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

Hoffmann-La Roche340 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

340

Conditions

Rheumatoid Arthritis

Interventions

Tocilizumab

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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failing at least one non-biologic DMARD including MTX * All treatment with non-biological DMARDs except MTX should be withdrawn at least 2 weeks prior to baseline (leflunomide for \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 Exclusion Criteria: * 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

Locations (20)

The First Affiliated Hospital of Baotou Medical College

Baotou, China

China-Japan Friendship Hospital

Beijing, China

Peking University First Hospital

Beijing, China

Peking University People's Hospital

Beijing, China

Beijing Union Hospital

Beijing, China

Affiliated Hospital of Bengbu Medical College

Bengbu, China

the First Hospital of Jilin University

Changchun, China

West China Hospital, Sichuan University

Chengdu, China

Guangdong General Hospital

Guangzhou, China

The 1st Affiliated Hospital of Harbin Medical University

Harbin, China

...and 10 more locations

Outcomes

Primary Outcomes

Percentage of Participants With an American College of Rheumatology (ACR) 20 (ACR20) Response at Week 24

Time frame: Week 24

Secondary Outcomes

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

Time frame: Week 24

Percentage of Participants With Remission at Week 24, Defined as DAS28-ESR Score of Less Than (<) 2.6

Time frame: Week 24

Change From Baseline in Tender Joint Count (TJC) at Week 24

Time frame: Baseline, Week 24

Change From Baseline in Swollen Joint Count (SJC) at Week 24

Time frame: Baseline, Week 24

Change From Baseline in C-reactive Protein (CRP) Levels at Week 24

Time frame: Baseline, Week 24

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24

Time frame: Baseline, Week 24

Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score at Week 24

Time frame: Baseline, Week 24

Change From Baseline in the Physician's Global Assessment of Disease Activity VAS Score at Week 24

Time frame: Baseline, Week 24

Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24

Time frame: Baseline, Week 24

Change From Baseline in the Patient's Pain VAS at Week 24

Time frame: Baseline, Week 24

Change From Baseline in DAS28-ESR at Week 24

Time frame: Baseline, Week 24

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: 56 weeks

Percentage of Participants With anti-Tocilizumab Antibody

Time frame: Baseline, Week 12, Week 24, Week 48, at the time of withdrawal up to approximately 48 weeks

Serum Interleukin-6 (IL-6) Levels

Time frame: Baseline, predose (Hour 0) on Weeks 2, 4, 8, 12, 16, 24, 48

Serum Soluble Interleukin-6 Receptor (sIL-6R) Levels

Time frame: Baseline, predose (Hour 0) on Weeks 2, 4, 8, 12, 16, 24, 48

Maximum Observed Plasma Concentration (Cmax) of Tocilizumab