Clinical trial NCT01126541: SMART Study: A Study of Re-treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on Anti-TNF Alfa Therapy
Official title: A Comparative Study to Assess the Effect of Retreatment With 2 Doses of MabThera on Disease Activity Score in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response or Intolerance to antiTNF-alfa Therapy.(SMART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-05-19
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare the efficacy and safety of re-treatment with 2 doses of MabThera (rituximab) in patients with active rheumatoid arthritis (RA) who have previously experienced an inadequate response or intolerance to anti-tumor necrosis factor (anti-TNF) therapies etanercept, infliximab or adalimumab therapy. All patients will receive infusions of 1000 mg intravenous (IV) MabThera on Days 1 and 15; at Week 24 patients who have demonstrated a moderate or good response will be randomized to receive re-treatment with either 1 or 2 additional infusions of 1000 mg IV MabThera. The anticipated time on study treatment is 2+ years, and the target sample size is 100-500 individuals.


Eligibility criteria: Inclusion Criteria:

* Adult patients \>18 years of age
* RA for \>=6 months
* Receiving outpatient treatment
* Ongoing treatment with methotrexate for \>=3 months, stable for \>=1 month
* Inadequate response or intolerance to etanercept, infliximab or adalimumab

Exclusion Criteria:

* Previous treatment with MabThera
* Concurrent treatment with any anti TNF-alfa therapy or biologic therapy
* Previous treatment with any investigational cell-depleting therapies

