Clinical trial NCT00299130: A Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate Compared to Methotrexate Alone in Patients With Active Rheumatoid Arthritis
Official title: A Randomized, Placebo Controlled, Double-blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate, Compared to Methotrexate Monotherapy, in Patients With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: RA
Rituxan
SERENE
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2006-03-06
Enrollment: 511
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).


Eligibility criteria: Inclusion criteria:

* Adult patients 18-80 years of age.
* Rheumatoid arthritis (RA) for ≥ 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis.
* Receiving outpatient treatment for RA.
* Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline.
* At screening, either

  * C-reactive protein (CRP) ≥ 0.6 mg/dL (6 mg/L), or
  * Erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour.
* Inadequate response to methotrexate, having received and tolerated at a dose of 10-25 mg/week it for ≥ 12 weeks.

Exclusion criteria:

* Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA.
* Inflammatory joint disease other than RA, or other systemic autoimmune disorder.
* Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16.
* Surgery within 12 weeks of study or planned within 24 weeks of randomization.
* Previous treatment with any approved or investigational biological agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy.

Primary outcomes:
measure: Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Percentage of Participants With an ACR50 Response at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With an ACR70 Response at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24
timeFrame: Baseline and Week 24
measure: Percent Change From Baseline in Swollen Joint Count
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Tender Joint Count
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Patient's Global Assessment of Disease Activity
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Patient's Pain Assessment
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Physician's Global Assessment of Disease Activity
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in C-Reactive Protein
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Erythrocyte Sedimentation Rate
timeFrame: Baseline, Week 24 and Week 48
measure: Percent Change From Baseline in Short Form 36 Health Survey (SF-36) Summary Scores (Physical and Mental Components)
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) General Health Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Bodily Pain Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Functioning Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Physical Role Limitations Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Health Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Vitality Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Social Functioning Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Short Form 36 Health Survey (SF-36) Emotional Role Limitations Domain Score
timeFrame: Baseline, Week 24 and Week 48
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scores
timeFrame: Baseline, Week 24 and Week 48
measure: Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With HAQ-DI Improved, Unchanged or Worsened at Week 48
timeFrame: Baseline and Week 48
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 48
timeFrame: Baseline and Week 48
measure: Percentage of Participants With DAS28-ESR Low Disease Activity Score and Clinical Remission at Week 48
timeFrame: Week 48
measure: Percentage of Participants With an ACR50 Response at Week 48
timeFrame: Baseline and Week 48
measure: Percentage of Participants With an ACR70 Response at Week 48
timeFrame: Baseline and Week 48
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, Latinis K, Abud-Mendoza C, Szczepanski LJ, Roschmann RA, Chen A, Armstrong GK, Douglass W, Tyrrell H. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010 Sep;69(9):1629-35. doi: 10.1136/ard.2009.119933. Epub 2010 May 20.
citation: Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum. 2011 Dec;63(12):3681-91. doi: 10.1002/art.30596.