SMART Study: A Study of Re-treatment With MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on Anti-TNF Alfa Therapy
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)
1 other identifier
interventional
224
1 country
53
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 rheumatoid-arthritis
Started Sep 2006
Longer than P75 for phase_3 rheumatoid-arthritis
53 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2006
CompletedFirst Submitted
Initial submission to the registry
May 18, 2010
CompletedFirst Posted
Study publicly available on registry
May 19, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2011
CompletedResults Posted
Study results publicly available
September 15, 2014
CompletedSeptember 15, 2014
September 1, 2014
5.2 years
May 18, 2010
July 15, 2014
September 10, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (DAS28-CRP) Area Under the Curve (AUC) at Week 104
DAS28-CRP was based on joint counts, overall participant assessment, and serum CRP levels (measured in milligrams per liter \[mg/L\]) at each visit. Joint counts included swollen joint count (SJC) and tender joint count (TJC). Total score range was 0 to 9.4; a higher score indicated more disease activity. DAS28-CRP less than or equal to (≤)3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity, and less than (\<)2.6 equals (=) remission. The AUC of all DAS28-CRP values between Day 1 and Week 104 (15 values of protocol visits) was calculated using the trapeze method (AUC between t1 and t2=(t2-t1)\*((DAS28-CRP at t1 + DAS28-CRP at t2)/2). The true visit dates were used to calculate the time between 2 DAS28-CRP evaluations. All the AUC were censored at Week 104 (linear extrapolation using the 2 last DAS28-CRP values (Weeks 96 and 104) to obtain the "true" DAS28-CRP value at the "true" Week 104).
Week 104
Secondary Outcomes (39)
DAS28-CRP During the Initial Treatment
Days 1 and 15, and Weeks 6, 12, and 24
DAS28-CRP and Changes From Baseline to Week 24 in DAS28-CRP by Retreatment Course
Day 1, 24 weeks following each infusion up to 72 Weeks
Percentage of Participants Achieving Clinical Remission (DAS28-CRP <2.6) or Low Disease Activity (DAS28-CRP ≤3.2)
Week 24 of the Initial Treatment, 24 weeks after first retreatment, and 24 weeks after second retreatment
DAS28-CRP AUC Weighted Time
Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
Time to Achieve DAS28-CRP Remission After the First Course
Days 1 and 15, Weeks 6, 12, and 24 and every 8 weeks thereafter through Week 104
- +34 more secondary outcomes
Study Arms (2)
A
EXPERIMENTAL1000 mg IV rituximab
B
EXPERIMENTAL2 x 1000 mg IV rituximab
Interventions
Arm A: 1000 mg IV (one infusion) every 2 months \\nArm B: 2 x 1000 mg IV (2 infusions) every 2 months
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Previous treatment with MabThera
- Concurrent treatment with any anti TNF-alfa therapy or biologic therapy
- Previous treatment with any investigational cell-depleting therapies
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (53)
Unknown Facility
Abbeville, 80142, France
Unknown Facility
Agen, 47923, France
Unknown Facility
Aix-en-Provence, 13616, France
Unknown Facility
Aix-les-Bains, 73106, France
Unknown Facility
Amiens, 80054, France
Unknown Facility
Belfort, 90016, France
Unknown Facility
Berck, 62600, France
Unknown Facility
Bobigny, 93009, France
Unknown Facility
Bois-Guillaume, 76233, France
Unknown Facility
Boulogne-Billancourt, 92104, France
Unknown Facility
Brest, 29609, France
Unknown Facility
Caen, 14033, France
Unknown Facility
Cahors, 46005, France
Unknown Facility
Clermont-Ferrand, 63003, France
Unknown Facility
Corbeil-Essonnes, 91106, France
Unknown Facility
Échirolles, 38434, France
Unknown Facility
La Roche-sur-Yon, 85925, France
Unknown Facility
Le Kremlin-Bicêtre, 94275, France
Unknown Facility
Libourne, 33505, France
Unknown Facility
Liévin, 62800, France
Unknown Facility
Lille, 59037, France
Unknown Facility
Limoges, 87042, France
Unknown Facility
Lomme, 59462, France
Unknown Facility
Lyon, 69365, France
Unknown Facility
Marseille, 13013, France
Unknown Facility
Montivilliers, 76290, France
Unknown Facility
Montpellier, 34295, France
Unknown Facility
Nantes, 44035, France
Unknown Facility
Narbonne, 11108, France
Unknown Facility
Nice, 06202, France
Unknown Facility
Paris, 75019, France
Unknown Facility
Paris, 75475, France
Unknown Facility
Paris, 75571, France
Unknown Facility
Paris, 75651, France
Unknown Facility
Paris, 75674, France
Unknown Facility
Paris, 75679, France
Unknown Facility
Paris, 75877, France
Unknown Facility
Pau, 64046, France
Unknown Facility
Perpignan, 66046, France
Unknown Facility
Pessac, 33600, France
Unknown Facility
Pierre-Bénite, 69495, France
Unknown Facility
Poitiers, 86021, France
Unknown Facility
Reims, 51100, France
Unknown Facility
Rennes, 35203, France
Unknown Facility
Saint-Etienne, 4200, France
Unknown Facility
Strasbourg, 67098, France
Unknown Facility
Toulon, 83100, France
Unknown Facility
Toulouse, 31054, France
Unknown Facility
Toulouse, 31059, France
Unknown Facility
Valence, 26000, France
Unknown Facility
Valenciennes, 59322, France
Unknown Facility
Vandœuvre-lès-Nancy, 54511, France
Unknown Facility
Vannes, 56017, France
Related Publications (6)
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.
PMID: 28363827DERIVEDSellam 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.
PMID: 27964756DERIVEDSellam 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.
PMID: 23740460DERIVEDMariette 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.
PMID: 23723317DERIVEDSellam 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.
PMID: 22127692DERIVEDSellam 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.
PMID: 21225699DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Nonserious adverse events (AEs) presented in this record include all AEs reported during the study, not just nonserious events.
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-LaRoche
Study Officials
- STUDY CHAIR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 18, 2010
First Posted
May 19, 2010
Study Start
September 1, 2006
Primary Completion
November 1, 2011
Study Completion
November 1, 2011
Last Updated
September 15, 2014
Results First Posted
September 15, 2014
Record last verified: 2014-09