A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX
A Randomized, Double-Blind Trial Assessing the Impact of Methotrexate Discontinuation on the Efficacy of Subcutaneous Tocilizumab With Methotrexate Therapy
1 other identifier
interventional
718
1 country
155
Brief Summary
This randomized, multicenter, double-blind, parallel group study will evaluate the impact of MTX discontinuation on the efficacy of SC TCZ in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to current MTX therapy. Participants will initiate treatment with TCZ weekly or every 2 weeks along with MTX at a stable dose orally in an open-label manner for 24 weeks. Participants with a disease activity score based on 28 joints (DAS28) less than or equal to (\</=) 3.2 at Week 24, will be randomized to either continue receiving a stable dose of MTX or to switch to matching placebo up to Week 52. Participants without a DAS28 score \</=3.2 at Week 24, will continue the same treatment in a non-randomized open-label manner up to Week 52.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 rheumatoid-arthritis
Started Nov 2013
Typical duration for phase_3 rheumatoid-arthritis
155 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
First Submitted
Initial submission to the registry
May 14, 2013
CompletedFirst Posted
Study publicly available on registry
May 17, 2013
CompletedStudy Start
First participant enrolled
November 7, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 14, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 14, 2016
CompletedResults Posted
Study results publicly available
December 26, 2017
CompletedDecember 26, 2017
November 1, 2017
2.9 years
May 14, 2013
October 4, 2017
November 30, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40
The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as \[0.56 Ă— square root of TJC\] + \[0.28 Ă— square root of SJC\] + \[0.70 Ă— natural log (ESR)\] + \[0.014 Ă— VAS\]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity.
Week 24, Week 40
Secondary Outcomes (10)
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology (ACR20) Response
Weeks 24, 40, and 52
Percentage of Participants Achieving 50% Improvement in American College of Rheumatology (ACR50) Response
Weeks 24, 40, and 52
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology (ACR70) Response
Weeks 24, 40, and 52
Percentage of Participants With >/=1.2 Points Increase (Worsening) From Week 24 in DAS28 Score at Week 40 and 52
Week 24, 40, and 52
Percentage of Participants With DAS28 Score <2.6 (DAS28 Remission)
Week 40, Week 52
- +5 more secondary outcomes
Study Arms (3)
Non-Randomized Participants (TCZ + MTX)
EXPERIMENTALAll 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.
Randomized Participants (TCZ + MTX)
EXPERIMENTALParticipants 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.
Randomized Participants (TCZ + PBO)
ACTIVE COMPARATORParticipants 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.
Interventions
TCZ will be administered at a dose of 162 milligrams (mg) via SC injection weekly (if body weight is greater than or equal to \[\>/=\] 100 kilograms \[kg\]) or every 2 weeks (if body weight was less than \[\<\] 100 kg).
MTX will be administered at a stable dose (15 mg to 25 mg per week) orally.
PBO matching to MTX will be administered orally.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (155)
Pinnacle Research Group; Llc, Central
Anniston, Alabama, 36207, United States
Uni Of Alabama,Birmingham; Medicine - Rheumatology
Birmingham, Alabama, 35294, United States
Rheumatology Associates of North Alabama
Huntsville, Alabama, 35801, United States
Clnical & Translational Reseach Center for Alabama, PC
Tuscaloosa, Alabama, 35406, United States
Arizona Arthritis & Rheumatology Associates, P.C.
Glendale, Arizona, 85306, United States
Arizona Arthritis & Rheumatology Research, Pllc
Mesa, Arizona, 85202, United States
Arizona Arthritis and Rheuma
Mesa, Arizona, 85202, United States
Valley Arthritis Care
Phoenix, Arizona, 85027, United States
Advanced Arthritis Care & Research
Scottsdale, Arizona, 85258, United States
Fort Smith Rheumatology, PC
Fort Smith, Arkansas, 72903, United States
CHI St. Vincent Medical Group Hot Springs
Hot Springs, Arkansas, 71913, United States
NEA Baptist Clinic
Jonesboro, Arkansas, 72401, United States
Little Rock Diagnostic Clinic
Little Rock, Arkansas, 72205, United States
Medvin Clinical Research
Covina, California, 91723, United States
TriWest Research Associates, LLC
El Cajon, California, 92020, United States
St. Jude Hospital Yorba Linda DBA St. Joseph
Fullerton, California, 92835, United States
CV Mehta MD Medical Corp
Hemet, California, 92543, United States
Valerius Medical Group
Los Alamitos, California, 90720, United States
NRC Research Institute
Orange, California, 92868, United States
San Diego Arthritis Med Clnc
San Diego, California, 92108, United States
C Michael Neuwelt MD Inc
San Leandro, California, 94578, United States
Inland Rheumatology; Clinical Trials, Inc.
Upland, California, 91785-1141, United States
Medvin Clinical Research
Whittier, California, 90606, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs
Colorado Springs, Colorado, 80920, United States
Denver Arthritis Clinic
Denver, Colorado, 80230-7127, United States
Joao Nascimento
Bridgeport, Connecticut, 06606, United States
Clinical Research Center of Ct/Ny
Danbury, Connecticut, 06810, United States
Arthritis & Osteoporosis Center Pc
Hamden, Connecticut, 06518, United States
New England Research Associates
Trumbull, Connecticut, 06611, United States
Rheumatolgy Consultants of Deleware
Lewes, Delaware, 19958, United States
Javed Rheumatology Associates, Inc.
Newark, Delaware, 19713, United States
Arthritis & Rheumatism; Disease Specialities
Aventura, Florida, 33180, United States
Robert Levin, Md; Research Dept
Dunedin, Florida, 34698, United States
Suncoast Research Group LLC
Miami, Florida, 33135, United States
South Coast Research Center, Inc.
Miami, Florida, 33136, United States
Precision Research Organization
Miami Lakes, Florida, 33016, United States
Jeffrey Alper M.D Research
Naples, Florida, 34102, United States
Rheumatology Associates of Central Florida
Orlando, Florida, 32806, United States
Arthritis and Rheumatology Clinic
Orlando, Florida, 32836, United States
Arthritis Center Palm Harbor
Palm Harbor, Florida, 34684, United States
Arthritis Rsrch of Florida, Inc.
Palm Harbor, Florida, 34684, United States
Sarasota Arthritis Res Center
Sarasota, Florida, 34239, United States
Pinellas Medical Research - Allegry & Rheumatology Associates, LLC
St. Petersburg, Florida, 33708, United States
West Broward Rheumatology Associates, Inc.
Tamarac, Florida, 33321, United States
McIlwain Medical Group
Tampa, Florida, 33613, United States
Burnette & Silverfield, MDS
Tampa, Florida, 33614, United States
Advanced Clinical Research of Orlando, Inc.
Winter Garden, Florida, 34787, United States
North Georgia Rheumatology
Duluth, Georgia, 30096, United States
Arthritis Center of North Georgia
Gainesville, Georgia, 30501, United States
North Georgia Rheumatology Group, PC
Lawrenceville, Georgia, 30046, United States
Institute of Arthritis Research
Idaho Falls, Idaho, 83404, United States
Springfield Clinic
Springfield, Illinois, 62703, United States
Indiana Uni Medical Center
Indianapolis, Indiana, 46202, United States
Diagnostic Rheumatology & Research
Indianapolis, Indiana, 46227, United States
Kansas City Internal Medicine
Overland Park, Kansas, 66209, United States
Bluegrass Comm Research, Inc.
Lexington, Kentucky, 40515, United States
Arthritis & Diabetes Clinic, Inc
Monroe, Louisiana, 71203, United States
Klein & Associates, M.D., P.A.
Hagerstown, Maryland, 21740, United States
New England Medical Center; Dept. of Medicine, Div. of Rheumatology
Boston, Massachusetts, 02111, United States
Phase Iii Clinical Research
Fall River, Massachusetts, 02720, United States
Mansfield Medical Center
Mansfield, Massachusetts, 02048, United States
Reliant Medical Group, Inc; Rheumatology
Worcester, Massachusetts, 01605, United States
UMass Memorial Medical Center
Worcester, Massachusetts, 01605, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01610, United States
Advanced Rheumatology, PC
Lansing, Michigan, 48910, United States
Fiechtner Research Inc
Lansing, Michigan, 48910, United States
Nisus Research/Northern Michigan Hospital
Petoskey, Michigan, 49770, United States
Shores Rheumatology
Saint Clair Shores, Michigan, 48081, United States
St. Luke's Hospital Association of Duluth
Duluth, Minnesota, 55805, United States
St. Paul Rheumatology
Eagan, Minnesota, 55121, United States
Arthritis and Osteoporosis; Treatment and Research Center
Flowood, Mississippi, 39232, United States
Jackson Arthritis Clinic
Flowood, Mississippi, 39232, United States
David S Rosenberg
Florissant, Missouri, 63031, United States
Clinical Research Consultants,LLC
Kansas City, Missouri, 64111, United States
Clayton Medical Research
St Louis, Missouri, 63117, United States
Arthritis Consultants
St Louis, Missouri, 63141, United States
G. T. Kelly, MD
Las Vegas, Nevada, 89128, United States
Rheumatology Research Group
Lebanon, New Hampshire, 03756, United States
Nashua Rheumatology - Foundation Medical Partners
Nashua, New Hampshire, 03060, United States
Arthritis and Osteoporosis Associates
Manalapan, New Jersey, 07726, United States
Atlantic Coast Rheumatology
Toms River, New Jersey, 08755, United States
Ocean Rheumatology
Toms River, New Jersey, 08775, United States
Arthritis Rheumatic & Back Disease Associates
Voorhees Township, New Jersey, 08043, United States
Cooper Cancer Institute
Voorhees Township, New Jersey, 08043, United States
Albuquerque Clinical Trials
Albuquerque, New Mexico, 87102, United States
Arthritis and Osteoporosis Associates of New Mexico
Las Cruces, New Mexico, 88011, United States
The Center for Rheumatology
Albany, New York, 12203, United States
Arthritis & Osteoporosis Center
Brooklyn, New York, 11201, United States
Manhasset Rheumatology
Manhasset, New York, 11030, United States
Manhattan Medical Reserach
New York, New York, 10016, United States
Buffalo Rheumatology Associates
Orchard Park, New York, 14127, United States
Office of Premier Chatpar Md
Plainview, New York, 11803, United States
Rheumatology Associates of Long Island
Smithtown, New York, 11787, United States
Arthritis Health Associates
Syracuse, New York, 13210, United States
Asheville Arthritis & Osteoporosis Center, PA
Asheville, North Carolina, 28803, United States
Carolina Bone & Joint P.A.
Charlotte, North Carolina, 28210, United States
Triangle Orthopaedics Associates, P.A.
Durham, North Carolina, 27704, United States
Medication Management
Greensboro, North Carolina, 27408, United States
PMG Research of Hickory LLC
Hickory, North Carolina, 28602, United States
Cape Fear Arthritis Care
Leland, North Carolina, 28451, United States
Shanahan Rheumatology & Immunology, PLLC
Raleigh, North Carolina, 27617, United States
St. Alexius Medical Center; Arthritis Clinic
Bismarck, North Dakota, 58501, United States
Odyssey Research Services; Main Medical Building
Bismarck, North Dakota, 58507, United States
Crystal Arthritis Center, Inc.
Akron, Ohio, 44333, United States
Cincinnati Rheumatic Disease Study Group
Cincinnati, Ohio, 45219, United States
University Hospitals Case Medical Center
Cleveland, Ohio, 44109, United States
Ohio State University; Rheumatology; Immun/Rheum
Columbus, Ohio, 43203, United States
Columbus Arthritis Center
Columbus, Ohio, 43215, United States
STAT Research Inc
Dayton, Ohio, 45417, United States
Paramount Medical Research
Middleburg Heights, Ohio, 44130, United States
Clinical Research Source, Inc.
