A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX
Rheumatoid Arthritis
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Body weight </=150 kg
- Active moderate to severe rheumatoid arthritis (DAS28 >/=4.4) according to the revised 1987 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 <50 kg or calculated glomerular filtration rate (or creatinine clearance) <60 milliliters per minute (mL/min)
- History of parenteral (SC or intramuscular [IM]) 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)
- Participants who have received one prior anti-tumor necrosis factor (TNF) must have discontinued etanercept, infliximab, certolizumab, adalimumab, or golimumab for at least 6 months prior to screening
- Oral corticosteroids must have been </=10 mg/day prednisone (or equivalent) and stable for at least 25 out of 28 days prior to treatment (Day 1)
- Participants receiving treatment on an outpatient basis
Exclusion Criteria:
- Documented medical history of significant intolerance to oral MTX >/=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 parenteral corticosteroids within 4 weeks prior to treatment
- Previous treatment with cell-depleting therapies or alkylating agents
- Previous treatment with TCZ
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery during the study
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Non-rheumatic active autoimmune diseases (for example, 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
Sites / Locations
- Pinnacle Research Group; Llc, Central
- Uni Of Alabama,Birmingham; Medicine - Rheumatology
- Rheumatology Associates of North Alabama
- Clnical & Translational Reseach Center for Alabama, PC
- Arizona Arthritis & Rheumatology Associates, P.C.
- Arizona Arthritis & Rheumatology Research, Pllc
- Arizona Arthritis and Rheuma
- Valley Arthritis Care
- Advanced Arthritis Care & Research
- Fort Smith Rheumatology, PC
- CHI St. Vincent Medical Group Hot Springs
- NEA Baptist Clinic
- Little Rock Diagnostic Clinic
- Medvin Clinical Research
- TriWest Research Associates, LLC
- St. Jude Hospital Yorba Linda DBA St. Joseph
- CV Mehta MD Medical Corp
- Valerius Medical Group
- NRC Research Institute
- San Diego Arthritis Med Clnc
- C Michael Neuwelt MD Inc
- Inland Rheumatology; Clinical Trials, Inc.
- Medvin Clinical Research
- University of Colorado Hospital
- Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs
- Denver Arthritis Clinic
- Joao Nascimento
- Clinical Research Center of Ct/Ny
- Arthritis & Osteoporosis Center Pc
- New England Research Associates
- Rheumatolgy Consultants of Deleware
- Javed Rheumatology Associates, Inc.
- Arthritis & Rheumatism; Disease Specialities
- Robert Levin, Md; Research Dept
- Precision Research Organization
- Suncoast Research Group LLC
- South Coast Research Center, Inc.
- Jeffrey Alper M.D Research
- Rheumatology Associates of Central Florida
- Arthritis and Rheumatology Clinic
- Arthritis Center Palm Harbor
- Arthritis Rsrch of Florida, Inc.
- Pinellas Medical Research - Allegry & Rheumatology Associates, LLC
- Sarasota Arthritis Res Center
- West Broward Rheumatology Associates, Inc.
- McIlwain Medical Group
- Burnette & Silverfield, MDS
- Advanced Clinical Research of Orlando, Inc.
- North Georgia Rheumatology
- Arthritis Center of North Georgia
- North Georgia Rheumatology Group, PC
- Institute of Arthritis Research
- Springfield Clinic
- Indiana Uni Medical Center
- Diagnostic Rheumatology & Research
- Kansas City Internal Medicine
- Bluegrass Comm Research, Inc.
- Arthritis & Diabetes Clinic, Inc
- Klein & Associates, M.D., P.A.
- New England Medical Center; Dept. of Medicine, Div. of Rheumatology
- Phase Iii Clinical Research
- Mansfield Medical Center
- Reliant Medical Group, Inc; Rheumatology
- UMass Memorial Medical Center
- Clinical Pharmacology Study Group
- Advanced Rheumatology, PC
- Fiechtner Research Inc
- Nisus Research/Northern Michigan Hospital
- Shores Rheumatology
- St. Luke's Hospital Association of Duluth
- St. Paul Rheumatology
- Arthritis and Osteoporosis; Treatment and Research Center
- Jackson Arthritis Clinic
- David S Rosenberg
- Clinical Research Consultants,LLC
- Clayton Medical Research
- Arthritis Consultants
- G. T. Kelly, MD
- Rheumatology Research Group
- Nashua Rheumatology - Foundation Medical Partners
- Arthritis and Osteoporosis Associates
- Atlantic Coast Rheumatology
- Ocean Rheumatology
- Arthritis Rheumatic & Back Disease Associates
- Cooper Cancer Institute
- Albuquerque Clinical Trials
- Arthritis and Osteoporosis Associates of New Mexico
- The Center for Rheumatology
- Arthritis & Osteoporosis Center
- Manhasset Rheumatology
- Manhattan Medical Reserach
- Buffalo Rheumatology Associates
- Office of Premier Chatpar Md
- Rheumatology Associates of Long Island
- Arthritis Health Associates
- Asheville Arthritis & Osteoporosis Center, PA
- Carolina Bone & Joint P.A.
- Triangle Orthopaedics Associates, P.A.
- Medication Management
- PMG Research of Hickory LLC
- Cape Fear Arthritis Care
- Shanahan Rheumatology & Immunology, PLLC
- St. Alexius Medical Center; Arthritis Clinic
- Odyssey Research Services; Main Medical Building
- Crystal Arthritis Center, Inc.
- Cincinnati Rheumatic Disease Study Group
- University Hospitals Case Medical Center
- Ohio State University; Rheumatology; Immun/Rheum
- Columbus Arthritis Center
- STAT Research Inc
- Paramount Medical Research
- Clinical Research Source, Inc.
- Arthritis Care Center Oklahoma
- Arthritis and Rheumatology; Center of Oklahoma PLLC
- Health Research of Oklahoma, Llc
- Lynn Health Science Inst.
- Oklahoma Center For Arthritis Therapy & Research
- Healthcare Research Consultants
- Altoona Center For Clinical Research
- Arthritis Associates
- Arthritis Group
- Advanced Rheumatology & Arthritis Research Center
- Clinical Research Center of Reading
- Emkey Arthritis & Osteoporosis
- Low Country Rheumatology, PA
- Columbia Arthritis Center (Partnership Practice)
- Piedmont Arthritis Clinic
- West Tennessee Research Institute
- Ramesh Gupta - PP
- Amarillo Center For Clinical Research
- Austin Regional Clinic
- Lovelace Scientific Resources Inc.
- Diagnostic Group
- AOCBV
- Adriana Pop-Moody MD Clinic PA
- Arthritis Care & Diagnostic Center
- Metroplex Clinical Research
- Rheumatic Disease Clin Res Ctr
- IntraFusion Researh Network
- Houston Inst. For Clinical Research
- Accurate Clinical Research
- Southwest Rheumatology
- Accurate Clinical Management
- NextGen Clinical Research Inc
- Arthiritis & Osteoporosis Centre of South Texas
- Arthritis Clinic Of Central Texas
- Crossroads Clinical Research, LLC
- Arthritis & Osteoporosis Clinic
- South Puget Sound Clinical Research
- Arthritis Northwest, Spokane
- Wenatchee Valley Hospital & Clinics
- Mountain State Clinical Research
- Rheumatic Disease Center
- Lakeshore Orthopedics
- Gundersen Clinic Ltd;Sec. Rheumatology/Dept. of Internal Med
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Non-Randomized Participants (TCZ + MTX)
Randomized Participants (TCZ + MTX)
Randomized Participants (TCZ + PBO)
All participants will receive initial treatment with open-label TCZ + MTX. Participants who complete 24-week treatment with open-label TCZ + MTX and did not achieve a DAS28 score </=3.2 at Week 24, will continue receiving TCZ + MTX in open label manner up to Week 52.
Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score </=3.2 at Week 24, will be randomized to receive TCZ along with MTX up to Week 52.
Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score </=3.2 at Week 24, will be randomized to receive TCZ along with MTX matched placebo (PBO) up to Week 52.