Overview

This trial has been completed.

Condition rheumatoid arthritis
Treatments azathioprine, chloroquine, hydroxychloroquine, leflunomide, methotrexate, sulfasalazine, tocilizumab
Phase phase 3
Sponsor Hoffmann-La Roche
Start date November 2013
End date July 2016
Trial size 100 participants
Trial identifier NCT01941095, 2013-000359-42, ML28695

Summary

This multicenter, open-label, single arm study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab as monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active rheumatoid arthritis who are either naïve to or have an inadequate response to prior non-biologic or/and biologic DMARDs. The anticipated time on study treatment is 52 weeks. Those participants who will complete the 60-week study period and have achieved Disease Activity Score (DAS) 28 remission or a good European League Against Rheumatism (EULAR) response at 52 weeks will be eligible to enter the extension phase until tocilizumab is commercially available and reimbursed in Greece.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
Arm
(Experimental)
Participants will receive tocilizumab 162 milligrams (mg) SC injection once a week (QW) either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment is according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen, they may either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52. Participants who will complete the treatment phase before tocilizumab is commercially available will enter an extension phase until tocilizumab is commercially available in Greece. Permitted DMARDs include methotrexate, azathioprine, chloroquine, hydroxychloroquine, leflunomide, and sulfasalazine.
azathioprine
Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to Baseline.
chloroquine
Participants may receive chloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to Baseline.
hydroxychloroquine
Participants may receive hydroxychloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to Baseline.
leflunomide
Participants may receive leflunomide as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to Baseline.
methotrexate
Participants may receive methotrexate as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to Baseline.
sulfasalazine
Participants may receive sulfasalazine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to Baseline.
tocilizumab RoActemra, Actemra
Participants will receive tocilizumab at a fixed dose of 162 mg SC QW either as monotherapy or in combination with non-biologic DMARDs.

Primary Outcomes

Measure
Percentage of Participants Who Achieve DAS28 Remission (DAS28 Score Less Than [<] 2.6) at Week 24
time frame: Week 24

Secondary Outcomes

Measure
Percentage of Participants Who Maintain DAS28 Remission or Low Disease Activity (LDA) from Week 24 to Week 52 Among Participants on Tocilizumab Monotherapy from Week 24
time frame: From Week 24 to Week 52
Percentage of Participants Who Achieve DAS28 Remission or LDA from Week 24 to Week 52 Among Participants with Intensification of Methotrexate/Other Non-biologic DMARDs in Combination with Tocilizumab Since Week 24
time frame: From Week 24 to Week 52
Change From Baseline in DAS28 Scores Based on Erythrocyte Sedimentation Rate (ESR)
time frame: Baseline to Week 52
Change from Baseline in American College of Rheumatology (ACR) Scores
time frame: Baseline to Week 52
Percentage of Participants With Good, Moderate, or No Response According to EULAR Response Criteria
time frame: Baseline, Week 52
Change from Baseline in Simplified Disease Activity Index (SDAI) Scores
time frame: Baseline to Week 52
Change from Baseline in Clinical Disease Activity Index (CDAI) Scores
time frame: Baseline to Week 52
Change from Baseline in Tender Joint Count (TJC)
time frame: Baseline to Week 52
Change from Baseline in Swollen Joint Count (SJC)
time frame: Baseline to Week 52
Percentage of Participants with Corticosteroid Dose Reduction or Discontinuation
time frame: Baseline up to Week 52
Percentage of Participants by Reason (Categories) for Corticosteroid Dose Reduction or Discontinuation
time frame: Baseline up to Week 52
Percentage of Participants with Adverse Events
time frame: Baseline up to Week 52
Percentage of Participants with Anti-Tocilizumab Antibodies
time frame: Baseline, Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
Soluble Interleukin-6 Receptor (sIL-6R) Levels
time frame: Baseline, Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
Tocilizumab Serum Levels
time frame: Pre-dose (Hour 0) on Days 1, 84, 168, 252, and 364
Patient Global Assessment of Disease Activity (PGA), Using Visual Analogue Scale Score (VAS)
time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Patient Assessment of Pain, Using VAS Score
time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Health Assessment Questionnaire - Disease Index (HAQ-DI) Score
time frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Percentage of Participants Who Receive All Planned Study Medication (Compliance)
time frame: Baseline up to Week 52
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Score
time frame: Baseline, Week 2, 4, 8, 12, 16, 20, 24

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria - Oral corticosteroids (less than or equal to [/=] 4 weeks prior to baseline - Permitted non biologic DMARDs are allowed if a stable dose for at least 4 weeks prior to baseline - Receiving treatment on an outpatient basis, not including tocilizumab - Females of childbearing potential and males with female partners of childbearing potential must agree to use a reliable means of contraception during the study; females of childbearing potential must use a reliable means of contraception for at least 3 month following the last dose of tocilizumab Exclusion Criteria: - Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline - Rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjögren's syndrome with rheumatoid arthritis is permitted - Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis - Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16 - Prior history of or current inflammatory joint disease other than rheumatoid arthritis - Participants with lack of peripheral venous access - Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline - Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of screening - Previous treatment with any cell-depending therapies - Treatment with IV gamma globulin, plasmapheresis within 6 months of baseline - Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline - Immunization with a live/attenuated vaccine within 4 weeks prior to baseline - Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation - History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies - Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease - Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections - Any major episode of infection requiring hospitalization of treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening - Active Tuberculosis (TB) requiring treatment within the previous 3 years - Positive for hepatitis B surface antigen or hepatitis C antibody - Primary or secondary immunodeficiency (history of or currently active) - Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured) , or breast cancer diagnosed within the previous 20 years - Pregnancy or breast feeding women - History of alcohol, drug or chemical abuse within 1 year prior to screening - Neuropathies or other conditions that interfere with pain evaluation

Additional Information

Official title Multicenter, Open-label, Phase IIIb Study to Evaluate the Safety and Tolerability of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Methotrexate or Other Non-biologic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis
Trial information was received from ClinicalTrials.gov and was last updated in January 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.