Toledo, Ohio, 43606, United States
Arthritis Care Center Oklahoma
Ardmore, Oklahoma, 73401, United States
Arthritis and Rheumatology; Center of Oklahoma PLLC
Oklahoma City, Oklahoma, 73103, United States
Health Research of Oklahoma, Llc
Oklahoma City, Oklahoma, 73103, United States
Lynn Health Science Inst.
Oklahoma City, Oklahoma, 73112, United States
Oklahoma Center For Arthritis Therapy & Research
Tulsa, Oklahoma, 74104, United States
Healthcare Research Consultants
Tulsa, Oklahoma, 74135, United States
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635, United States
Arthritis Associates
Erie, Pennsylvania, 16508, United States
Arthritis Group
Philadelphia, Pennsylvania, 19152, United States
Advanced Rheumatology & Arthritis Research Center
Wexford, Pennsylvania, 15090, United States
Clinical Research Center of Reading
Wyomissing, Pennsylvania, 19610, United States
Emkey Arthritis & Osteoporosis
Wyomissing, Pennsylvania, 19610, United States
Low Country Rheumatology, PA
Charleston, South Carolina, 29406, United States
Columbia Arthritis Center (Partnership Practice)
Columbia, South Carolina, 29204, United States
Piedmont Arthritis Clinic
Greenville, South Carolina, 29601, United States
West Tennessee Research Institute
Jackson, Tennessee, 38305, United States
Ramesh Gupta - PP
Memphis, Tennessee, 38119, United States
Amarillo Center For Clinical Research
Amarillo, Texas, 79124, United States
Austin Regional Clinic
Austin, Texas, 78731, United States
Lovelace Scientific Resources Inc.
Austin, Texas, 78758, United States
Diagnostic Group
Beaumont, Texas, 77701, United States
AOCBV
College Station, Texas, 77845, United States
Adriana Pop-Moody MD Clinic PA
Corpus Christi, Texas, 78404, United States
Arthritis Care & Diagnostic Center
Dallas, Texas, 75231-4406, United States
Metroplex Clinical Research
Dallas, Texas, 75231, United States
Rheumatic Disease Clin Res Ctr
Houston, Texas, 77004, United States
IntraFusion Researh Network
Houston, Texas, 77007, United States
Houston Inst. For Clinical Research
Houston, Texas, 77074, United States
Accurate Clinical Research
Houston, Texas, 77089, United States
Southwest Rheumatology
Mesquite, Texas, 75150, United States
Accurate Clinical Management
San Antonio, Texas, 78229, United States
NextGen Clinical Research Inc
San Antonio, Texas, 78229, United States
Arthiritis & Osteoporosis Centre of South Texas
San Antonio, Texas, 78232, United States
Arthritis Clinic Of Central Texas
San Marcos, Texas, 78666, United States
Crossroads Clinical Research, LLC
Victoria, Texas, 77901, United States
Arthritis & Osteoporosis Clinic
Waco, Texas, 76710, United States
South Puget Sound Clinical Research
Olympia, Washington, 98502, United States
Arthritis Northwest, Spokane
Spokane, Washington, 99204, United States
Wenatchee Valley Hospital & Clinics
Wenatchee, Washington, 98801, United States
Mountain State Clinical Research
Clarksburg, West Virginia, 26301, United States
Rheumatic Disease Center
Glendale, Wisconsin, 53217, United States
Lakeshore Orthopedics
Manitowoc, Wisconsin, 54220, United States
Gundersen Clinic Ltd;Sec. Rheumatology/Dept. of Internal Med
Onalaska, Wisconsin, 54605, United States
Related Publications (1)
Kremer JM, Rigby W, Singer NG, Birchwood C, Gill D, Reiss W, Pei J, Michalska M. Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a Randomized, Controlled Trial. Arthritis Rheumatol. 2018 Aug;70(8):1200-1208. doi: 10.1002/art.40493. Epub 2018 Jun 14.
PMID: 29575803DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
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
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2013
First Posted
May 17, 2013
Study Start
November 7, 2013
Primary Completion
October 14, 2016
Study Completion
October 14, 2016
Last Updated
December 26, 2017
Results First Posted
December 26, 2017
Record last verified: 2017-11