Rheumatoid ArthritisPhase 3NCT01855789
A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX
A Phase 3 study testing Tocilizumab (TCZ) and Methotrexate (MTX) in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 155 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Tocilizumab (TCZ) and Methotrexate (MTX)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 718 participants
- Where
- 155 sitesUnited States
- Study dates
- 7 Nov 2013to 14 Oct 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
155 sites in 1 country.
155 sites in 1 country
United States155 sites
Crystal Arthritis Center, Inc.
Akron, Ohio, 44333
The Center for Rheumatology
Albany, New York, 12203
Albuquerque Clinical Trials
Albuquerque, New Mexico, 87102
Amarillo Center For Clinical Research
Amarillo, Texas, 79124
Pinnacle Research Group; Llc, Central
Anniston, Alabama, 36207
Arthritis Care Center Oklahoma
Ardmore, Oklahoma, 73401
Asheville Arthritis & Osteoporosis Center, PA
Asheville, North Carolina, 28803
University of Colorado Hospital
Aurora, Colorado, 80045
Austin Regional Clinic
Austin, Texas, 78731
Lovelace Scientific Resources Inc.
Austin, Texas, 78758
Arthritis & Rheumatism; Disease Specialities
Aventura, Florida, 33180
Diagnostic Group
Beaumont, Texas, 77701
Uni Of Alabama,Birmingham; Medicine - Rheumatology
Birmingham, Alabama, 35294
St. Alexius Medical Center; Arthritis Clinic
Bismarck, North Dakota, 58501
Odyssey Research Services; Main Medical Building
Bismarck, North Dakota, 58507
New England Medical Center; Dept. of Medicine, Div. of Rheumatology
Boston, Massachusetts, 02111
Joao Nascimento
Bridgeport, Connecticut, 06606
Arthritis & Osteoporosis Center
Brooklyn, New York, 11201
Low Country Rheumatology, PA
Charleston, South Carolina, 29406
Carolina Bone & Joint P.A.
Charlotte, North Carolina, 28210
Cincinnati Rheumatic Disease Study Group
Cincinnati, Ohio, 45219
Mountain State Clinical Research
Clarksburg, West Virginia, 26301
University Hospitals Case Medical Center
Cleveland, Ohio, 44109
AOCBV
College Station, Texas, 77845
Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs
Colorado Springs, Colorado, 80920
Columbia Arthritis Center (Partnership Practice)
Columbia, South Carolina, 29204
Ohio State University; Rheumatology; Immun/Rheum
Columbus, Ohio, 43203
Columbus Arthritis Center
Columbus, Ohio, 43215
Adriana Pop-Moody MD Clinic PA
Corpus Christi, Texas, 78404
Medvin Clinical Research
Covina, California, 91723
Arthritis Care & Diagnostic Center
Dallas, Texas, 75231-4406
Metroplex Clinical Research
Dallas, Texas, 75231
Clinical Research Center of Ct/Ny
Danbury, Connecticut, 06810
STAT Research Inc
Dayton, Ohio, 45417
Denver Arthritis Clinic
Denver, Colorado, 80230-7127
North Georgia Rheumatology
Duluth, Georgia, 30096
St. Luke's Hospital Association of Duluth
Duluth, Minnesota, 55805
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635
Robert Levin, Md; Research Dept
Dunedin, Florida, 34698
Triangle Orthopaedics Associates, P.A.
Durham, North Carolina, 27704
St. Paul Rheumatology
Eagan, Minnesota, 55121
TriWest Research Associates, LLC
El Cajon, California, 92020
Arthritis Associates
Erie, Pennsylvania, 16508
Phase Iii Clinical Research
Fall River, Massachusetts, 02720
David S Rosenberg
Florissant, Missouri, 63031
Arthritis and Osteoporosis; Treatment and Research Center
Flowood, Mississippi, 39232
Jackson Arthritis Clinic
Flowood, Mississippi, 39232
Fort Smith Rheumatology, PC
Fort Smith, Arkansas, 72903
St. Jude Hospital Yorba Linda DBA St. Joseph
Fullerton, California, 92835
Arthritis Center of North Georgia
Gainesville, Georgia, 30501
Arizona Arthritis & Rheumatology Associates, P.C.
Glendale, Arizona, 85306
Rheumatic Disease Center
Glendale, Wisconsin, 53217
Medication Management
Greensboro, North Carolina, 27408
Piedmont Arthritis Clinic
Greenville, South Carolina, 29601
Klein & Associates, M.D., P.A.
