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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03155347
• Other study ID #: YA29359
• Status: Completed
• Phase: Phase 3
• Start date: August 2, 2017
• Est. completion date: August 8, 2022

Study information

• Verified date: November 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 340
• Est. completion date: August 8, 2022
• Est. primary completion date: August 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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• All treatment with non-biological DMARDs except MTX should be withdrawn at least 2 weeks prior to baseline (leflunomide for 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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• 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.
• MTX
Participants will receive MTX stable doses at 10 to 25 mg orally.
• Placebo Matched to MTX
Placebo matched to MTX.
• Placebo Matched to Tocilizumab
Placebo matched to tocilizumab.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Baotou Medical College	Baotou
China	Beijing Union Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	China-Japan Friendship Hospital	Beijing City
China	Peking University First Hospital	Beijing City
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	The First Affiliated Hospital of Anhui Medical University	Hefei
China	Affiliated Hospital of Inner Mongolia Medical College	Hohhot
China	The First Hospital of Jiaxing	Jiaxing
China	Qilu Hospital of Shandong University	Jinan
China	The First Affilliated Hospital of Kunming Medical College	Kunming
China	Jiangsu Province Hospital	Nanjing
China	Pingxiang People Hospital	Pingxiang City
China	Shengjing Hospital of China Medical University	ShenYang
China	The Second Hospital of Shanxi Medical University	Taiyuan
China	Tianjin Medical University General Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology (ACR) 20 (ACR20) Response at Week 24		Week 24
Secondary	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		Week 24
Secondary	Percentage of Participants With Remission at Week 24, Defined as DAS28-ESR Score of Less Than (<) 2.6		Week 24
Secondary	Change From Baseline in Tender Joint Count (TJC) at Week 24		Baseline, Week 24
Secondary	Change From Baseline in Swollen Joint Count (SJC) at Week 24		Baseline, Week 24
Secondary	Change From Baseline in C-reactive Protein (CRP) Levels at Week 24		Baseline, Week 24
Secondary	Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24		Baseline, Week 24
Secondary	Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score at Week 24		Baseline, Week 24
Secondary	Change From Baseline in the Physician's Global Assessment of Disease Activity VAS Score at Week 24		Baseline, Week 24
Secondary	Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24		Baseline, Week 24
Secondary	Change From Baseline in the Patient's Pain VAS at Week 24		Baseline, Week 24
Secondary	Change From Baseline in DAS28-ESR at Week 24		Baseline, Week 24
Secondary	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		56 weeks
Secondary	Percentage of Participants With anti-Tocilizumab Antibody		Baseline, Week 12, Week 24, Week 48, at the time of withdrawal up to approximately 48 weeks
Secondary	Serum Interleukin-6 (IL-6) Levels		Baseline, predose (Hour 0) on Weeks 2, 4, 8, 12, 16, 24, 48
Secondary	Serum Soluble Interleukin-6 Receptor (sIL-6R) Levels		Baseline, predose (Hour 0) on Weeks 2, 4, 8, 12, 16, 24, 48
Secondary	Maximum Observed Plasma Concentration (Cmax) of Tocilizumab		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
Secondary	Minimum Observed Plasma Concentration (Cmin) of Tocilizumab		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
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tocilizumab		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
Secondary	Plasma Decay Half-Life (t1/2) of Tocilizumab		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
Secondary	Area Under the Curve from Time Zero to end of dosing interval (AUCtau) of Tocilizumab		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
Secondary	Accumulation Ratio for Area Under the Concentration Time Curve (Rac, AUC) of Tocilizumab		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
Secondary	Accumulation Ratio for Maximum Observed Plasma Concentration (Rac, Cmax) of Tocilizumab		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
Secondary	Accumulation Ratio for Minimum Observed Plasma Trough Concentration (Rac, Cmin) of Tocilizumab		predose (Hour 0) on Day 14, 84
Secondary	Plasma Trough Concentration (Ctrough) of Tocilizumab		predose (Hour 0) on Day 0, 14, 28, 56, 84, 98, 112, 140, 168, and 336
Secondary	Percentage of Participants With ACR50 Responses at Week 24		Week 24
Secondary	Percentage of Participants With ACR70 Responses at Week 24		Week 24