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CompletedNCT03155347Updated Nov 28, 2023

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 Phase 3 interventional study of Tocilizumab and MTX in Rheumatoid Arthritis, sponsored by Hoffmann-La Roche. Completed at 20 sites in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-11-28.

Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
340
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Rheumatoid Arthritis
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 340 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
340 participants (actual)

Study arms

  • Experimental
    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).

    Drug: Tocilizumab · Drug: MTX

  • Experimental
    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.

    Drug: Tocilizumab · Drug: MTX · Drug: Placebo Matched to MTX

  • Active comparator
    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.

    Drug: Tocilizumab · Drug: MTX · Drug: Placebo Matched to Tocilizumab

Interventions

  • DrugTocilizumab

    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.

    Also known as: RO4877533

  • DrugMTX

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

  • DrugPlacebo Matched to MTX

    Placebo matched to MTX.

  • DrugPlacebo Matched to Tocilizumab

    Placebo matched to tocilizumab.

06

What researchers measure

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

07

Study locations

20 sites
  • The First Affiliated Hospital of Baotou Medical College
    Baotou, 014010, China
  • China-Japan Friendship Hospital
    Beijing City, 100029, China
  • Peking University First Hospital
    Beijing City, 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 City, 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
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 28, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03155347
Lead sponsor
Hoffmann-La Roche
Responsible party
Sponsor
First posted
May 16, 2017
Start date
Aug 2, 2017
Primary completion
Aug 8, 2022
Completion
Aug 8, 2022
Last update
Nov 28, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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