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

NCT ID: NCT03155347

Last Updated: 2023-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-02

Study Completion Date

2022-08-08

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Tocilizumab + MTX

Participants 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).

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

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.

MTX

Intervention Type DRUG

Participants will receive MTX stable doses at 10 to 25 mg orally.

Tocilizumab + Placebo Matched to MTX

Participants 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.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

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.

MTX

Intervention Type DRUG

Participants will receive MTX stable doses at 10 to 25 mg orally.

Placebo Matched to MTX

Intervention Type DRUG

Placebo matched to MTX.

Placebo Matched to Tocilizumab + MTX

Participants 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.

Group Type ACTIVE_COMPARATOR

Tocilizumab

Intervention Type DRUG

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.

MTX

Intervention Type DRUG

Participants will receive MTX stable doses at 10 to 25 mg orally.

Placebo Matched to Tocilizumab

Intervention Type DRUG

Placebo matched to tocilizumab.

Interventions

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Tocilizumab

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.

Intervention Type DRUG

MTX

Participants will receive MTX stable doses at 10 to 25 mg orally.

Intervention Type DRUG

Placebo Matched to MTX

Placebo matched to MTX.

Intervention Type DRUG

Placebo Matched to Tocilizumab

Placebo matched to tocilizumab.

Intervention Type DRUG

Other Intervention Names

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RO4877533

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The First Affiliated Hospital of Baotou Medical College

Baotou, , China

Site Status

China-Japan Friendship Hospital

Beijing, , China

Site Status

Peking University First Hospital

Beijing, , China

Site Status

Peking University People's Hospital

Beijing, , China

Site Status

Beijing Union Hospital

Beijing, , China

Site Status

Affiliated Hospital of Bengbu Medical College

Bengbu, , China

Site Status

the First Hospital of Jilin University

Changchun, , China

Site Status

West China Hospital, Sichuan University

Chengdu, , China

Site Status

Guangdong General Hospital

Guangzhou, , China

Site Status

The 1st Affiliated Hospital of Harbin Medical University

Harbin, , China

Site Status

The First Affiliated Hospital of Anhui Medical University

Hefei, , China

Site Status

Affiliated Hospital of Inner Mongolia Medical College

Hohhot, , China

Site Status

The First Hospital of Jiaxing

Jiaxing, , China

Site Status

Qilu Hospital of Shandong University

Jinan, , China

Site Status

The First Affilliated Hospital of Kunming Medical College

Kunming, , China

Site Status

Jiangsu Province Hospital

Nanjing, , China

Site Status

Pingxiang People Hospital

Pingxiang, , China

Site Status

Shengjing Hospital of China Medical University

Shenyang, , China

Site Status

The Second Hospital of Shanxi Medical University

Taiyuan, , China

Site Status

Tianjin Medical University General Hospital

Tianjin, , China

Site Status

Countries

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China

References

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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.

Reference Type DERIVED
PMID: 40388166 (View on PubMed)

Other Identifiers

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YA29359

Identifier Type: -

Identifier Source: org_study_id