Hagerstown, Maryland, 21740
Arthritis & Osteoporosis Center Pc
Hamden, Connecticut, 06518
CV Mehta MD Medical Corp
Hemet, California, 92543
PMG Research of Hickory LLC
Hickory, North Carolina, 28602
CHI St. Vincent Medical Group Hot Springs
Hot Springs, Arkansas, 71913
Rheumatic Disease Clin Res Ctr
Houston, Texas, 77004
IntraFusion Researh Network
Houston, Texas, 77007
Houston Inst. For Clinical Research
Houston, Texas, 77074
Accurate Clinical Research
Houston, Texas, 77089
Rheumatology Associates of North Alabama
Huntsville, Alabama, 35801
Institute of Arthritis Research
Idaho Falls, Idaho, 83404
Indiana Uni Medical Center
Indianapolis, Indiana, 46202
Diagnostic Rheumatology & Research
Indianapolis, Indiana, 46227
West Tennessee Research Institute
Jackson, Tennessee, 38305
NEA Baptist Clinic
Jonesboro, Arkansas, 72401
Clinical Research Consultants,LLC
Kansas City, Missouri, 64111
Advanced Rheumatology, PC
Lansing, Michigan, 48910
Fiechtner Research Inc
Lansing, Michigan, 48910
Arthritis and Osteoporosis Associates of New Mexico
Las Cruces, New Mexico, 88011
G. T. Kelly, MD
Las Vegas, Nevada, 89128
North Georgia Rheumatology Group, PC
Lawrenceville, Georgia, 30046
Rheumatology Research Group
Lebanon, New Hampshire, 03756
Cape Fear Arthritis Care
Leland, North Carolina, 28451
Rheumatolgy Consultants of Deleware
Lewes, Delaware, 19958
Bluegrass Comm Research, Inc.
Lexington, Kentucky, 40515
Little Rock Diagnostic Clinic
Little Rock, Arkansas, 72205
Valerius Medical Group
Los Alamitos, California, 90720
Arthritis and Osteoporosis Associates
Manalapan, New Jersey, 07726
Manhasset Rheumatology
Manhasset, New York, 11030
Lakeshore Orthopedics
Manitowoc, Wisconsin, 54220
Mansfield Medical Center
Mansfield, Massachusetts, 02048
Ramesh Gupta - PP
Memphis, Tennessee, 38119
Arizona Arthritis & Rheumatology Research, Pllc
Mesa, Arizona, 85202
Arizona Arthritis and Rheuma
Mesa, Arizona, 85202
Southwest Rheumatology
Mesquite, Texas, 75150
Suncoast Research Group LLC
Miami, Florida, 33135
South Coast Research Center, Inc.
Miami, Florida, 33136
Precision Research Organization
Miami Lakes, Florida, 33016
Paramount Medical Research
Middleburg Heights, Ohio, 44130
Arthritis & Diabetes Clinic, Inc
Monroe, Louisiana, 71203
Jeffrey Alper M.D Research
Naples, Florida, 34102
Nashua Rheumatology - Foundation Medical Partners
Nashua, New Hampshire, 03060
Manhattan Medical Reserach
New York, New York, 10016
Javed Rheumatology Associates, Inc.
Newark, Delaware, 19713
Arthritis and Rheumatology; Center of Oklahoma PLLC
Oklahoma City, Oklahoma, 73103
Health Research of Oklahoma, Llc
Oklahoma City, Oklahoma, 73103
Lynn Health Science Inst.
Oklahoma City, Oklahoma, 73112
South Puget Sound Clinical Research
Olympia, Washington, 98502
Gundersen Clinic Ltd;Sec. Rheumatology/Dept. of Internal Med
Onalaska, Wisconsin, 54605
NRC Research Institute
Orange, California, 92868
Buffalo Rheumatology Associates
Orchard Park, New York, 14127
Rheumatology Associates of Central Florida
Orlando, Florida, 32806
Arthritis and Rheumatology Clinic
Orlando, Florida, 32836
Kansas City Internal Medicine
Overland Park, Kansas, 66209
Arthritis Center Palm Harbor
Palm Harbor, Florida, 34684
Arthritis Rsrch of Florida, Inc.
Palm Harbor, Florida, 34684
Nisus Research/Northern Michigan Hospital
Petoskey, Michigan, 49770
Arthritis Group
Philadelphia, Pennsylvania, 19152
Valley Arthritis Care
Phoenix, Arizona, 85027
Office of Premier Chatpar Md
Plainview, New York, 11803
Shanahan Rheumatology & Immunology, PLLC
Raleigh, North Carolina, 27617
Shores Rheumatology
Saint Clair Shores, Michigan, 48081
Accurate Clinical Management
San Antonio, Texas, 78229
NextGen Clinical Research Inc
San Antonio, Texas, 78229
Arthiritis & Osteoporosis Centre of South Texas
San Antonio, Texas, 78232
San Diego Arthritis Med Clnc
San Diego, California, 92108
C Michael Neuwelt MD Inc
San Leandro, California, 94578
Arthritis Clinic Of Central Texas
San Marcos, Texas, 78666
Sarasota Arthritis Res Center
Sarasota, Florida, 34239
Advanced Arthritis Care & Research
Scottsdale, Arizona, 85258
Rheumatology Associates of Long Island
Smithtown, New York, 11787
Arthritis Northwest, Spokane
Spokane, Washington, 99204
Springfield Clinic
Springfield, Illinois, 62703
Clayton Medical Research
St Louis, Missouri, 63117
Arthritis Consultants
St Louis, Missouri, 63141
Pinellas Medical Research - Allegry & Rheumatology Associates, LLC
St. Petersburg, Florida, 33708
Arthritis Health Associates
Syracuse, New York, 13210
West Broward Rheumatology Associates, Inc.
Tamarac, Florida, 33321
McIlwain Medical Group
Tampa, Florida, 33613
Burnette & Silverfield, MDS
Tampa, Florida, 33614
Clinical Research Source, Inc.
Toledo, Ohio, 43606
Atlantic Coast Rheumatology
Toms River, New Jersey, 08755
Ocean Rheumatology
Toms River, New Jersey, 08775
New England Research Associates
Trumbull, Connecticut, 06611
Oklahoma Center For Arthritis Therapy & Research
Tulsa, Oklahoma, 74104
Healthcare Research Consultants
Tulsa, Oklahoma, 74135
Clnical & Translational Reseach Center for Alabama, PC
Tuscaloosa, Alabama, 35406
Inland Rheumatology; Clinical Trials, Inc.
Upland, California, 91785-1141
Crossroads Clinical Research, LLC
Victoria, Texas, 77901
Arthritis Rheumatic & Back Disease Associates
Voorhees Township, New Jersey, 08043
Cooper Cancer Institute
Voorhees Township, New Jersey, 08043
Arthritis & Osteoporosis Clinic
Waco, Texas, 76710
Wenatchee Valley Hospital & Clinics
Wenatchee, Washington, 98801
Advanced Rheumatology & Arthritis Research Center
Wexford, Pennsylvania, 15090
Medvin Clinical Research
Whittier, California, 90606
Advanced Clinical Research of Orlando, Inc.
Winter Garden, Florida, 34787
Reliant Medical Group, Inc; Rheumatology
Worcester, Massachusetts, 01605
UMass Memorial Medical Center
Worcester, Massachusetts, 01605
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01610
Clinical Research Center of Reading
Wyomissing, Pennsylvania, 19610
Emkey Arthritis & Osteoporosis
Wyomissing, Pennsylvania, 19610
About this study
Official title: A Randomized, Double-Blind Trial Assessing the Impact of Methotrexate Discontinuation on the Efficacy of Subcutaneous Tocilizumab With Methotrexate Therapy
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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Tocilizumab (TCZ), Methotrexate (MTX), Placebo (PBO)
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tocilizumab (TCZ)Drug
Also called Actemra
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).
Methotrexate (MTX)Drug
MTX will be administered at a stable dose (15 mg to 25 mg per week) orally.
Placebo (PBO)Drug
PBO matching to MTX will be administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Non-Randomized Participants (TCZ + MTX) | Experimental | 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. Receives: Drug: Tocilizumab (TCZ); Drug: Methotrexate (MTX) |
| Randomized Participants (TCZ + MTX) | Experimental | 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. Receives: Drug: Tocilizumab (TCZ); Drug: Methotrexate (MTX) |
| Randomized Participants (TCZ + PBO) | Active comparator | 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. Receives: Drug: Tocilizumab (TCZ); Drug: Placebo (PBO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × 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.
Measured: Week 24, Week 40
Secondary outcomes (10)
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology (ACR20) Response
The ACR20 response at any time was defined as >/=20% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via a Health Assessment Questionnaire-Disability Index (HAQ-DI), and 5) Acute phase reactant (ESR in mm/h or C-Reactive Protein [CRP] in milligrams per deciliter [mg/dL]).
Measured: Weeks 24, 40, and 52
Percentage of Participants Achieving 50% Improvement in American College of Rheumatology (ACR50) Response
The ACR50 response at any time was defined as >/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).
Measured: Weeks 24, 40, and 52
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology (ACR70) Response
The ACR70 response at any time was defined as >/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).
Measured: 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
The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28- score could range from 0 to 10, where higher score represented higher disease activity.
Measured: Week 24, 40, and 52
Percentage of Participants With DAS28 Score <2.6 (DAS28 Remission)
The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity.
Measured: Week 40, Week 52
Percentage of Participants With DAS28 Score </=3.2 (Low DAS28)
The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28-ESR score could range from 0 to 10, where higher score represented higher disease activity.
Measured: Week 40, Week 52
Change From Week 24 in Bone Erosion Score at Week 40 for Participants in the Magnetic Resonance Imaging (MRI) Substudy
Bones from the wrist regions (carpal bones, distal radius, distal ulna, and metacarpal bases) and the metacarpophalangeal (MCP) joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranged from 0 (no erosion) to 10 (91-100%). Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value for change from Week 24 in bone erosion score indicated an improvement.
Measured: Weeks 24, Week 40
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TCZ
Percentage of participants with positive results for ATA against TCZ at Baseline and at any of the post-baseline assessment time-points was reported. Participants positive at any post-baseline time points were participants who had no positivity at baseline for the same assay.
Measured: Baseline, Post-baseline (assessed at Weeks 12, 24, 36, 52 and at follow up [Week 60])
Mean TCZ Serum Concentration
Measured: Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)
Mean Soluble Interleukin-6 (IL-6) Receptor Concentration
Measured: Baseline, Weeks 12, 24, 36, 52 and follow up (Week 60)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2013 (estimated)
- Study start7 Nov 2013
- Primary completion14 Oct 2016
- Study completion14 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 718 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01855789
- Sponsor's protocol ID
- ML28776
- Status last verified
- Nov 2017
- First submitted
- 14 May 2013
- Last updated
- 26 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 29575803
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Trial Assessing the Impact of Methotrexate Discontinuation on the Efficacy of Subcutaneous Tocilizumab With Methotrexate Therapy
- ClinicalTrials.gov ID
- NCT01855789
- Acronym / sponsor ID
- ML28776
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 718 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2013 (actual)
- Primary completion
- 14 Oct 2016 (actual)
- Study completion
- 14 Oct 2016 (actual)
- First posted
- 17 May 2013 (estimated)
- Results
- Posted 26 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Non-Randomized Participants (TCZ + MTX) | Experimental | Drug: Tocilizumab (TCZ), Drug: Methotrexate (MTX)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. |
| Randomized Participants (TCZ + MTX) | Experimental | Drug: Tocilizumab (TCZ), Drug: Methotrexate (MTX)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. |
| Randomized Participants (TCZ + PBO) | Active comparator | Drug: Tocilizumab (TCZ), Drug: Placebo (PBO)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tocilizumab (TCZ)Also: ActemraTCZ 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). | Drug | Non-Randomized Participants (TCZ + MTX), Randomized Participants (TCZ + MTX), Randomized Participants (TCZ + PBO) |
| Methotrexate (MTX)MTX will be administered at a stable dose (15 mg to 25 mg per week) orally. | Drug | Non-Randomized Participants (TCZ + MTX), Randomized Participants (TCZ + MTX) |
| Placebo (PBO)PBO matching to MTX will be administered orally. | Drug | Randomized Participants (TCZ + PBO) |
Primary outcome
Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40
Time frame: Week 24, 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 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × 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.
10 secondary outcomes
Percentage of Participants Achieving 20% Improvement in American College of Rheumatology (ACR20) Response
Time frame: Weeks 24, 40, and 52
Percentage of Participants Achieving 50% Improvement in American College of Rheumatology (ACR50) Response
Time frame: Weeks 24, 40, and 52
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology (ACR70) Response
Time frame: 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
Time frame: Week 24, 40, and 52
Percentage of Participants With DAS28 Score <2.6 (DAS28 Remission)
Time frame: Week 40, Week 52
Percentage of Participants With DAS28 Score </=3.2 (Low DAS28)
Time frame: Week 40, Week 52
Change From Week 24 in Bone Erosion Score at Week 40 for Participants in the Magnetic Resonance Imaging (MRI) Substudy
Time frame: Weeks 24, Week 40
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TCZ
Time frame: Baseline, Post-baseline (assessed at Weeks 12, 24, 36, 52 and at follow up [Week 60])
Mean TCZ Serum 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29575803Kremer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
155 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tocilizumab (TCZ) and Methotrexate (MTX) in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 155 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 155 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40 (time frame: Week 24, Week 40). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01855789, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2017.