Clinical trial 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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* All treatment with non-biological DMARDs except MTX should be withdrawn at least 2 weeks prior to baseline (leflunomide for \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

Primary outcomes:
measure: Percentage of Participants With an American College of Rheumatology (ACR) 20 (ACR20) Response at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: 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
timeFrame: Week 24
measure: Percentage of Participants With Remission at Week 24, Defined as DAS28-ESR Score of Less Than (<) 2.6
timeFrame: Week 24
measure: Change From Baseline in Tender Joint Count (TJC) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Swollen Joint Count (SJC) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in C-reactive Protein (CRP) Levels at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in the Patient's Pain VAS at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in DAS28-ESR at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 56 weeks
measure: Percentage of Participants With anti-Tocilizumab Antibody
timeFrame: Baseline, Week 12, Week 24, Week 48, at the time of withdrawal up to approximately 48 weeks
measure: Serum Interleukin-6 (IL-6) Levels
timeFrame: Baseline, predose (Hour 0) on Weeks 2, 4, 8, 12, 16, 24, 48
measure: Serum Soluble Interleukin-6 Receptor (sIL-6R) Levels
timeFrame: Baseline, predose (Hour 0) on Weeks 2, 4, 8, 12, 16, 24, 48
measure: Maximum Observed Plasma Concentration (Cmax) of Tocilizumab
timeFrame: 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
measure: Minimum Observed Plasma Concentration (Cmin) of Tocilizumab
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tocilizumab
timeFrame: 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
measure: Plasma Decay Half-Life (t1/2) of Tocilizumab
timeFrame: 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
measure: Area Under the Curve from Time Zero to end of dosing interval (AUCtau) of Tocilizumab
timeFrame: 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
measure: Accumulation Ratio for Area Under the Concentration Time Curve (Rac, AUC) of Tocilizumab
timeFrame: 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
measure: Accumulation Ratio for Maximum Observed Plasma Concentration (Rac, Cmax) of Tocilizumab
timeFrame: 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
measure: Accumulation Ratio for Minimum Observed Plasma Trough Concentration (Rac, Cmin) of Tocilizumab
timeFrame: predose (Hour 0) on Day 14, 84
measure: Plasma Trough Concentration (Ctrough) of Tocilizumab
timeFrame: predose (Hour 0) on Day 0, 14, 28, 56, 84, 98, 112, 140, 168, and 336
measure: Percentage of Participants With ACR50 Responses at Week 24
timeFrame: Week 24
measure: Percentage of Participants With ACR70 Responses at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
city: Beijing City
country: China
facility: China-Japan Friendship Hospital
city: Beijing City
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Beijing Union Hospital
city: Bengbu
country: China
facility: Affiliated Hospital of Bengbu Medical College
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Harbin
country: China
facility: The 1st Affiliated Hospital of Harbin Medical University
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical College
city: Jiaxing
country: China
facility: The First Hospital of Jiaxing
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Kunming
country: China
facility: The First Affilliated Hospital of Kunming Medical College
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Pingxiang City
country: China
facility: Pingxiang People Hospital
city: ShenYang
country: China
facility: Shengjing Hospital of China Medical University
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
Study officials:
References: