Overview

This trial has been completed.

Condition rheumatoid arthritis
Treatments placebo, tocilizumab, methotrexate
Phase phase 3
Sponsor Hoffmann-La Roche
Start date November 2013
End date October 2016
Trial size 718 participants
Trial identifier NCT01855789, ML28776

Summary

This randomized, multicenter, double-blind, parallel group study will evaluate the impact of MTX discontinuation on the efficacy of subcutaneous tocilizumab (RoActemra/Actemra) in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to current MTX therapy. Participants will be initiated on tocilizumab 162 milligrams (mg) weekly or every 2 weeks, remaining on a stable dose of MTX. At Week 24, participants achieving DAS28 less than or equal to (

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
All enrolled participants will receive TCZ 162 mg weekly or every 2 weeks along with MTX at a stable dose for 24-week. Participants who do not achieve a DAS28 score </=3.2 at Week 24 will continue the same treatment in a non-randomized open label manner. Participants who achieve a DAS28 score </=3.2 at Week 24 will receive the randomized double blind treatment according to the arm in which they are randomized.
tocilizumab RoActemra/Actemra
Participants will receive tocilizumab 162 mg subcutaneously weekly (in participants weighing >/= 100 kg) or 162 mg subcutaneously every 2 weeks (in participants weighing <100 kg).
methotrexate
Participants will receive stable oral dose of MTX (15 to 25 mg/week).
(Experimental)
Participants who complete the initial 24-week treatment with TCZ + MTX and achieve a DAS28 score </=3.2 at Week 24 will be randomized to receive TCZ 162 mg weekly or every 2 weeks along with MTX up to Week 52.
tocilizumab RoActemra/Actemra
Participants will receive tocilizumab 162 mg subcutaneously weekly (in participants weighing >/= 100 kg) or 162 mg subcutaneously every 2 weeks (in participants weighing <100 kg).
methotrexate
Participants will receive stable oral dose of MTX (15 to 25 mg/week).
(Active Comparator)
Participants who complete the initial 24-week treatment with TCZ + MTX and achieve a DAS28 score </=3.2 at Week 24 will be randomized to receive TCZ 162 mg weekly or every 2 weeks along with MTX placebo up to Week 52.
placebo
Participants will receive methotrexate matching placebo.
tocilizumab RoActemra/Actemra
Participants will receive tocilizumab 162 mg subcutaneously weekly (in participants weighing >/= 100 kg) or 162 mg subcutaneously every 2 weeks (in participants weighing <100 kg).

Primary Outcomes

Measure
Change from Week 24 in disease activity score based on 28 joints count (DAS28) score at Week 40
time frame: Week 24, Week 40

Secondary Outcomes

Measure
Percentage of participants achieving American college of rheumatology 50% improvement (ACR50) responses
time frame: Weeks 40 and 52
Percentage of participants with >/= 1.2 points worsening (increase) in DAS28 Score
time frame: Weeks 24 to 40, Weeks 24 to 52
Percentage of participants achieving DAS28 score <2.6
time frame: Weeks 40 and 52
Percentage of participants achieving DAS 28 score </= 3.2
time frame: Weeks 40 and 52
Percentage of participants achieving American college of rheumatology 20% improvement (ACR20) responses
time frame: Weeks 40 and 52
Percentage of participants achieving American college of rheumatology 70% improvement (ACR70) responses
time frame: Weeks 40 and 52
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
time frame: Baseline up to 60 weeks
Change from Week 24 in bone erosion score (as measured by magnetic resonance imaging [MRI]) for participants in the MRI substudy
time frame: Weeks 24, 40
Percentage of participants with anti-tocilizumab (TCZ) antibodies
time frame: Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)
Mean TCZ concentration
time frame: Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)
Mean soluble interleukin-6 (IL-6) receptor concentration
time frame: Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Body weight /=] 4.4) according to the revised 1987 American College of Rheumatology (ACR) criteria at screening and baseline (prior to treatment on Day 1) - Currently receiving oral MTX for at least 24 weeks and on a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1), with the following exception: a stable dose of at least 10 mg/week is allowed for participants with a body weight less than (<) 50 kg or calculated glomerular filtration rate (or creatinine clearance) <60 milliliters per minute (mL/min) - History of parenteral (subcutaneous or intramuscular) MTX is allowed, but not within 6 weeks prior to treatment (Day 1). Participants must not have a documented, clinically significant intolerance to oral MTX and must be receiving oral MTX at a dose of 15 mg/week for at least 6 weeks prior to treatment (Day 1) - Prior to enrollment, have discontinued etanercept for >/=2 weeks, infliximab, certolizumab, adalimumab, or golimumab for >/=8 weeks - Oral corticosteroids must have been /=15 mg/week - Participants receiving other (non-MTX) disease modifying anti-rheumatic drugs (DMARDs) within 8 weeks of screening - Previous treatment with abatacept, rituximab, tofacitinib, or anakinra - Treatment with intrarticular or parenteral corticosteroids within 4 weeks prior to treatment - Previous treatment with cell-depleting therapies or alkylating agents - Previous treatment with tocilizumab - Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 12 months following randomization - Rheumatic autoimmune disease other than rheumatoid arthritis - Non-rheumatic autoimmune diseases (e.g. inflammatory bowel diseases, psoriasis, multiple sclerosis) - Prior history of or current inflammatory joint disease other than rheumatoid arthritis - Functional Class IV according to the revised (1987) ACR criteria for rheumatoid arthritis - History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies - Evidence of significant uncontrolled concomitant diseases; uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids - Active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening - Active tuberculosis requiring treatment within the previous 3 years - History of or currently active primary or secondary immunodeficiency - Pregnant or breast-feeding women - Positive for hepatitis B or hepatitis C infection - For potential MRI substudy participants: the presence of any metal-containing device or object in the body

Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.