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Rheumatoid ArthritisPhase 3NCT03155347

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 study testing Tocilizumab and MTX in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 20 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Tocilizumab and MTX
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
340 participants
Where
20 sitesChina
Study dates
2 Aug 2017to 8 Aug 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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  • All treatment with non-biological DMARDs except MTX should be withdrawn at least 2 weeks prior to baseline (leflunomide for 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

Who cannot join

  • 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

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

China20 sites

  • The First Affiliated Hospital of Baotou Medical College

    Baotou, 014010

  • China-Japan Friendship Hospital

    Beijing, 100029

  • Peking University First Hospital

    Beijing, 100034

  • Peking University People's Hospital

    Beijing, 100044

  • Beijing Union Hospital

    Beijing, 100730

  • Affiliated Hospital of Bengbu Medical College

    Bengbu, 233004

  • the First Hospital of Jilin University

    Changchun, 130021

  • West China Hospital, Sichuan University

    Chengdu, 610041

  • Guangdong General Hospital

    Guangzhou, 510080

  • The 1st Affiliated Hospital of Harbin Medical University

    Harbin, 150001

  • The First Affiliated Hospital of Anhui Medical University

    Hefei, 230022

  • Affiliated Hospital of Inner Mongolia Medical College

    Hohhot, 010050

  • The First Hospital of Jiaxing

    Jiaxing, 314001

  • Qilu Hospital of Shandong University

    Jinan, 250012

  • The First Affilliated Hospital of Kunming Medical College

    Kunming, 650032

  • Jiangsu Province Hospital

    Nanjing, 210008

  • Pingxiang People Hospital

    Pingxiang, 337000

  • Shengjing Hospital of China Medical University

    Shenyang, 110004

  • The Second Hospital of Shanxi Medical University

    Taiyuan

  • Tianjin Medical University General Hospital

    Tianjin, 300052

Other trials in China

About this study

Official 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

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.

Being tested
Tocilizumab, MTX, Placebo Matched to MTX, Placebo Matched to Tocilizumab
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TocilizumabDrug

    Also called RO4877533

    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.

  • MTXDrug

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

  • Placebo Matched to MTXDrug

    Placebo matched to MTX.

  • Placebo Matched to TocilizumabDrug

    Placebo matched to tocilizumab.

Study groups in NCT03155347
Study groupRoleWhat they receive
Tocilizumab + MTXExperimentalParticipants 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).
Receives: Drug: Tocilizumab; Drug: MTX
Tocilizumab + Placebo Matched to MTXExperimentalParticipants 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.
Receives: Drug: Tocilizumab; Drug: MTX; Drug: Placebo Matched to MTX
Placebo Matched to Tocilizumab + MTXActive 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.
Receives: Drug: Tocilizumab; Drug: MTX; Drug: Placebo Matched to Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Week 24

Secondary outcomes (26)

  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

    Measured: Week 24

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

    Measured: Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: Baseline, Week 24

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

    Measured: 56 weeks

  13. Percentage of Participants With anti-Tocilizumab Antibody

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

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

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

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

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

  16. Maximum Observed Plasma Concentration (Cmax) of Tocilizumab

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: predose (Hour 0) on Day 14, 84

  24. Plasma Trough Concentration (Ctrough) of Tocilizumab

    Measured: 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

    Measured: Week 24

  26. Percentage of Participants With ACR70 Responses at Week 24

    Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2017
  2. Study start2 Aug 2017
  3. Primary completion8 Aug 2022
  4. Study completion8 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
340 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03155347
Sponsor's protocol ID
YA29359
Status last verified
Nov 2023
First submitted
15 May 2017
Last updated
28 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40388166

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tocilizumab and MTX in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 20 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With an American College of Rheumatology (ACR) 20 (ACR20) Response at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03155347, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2023.

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