown relationship to study drug.
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Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
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Adverse Events (AEs) of Interest During the Treatment Period
Lasso di tempo: Day 1 to 56 days following last dosing day (Day 365)
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Related=having certain, probable, possible, or unknown relationship to study drug.
AEs of special interest are events potentially associated with the drug or disease under study.
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Day 1 to 56 days following last dosing day (Day 365)
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Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period
Lasso di tempo: Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
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Lower limit of normal (LLN); Upper limit of normal (ULN); Pretreatment (preRX).
Criteria for marked abnormality: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN,
or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
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Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
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Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12
Lasso di tempo: End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
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WP=withdrawal period.
Remission defined as DAS28-CRP<2.6.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.).
Percentage= number of participants with remission divided by number of participants who were analyzed (all treated participants who were in remission at end of treatment period and entered the Withdrawal Period)
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End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
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Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period
Lasso di tempo: Randomization to Month 24
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TP=treatment period; WP=withdrawal period.
SDAI-defined remission= ≤3.3.
The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL).
SDAI total score=0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity.
TJC is assessed and recorded at each visit, with no swelling=0, swelling=1.
SJC is assessed through identification of joints that are painful under pressure or to passive motion.
TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1.
Higher score indicates greater affection due to disease activity.
Percent=number with remission/number evaluated (ITT)
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Randomization to Month 24
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Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)
Lasso di tempo: Day 1 to 56 days post last dose in the study, up to Month 30
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Includes data up to last active dose date +56 days if the participant discontinued the Treatment Period or did not enter the Withdrawal Period, up to the day of discontinuation in the Withdrawal Period for participants discontinuing the Withdrawal Period without entering the Re-exposure Period (RP), up to Day 729 visit (Month 24) for participants who complete the Withdrawal Period, and up to 56 days post last active dose in Re-exposure Period for participants entering the Re-exposure Period.
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Day 1 to 56 days post last dose in the study, up to Month 30
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Adverse Events (AEs) of Interest During the Withdrawal Period
Lasso di tempo: Last dose in TP + 57 days, up to Month 24
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
AEs of special interest are events potentially associated with the drug or disease under study.
Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period and up to end of Withdrawal Period.
Treatment groups represent treatment received during the Treatment Period.
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Last dose in TP + 57 days, up to Month 24
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Adverse Events (AEs) of Interest During the Re-exposure Period
Lasso di tempo: First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
AEs of special interest are events potentially associated with the drug or disease under study.
Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period.
Treatment groups represent Treatment received during Treatment Period.
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First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days
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Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period
Lasso di tempo: Last dose in TP + 57 days, up to Month 24
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LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment.
Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase (GGT) (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN,
or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
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Last dose in TP + 57 days, up to Month 24
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Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period
Lasso di tempo: Start of re-exposure period to 56 days post last dose, up to Month 30
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LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment.
Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN,
or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
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Start of re-exposure period to 56 days post last dose, up to Month 30
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- Ahmad HA, Baker JF, Conaghan PG, Emery P, Huizinga TWJ, Elbez Y, Banerjee S, Østergaard M. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022 Feb 16;24(1):47. doi: 10.1186/s13075-022-02735-8.
- Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.
- Ahmad HA, Baker JF, Ostergaard M, Ye J, Emery P, Conaghan PG. Determining MRI Inflammation Targets When Considering a Rheumatoid Arthritis Treat-to-Target Strategy: Results of a Randomized, Placebo-Controlled Trial. Adv Ther. 2019 Sep;36(9):2384-2393. doi: 10.1007/s12325-019-01020-6. Epub 2019 Jul 5.
- Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Maldonado MA, Huizinga TW. Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study. RMD Open. 2019 Feb 8;5(1):e000840. doi: 10.1136/rmdopen-2018-000840. eCollection 2019.
- Bykerk VP, Burmester GR, Combe BG, Furst DE, Huizinga TWJ, Ahmad HA, Emery P. On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis. Rheumatol Int. 2018 Dec;38(12):2225-2231. doi: 10.1007/s00296-018-4173-3. Epub 2018 Oct 20. Erratum In: Rheumatol Int. 2019 Feb 5;:
- Peterfy C, Burmester GR, Bykerk VP, Combe BG, DiCarlo JC, Furst DE, Huizinga TW, Wong DA, Conaghan PG, Emery P. Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. Ann Rheum Dis. 2016 Aug;75(8):1501-5. doi: 10.1136/annrheumdis-2015-208258. Epub 2016 Feb 10.
- Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barre E, Karyekar CS, Wong DA, Huizinga TW. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015 Jan;74(1):19-26. doi: 10.1136/annrheumdis-2014-206106. Epub 2014 Nov 3.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 dicembre 2010
Completamento primario (Effettivo)
1 settembre 2013
Completamento dello studio (Effettivo)
1 ottobre 2014
Date di iscrizione allo studio
Primo inviato
3 giugno 2010
Primo inviato che soddisfa i criteri di controllo qualità
10 giugno 2010
Primo Inserito (Stima)
11 giugno 2010
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
14 gennaio 2016
Ultimo aggiornamento inviato che soddisfa i criteri QC
9 dicembre 2015
Ultimo verificato
1 dicembre 2015
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Malattie autoimmuni
- Malattie articolari
- Malattie muscoloscheletriche
- Malattie reumatiche
- Malattie del tessuto connettivo
- Artrite
- Artrite, reumatoide
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Agenti antireumatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti dermatologici
- Inibitori del checkpoint immunitario
- Agenti di controllo riproduttivo
- Agenti abortivi, non steroidei
- Agenti abortivi
- Antagonisti dell'acido folico
- Metotrexato
- Abatacept
Altri numeri di identificazione dello studio
- IM101-226
- 2010-018674-20 (Numero EudraCT)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .