Skip to main content
OpenTrials
Completed

NCT Number: NCT03155347

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

The First Affiliated Hospital of Baotou Medical College, Baotou, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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  • All treatment with non-biological DMARDs except MTX should be withdrawn at least 2 weeks prior to baseline (leflunomide for 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

Treatment and study plan

Tocilizumab

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.

Other names: RO4877533

MTX

Drug

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

Placebo Matched to MTX

Drug

Placebo matched to MTX.

Placebo Matched to Tocilizumab

Drug

Placebo matched to tocilizumab.

Primary outcomes

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

    Time frame: Week 24

Secondary outcomes

  1. 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

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

    Time frame: Week 24

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Week 24

  7. 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

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Week 24

  11. Change From Baseline in DAS28-ESR at Week 24

    Time frame: Baseline, Week 24

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

    Time frame: 56 weeks

  13. 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

  14. Serum Interleukin-6 (IL-6) Levels

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

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

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

  16. Maximum Observed Plasma Concentration (Cmax) of Tocilizumab

    Time frame: predose (Hour 0) and 6-hours postdose on Day 0, Day 84; predose (Hour 0) on Day 14 and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  17. Minimum Observed Plasma Concentration (Cmin) of Tocilizumab

    Time frame: predose (Hour 0) on Day 0, 14, 84, and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  18. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tocilizumab

    Time frame: predose (Hour 0) and 6-hours postdose on Day 0, Day 84; predose (Hour 0) on Day 14 and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  19. Plasma Decay Half-Life (t1/2) of Tocilizumab

    Time frame: predose (Hour 0) and 6-hours postdose on Day 0, Day 84; predose (Hour 0) on Day 14 and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  20. Area Under the Curve from Time Zero to end of dosing interval (AUCtau) of Tocilizumab

    Time frame: predose (Hour 0) and 6-hours postdose on Day 0, Day 84; predose (Hour 0) on Day 14 and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  21. Accumulation Ratio for Area Under the Concentration Time Curve (Rac, AUC) of Tocilizumab

    Time frame: predose (Hour 0) and 6-hours postdose on Day 0, Day 84; predose (Hour 0) on Day 14 and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  22. Accumulation Ratio for Maximum Observed Plasma Concentration (Rac, Cmax) of Tocilizumab

    Time frame: predose (Hour 0) and 6-hours postdose on Day 0, Day 84; predose (Hour 0) on Day 14 and 98; on Day 1, 2, 3, 5, 7, 10, 85, 86, 87, 89, 91, and 94

  23. Accumulation Ratio for Minimum Observed Plasma Trough Concentration (Rac, Cmin) of Tocilizumab

    Time frame: predose (Hour 0) on Day 14, 84

  24. Plasma Trough Concentration (Ctrough) of Tocilizumab

    Time frame: predose (Hour 0) on Day 0, 14, 28, 56, 84, 98, 112, 140, 168, and 336

  25. Percentage of Participants With ACR50 Responses at Week 24

    Time frame: Week 24

  26. Percentage of Participants With ACR70 Responses at Week 24

    Time frame: Week 24

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2022
Study completion
2022
First posted
May 16, 2017
Registry last updated
Nov 28, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.