Primary outcomes:
measure: Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104
timeFrame: Week 104
Secondary outcomes:
measure: DAS28-CRP During the Initial Treatment
timeFrame: Days 1 and 15, and Weeks 6, 12, and 24
measure: DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course
timeFrame: Day 1, 24 weeks following each infusion up to 72 Weeks
measure: Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2)
timeFrame: Week 24 of the Initial Treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment
measure: DAS28-CRP AUC Weighted Time
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Time to Achieve DAS28-CRP Remission After the First Course
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Time to Achieve DAS28-CRP Remission After Retreatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Time to Achieve DAS28-CRP ≤3.2 After the First Course of Treatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Time to Achieve DAS28-CRP ≤3.2 After Retreatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Duration of DAS28-CRP Remission After the First Course of Treatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Duration of DAS28-CRP Remission After Retreatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Duration of DAS28-CRP ≤3.2 After the First Course of Treatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Duration of DAS28-CRP ≤3.2 After Retreatment
timeFrame: Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
measure: Percentage of Participants Achieving American College of Rheumatology 20%, 50%, and 70% Improvement (ACR20/ACR50/ACR70)
timeFrame: Week 24 of the initial treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment
measure: Percentage of Participants Achieving a Response During Initial Treatment by European League Against Rheumatism (EULAR) Category
timeFrame: Day 15, Weeks 6, 12, and 24
measure: Percentage of Participants Achieving a Response During Retreatment by EULAR Category
timeFrame: Week 24, 24 weeks after 1st retreatment, 24 weeks after 2nd retreatment
measure: Percentage of Participants With Rheumatoid Factor (RF) at 24 Weeks After Treatment
timeFrame: Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment
measure: Percentage of Participants With Anti-cyclic Citrullinated Protein (Anti-CCP) Antibodies at 24 Weeks After Treatment
timeFrame: Week 24 of the initial treatment, 24 weeks after first re-treatment, and 24 weeks after second retreatment
measure: Physician's Global Assessment of Disease Activity
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Patient Global Assessment of Disease Activity
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Patient's Global Assessment of Pain
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Participant Assessment of Fatigue
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Cortisone Intake AUC (Time- and Weight-Weighted)
timeFrame: Day 1 (each infusion), Week 24, Week 104
measure: Total Mean Dose of Cortisone Between Week 24 and Week 104
timeFrame: Week 24 to Week 104
measure: HAQ-DI Scores
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Short Form 12 (SF-12) Physical Health Composite Score
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: SF-12 Mental Health Composite Score
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Medical Outcomes Study Sleep Scale (MOS-Sleep) Composite Sleep Problems 6 (SLP6) Index
timeFrame: Day 1 and Week 24 of initial treatment, before 1st retreatment, at 1st retreatment, and at 12 and 24 weeks after 1st retreatment
measure: Percentage of Participants Reporting Acceptable Disease Activity Symptom State Assessed Using Patient Acceptable and Unacceptable Symptom State (PASS)
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Patient Global Assessment of Disease Activity in Participants Reporting Acceptable Symptoms Using PASS
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Percentage of Participants With Minimum Clinically Important Improvement (MCII) in Disease Activity
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Change From Baseline in Patient Global Assessment of Disease Activity in Participants With MCII
timeFrame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment
measure: Percentage of Participants Reporting Acceptable Symptom State in Functioning Assessed Using PASS
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: HAQ-DI Scores in Participants Reporting Acceptable Function Using PASS
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Percentage of Participants With MCII in Functioning
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Change From Baseline in HAQ-DI in Participants With MCII
timeFrame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment
measure: Percentage of Participants With Acceptable Symptom State in Pain Assessed Using PASS
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Patient Global Assessment of Pain in Participants Reporting Acceptable Symptoms Using PASS
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Percentage of Participants With MCII in Pain
timeFrame: Week 24, 12 and 24 weeks after 1st retreatment
measure: Change From Baseline in Patient Global Assessment of Pain in Participants With MCII
timeFrame: Baseline, Week 24, 12 and 24 weeks after 1st retreatment
Other outcomes:
Locations:
city: Abbeville
country: France
city: Agen
country: France
city: Aix En Provence
country: France
city: Aix Les Bains
country: France
city: Amiens
country: France
city: Belfort
country: France
city: Berck
country: France
city: Bobigny
country: France
city: Bois-guillaume
country: France
city: Boulogne-billancourt
country: France
city: Brest
country: France
city: Caen
country: France
city: Cahors
country: France
city: Clermont-ferrand
country: France
city: Corbeil-essonnes
country: France
city: Echirolles
country: France
city: La Roche Sur Yon
country: France
city: Le Kremlin Bicetre
country: France
city: Libourne
country: France
city: Lievin
country: France
city: Lille
country: France
city: Limoges
country: France
city: Lomme
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Montivilliers
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Narbonne
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: PAU
country: France
city: Perpignan
country: France
city: Pessac
country: France
city: Pierre Benite
country: France
city: Poitiers
country: France
city: Reims
country: France
city: Rennes
country: France
city: Saint-etienne
country: France
city: Strasbourg
country: France
city: Toulon
country: France
city: Toulouse
country: France
city: Toulouse
country: France
city: Valence
country: France
city: Valenciennes
country: France
city: Vandoeuvre-les-nancy
country: France
city: Vannes
country: France
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_CHAIR
References:
citation: de Jong TD, Sellam J, Agca R, Vosslamber S, Witte BI, Tsang-A-Sjoe M, Mantel E, Bijlsma JW, Voskuyl AE, Nurmohamed MT, Verweij CL, Mariette X. A multi-parameter response prediction model for rituximab in rheumatoid arthritis. Joint Bone Spine. 2018 Mar;85(2):219-226. doi: 10.1016/j.jbspin.2017.02.015. Epub 2017 Mar 28.
citation: Sellam J, Riviere E, Courties A, Rouzaire PO, Tolusso B, Vital EM, Emery P, Ferraccioli G, Soubrier M, Ly B, Hendel Chavez H, Taoufik Y, Dougados M, Mariette X. Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis. Arthritis Res Ther. 2016 Dec 13;18(1):294. doi: 10.1186/s13075-016-1190-z.
citation: Sellam J, Rouanet S, Hendel-Chavez H, Miceli-Richard C, Combe B, Sibilia J, Le Loet X, Tebib J, Jourdan R, Dougados M, Taoufik Y, Mariette X. CCL19, a B cell chemokine, is related to the decrease of blood memory B cells and predicts the clinical response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2013 Sep;65(9):2253-61. doi: 10.1002/art.38023.
citation: Mariette X, Rouanet S, Sibilia J, Combe B, Le Loet X, Tebib J, Jourdan R, Dougados M. Evaluation of low-dose rituximab for the retreatment of patients with active rheumatoid arthritis: a non-inferiority randomised controlled trial. Ann Rheum Dis. 2014 Aug;73(8):1508-14. doi: 10.1136/annrheumdis-2013-203480. Epub 2013 May 30.
citation: Sellam J, Rouanet S, Hendel-Chavez H, Abbed K, Sibilia J, Tebib J, Le Loet X, Combe B, Dougados M, Mariette X, Taoufik Y. Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2011 Dec;63(12):3692-701. doi: 10.1002/art.30599.
citation: Sellam J, Hendel-Chavez H, Rouanet S, Abbed K, Combe B, Le Loet X, Tebib J, Sibilia J, Taoufik Y, Dougados M, Mariette X. B cell activation biomarkers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Arthritis Rheum. 2011 Apr;63(4):933-8. doi: 10.1002/art.30233.