An Efficacy and Safety Study of Subcutaneous Tocilizumab in Combination With Methotrexate (MTX) and as Monotherapy Versus MTX in Participants With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Current Disease-Modifying Antirheumatic Drug (DMARD) Therapy
A Randomized, Multi-Center, Double Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Subcutaneous (SC) Tocilizumab (TCZ) in Combination With Methotrexate (MTX) and as Monotherapy Versus MTX in Patients With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Current DMARD Therapy
1 other identifier
interventional
340
1 country
20
Brief Summary
This is a randomized, double-blind, multi-center, parallel-group study to evaluate the efficacy and safety of subcutaneous (SC) tocilizumab (162 milligrams \[mg\] every 2 weeks \[Q2W\]) given as monotherapy and in combination with MTX versus MTX given as monotherapy, in participants with moderate to severe active rheumatoid arthritis (RA) who have inadequate response to current DMARD therapy. The study comprises a 24-week double-blind treatment phase, followed by a 24-week extension phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 rheumatoid-arthritis
Started Aug 2017
Longer than P75 for phase_3 rheumatoid-arthritis
20 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 15, 2017
CompletedFirst Posted
Study publicly available on registry
May 16, 2017
CompletedStudy Start
First participant enrolled
August 2, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 8, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 8, 2022
CompletedNovember 28, 2023
November 1, 2023
5 years
May 15, 2017
November 27, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With an American College of Rheumatology (ACR) 20 (ACR20) Response at Week 24
Week 24
Secondary Outcomes (26)
Percentage of Participants With Low Disease Activity at Week 24, Defined as Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score of Less Than or Equal to (<=) 3.2
Week 24
Percentage of Participants With Remission at Week 24, Defined as DAS28-ESR Score of Less Than (<) 2.6
Week 24
Change From Baseline in Tender Joint Count (TJC) at Week 24
Baseline, Week 24
Change From Baseline in Swollen Joint Count (SJC) at Week 24
Baseline, Week 24
Change From Baseline in C-reactive Protein (CRP) Levels at Week 24
Baseline, Week 24
- +21 more secondary outcomes
Study Arms (3)
Tocilizumab + MTX
EXPERIMENTALParticipants will receive tocilizumab SC injections Q2W along with MTX orally every week (QW) for 24-week double-blind treatment phase. Participants who complete the 24-week double-blind treatment phase may continue treatment until Week 48 in the extension phase, irrespective if they achieve or do not achieve DAS28 low activity (DAS28-ESR \<= 3.2).
Tocilizumab + Placebo Matched to MTX
EXPERIMENTALParticipants will receive tocilizumab SC Q2W along with placebo matched to MTX for 24-week double-blind treatment phase. Participants who complete the 24-week double-blind treatment phase may continue treatment until Week 48 in the extension phase. In the extension phase up to Week 48, participants who achieve DAS28 low activity (DAS28-ESR \<= 3.2) will remain on the same treatment they received in double-blind phase. Participants who do not achieve DAS28-ESR \<= 3.2 will receive treatment with tocilizumab 162 mg SC Q2W + MTX from Week 26 to Week 48.
Placebo Matched to Tocilizumab + MTX
ACTIVE COMPARATORParticipants will receive placebo matched to tocilizumab along with MTX orally QW for 24-week double-blind treatment phase. Participants who complete the 24-week double-blind treatment phase may continue treatment until Week 48 in the extension phase. In the extension phase up to Week 48, participants who achieve DAS28 low activity (DAS28-ESR \<= 3.2) will remain on the same treatment they received in double-blind phase. Participants who do not achieve DAS28-ESR \<= 3.2 will receive treatment with tocilizumab 162 mg SC Q2W + MTX from Week 26 to Week 48.
Interventions
Participants will receive tocilizumab 162 mg given as 0.9 milliliter (mL) of a 180 mg/mL solution in a prefilled syringe, administered by SC injection Q2W.
Participants will receive MTX stable doses at 10 to 25 mg orally.
Placebo matched to tocilizumab.
Eligibility Criteria
You may qualify if:
- Chinese participants who are located in mainland China with RA of greater than or equal to (\>=) 6 months' duration from onset of the disease, diagnosed according to the revised 1987 ACR criteria and receiving treatment on an outpatient basis
- Participants must have discontinued etanercept (or YiSaiPu) for \>= 2 weeks, infliximab, certolizumab, golimumab, abatacept or adalimumab for \>= 8 weeks, anakinra for \>= 1 week prior to randomization
- Have received oral MTX at a stable dose for at least 12 weeks prior to baseline (MTX dose 10 to 25 mg) and experience of failing at least one non-biologic DMARD including MTX
- All treatment with non-biological DMARDs except MTX should be withdrawn at least 2 weeks prior to baseline (leflunomide for \>= 12 weeks or \>= 14 days after standard cholestyramine or activated charcoal washout, azathioprine for \>= 4 weeks)
- SJC \>= 6 (on the basis of 66 joint counts) and TJC \>= 8 (on the basis of 68 joint counts) at screening and baseline with at least 3 months of treatment with permitted DMARDs
- Participants must have either high sensitive CRP \>= 10 milligrams per liter (mg/L) or ESR \>=28 millimeters per hour (mm/hr) at screening
- Oral corticosteroids (\<=10 mg/day prednisone or equivalent) and nonsteroidal anti-inflammatory drug (NSAIDs; up to the maximum recommended dose per local standard of care) are permitted if the dose has been stable for at least 4 weeks prior to baseline
- All treatment with Chinese traditional medicine and/or herb medicine for RA treatment should be withdrawn at least 2 weeks prior to baseline
- Females of childbearing potential and males with female partners of childbearing potential may participate only if using a reliable means of contraception as defined by the protocol
You may not qualify if:
- Participants with major surgery or planned major surgery, rheumatic autoimmune disease other than RA, and functional class IV (as defined by the ACR Classification of Functional Status in RA)
- Participants with unsuccessful treatment with an anti-tumor necrosis factor (anti-TNF) agent; previous treatment with any cell-depleting therapies including investigational agents and janus kinase (JAK) inhibitors or any other new agents which have DMARD/DMARD-like effect; treatment with intravenous (IV) gamma-globulin, plasmapheresis, or Prosorba column; treatment with alkylating agents
- Intra-articular or parenteral corticosteroids and/or immunization with a live/attenuated vaccine within 4 weeks prior to baseline
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of serious uncontrolled concomitant diseases and disease states; evidence of active malignant disease
- Participants with abnormal haematological parameters, abnormal renal and hepatic parameters
- Positive for either hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and/or hepatitis C virus (HCV) antibody
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
The First Affiliated Hospital of Baotou Medical College
Baotou, 014010, China
China-Japan Friendship Hospital
Beijing, 100029, China
Peking University First Hospital
Beijing, 100034, China
Peking University People's Hospital
Beijing, 100044, China
Beijing Union Hospital
Beijing, 100730, China
Affiliated Hospital of Bengbu Medical College
Bengbu, 233004, China
the First Hospital of Jilin University
Changchun, 130021, China
West China Hospital, Sichuan University
Chengdu, 610041, China
Guangdong General Hospital
Guangzhou, 510080, China
The 1st Affiliated Hospital of Harbin Medical University
Harbin, 150001, China
The First Affiliated Hospital of Anhui Medical University
Hefei, 230022, China
Affiliated Hospital of Inner Mongolia Medical College
Hohhot, 010050, China
The First Hospital of Jiaxing
Jiaxing, 314001, China
Qilu Hospital of Shandong University
Jinan, 250012, China
The First Affilliated Hospital of Kunming Medical College
Kunming, 650032, China
Jiangsu Province Hospital
Nanjing, 210008, China
Pingxiang People Hospital
Pingxiang, 337000, China
Shengjing Hospital of China Medical University
Shenyang, 110004, China
The Second Hospital of Shanxi Medical University
Taiyuan, China
Tianjin Medical University General Hospital
Tianjin, 300052, China
Related Publications (1)
Liu T, Wang L, Zhang X, Chen L, Liu Y, Jiang Z, Shuai Z, Zhang M, Wei W, Liu H, Xu J, Zhang Z, Wang G, Wang X, Hu J, Li H, Zhang Z, Wang H, Lu F, Du Y, Xue Z, Zhao Y, Li Z. Tocilizumab Monotherapy or Combined With Methotrexate for Rheumatoid Arthritis: A Randomized Clinical Trial. JAMA Netw Open. 2025 May 1;8(5):e2511095. doi: 10.1001/jamanetworkopen.2025.11095.
PMID: 40388166DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
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 15, 2017
First Posted
May 16, 2017
Study Start
August 2, 2017
Primary Completion
August 8, 2022
Study Completion
August 8, 2022
Last Updated
November 28, 2023
Record last verified: 2023-11
Data Sharing
- IPD Sharing
- Will not share