Overview

This trial is active, not recruiting.

Condition rheumatoid arthritis
Treatments dmard, methotrexate, tocilizumab [roactemra/actemra]
Phase phase 3
Sponsor Hoffmann-La Roche
Start date September 2013
End date June 2015
Trial size 401 participants
Trial identifier NCT01995201, 2013-002429-52, ML28709

Summary

This multicenter, open-label study will evaluate the efficacy and safety of subcutaneously administered RoActemra/Actemra (tocilizumab) as monotherapy or in combination with methotrexate or other non-biologic DMARDs in patients with active rheumatoid arthritis and an inadequate response to non-biologic DMARDs or to one anti-TNF. In Phase 1, all patients will receive RoActemra/Actemra 162 mg subcutaneously (sc) weekly for Weeks 1 to 24, with or without methotrexate or other non-biologic DMARDs. For Part 2, patients who achieve sustained clinical DAS28-ESR remission at Weeks 20 and 24 will be randomized to receive RoActemra/Actemra 162 mg sc either weekly or every 2 weeks for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs. Patients who do not achieve sustained clinical remission but achieve low disease activity (DAS-ESR

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
dmard
non-biological disease-modifying antirheumatic drugs at stable dose
methotrexate
stable dose
tocilizumab [roactemra/actemra]
162 mg subcutaneously (SC) qw, Weeks 1-24
(Experimental)
dmard
non-biological disease-modifying antirheumatic drugs at stable dose
methotrexate
stable dose
tocilizumab [roactemra/actemra]
162 mg SC qw or q2w, Weeks 24-48
(Experimental)
dmard
non-biological disease-modifying antirheumatic drugs at stable dose
methotrexate
stable dose
tocilizumab [roactemra/actemra]
162 mg SC qw, Weeks 24-48

Primary Outcomes

Measure
Proportion of patients achieving sustained clinical remission (DAS-ESR <2.6) at Weeks 20 and 24
time frame: 24 weeks

Secondary Outcomes

Measure
Mean change in DAS28-ESR (Arm A)
time frame: from baseline to Week 48
Proportion of patients remaining in clinical remission (Arm A)
time frame: Week 48
Rates of flare (defined as change in DAS28-ESR >1.2) (Arm A)
time frame: 48 weeks
American College of Rheumatology (ACR) response scores
time frame: 48 weeks
Response according to European League Against Rheumatism (EULAR) response scores
time frame: 48 weeks
Change in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)
time frame: from baseline to Week 48
Change in total/swollen joint counts (TJC/SJC)
time frame: from baseline to Week 48
Proportion of patients who achieve DAS28-ESR remission (DAS28-ESR <2.6)
time frame: Week 48
Proportion of patients who achieve CDAI/SDAI) remission (CDAI <2.8/SDAI <3.3)
time frame: Week 48
Proportion of patients who achieve low disease activity based on DAS28-ESR criteria (DAS28-ESR </=3.2)
time frame: Week 48
Proportion of patients who achieve low disease activity based on CDAI/SDAI scores (CDAI <10/SDAI <11)
time frame: Week 48
Safety: Incidence of adverse events
time frame: 56 weeks
Immunogenicity: Incidence of anti-tocilizumab antibodies
time frame: 56 weeks
Patient reported outcomes: Health assessment questionnaires/VAS scales
time frame: 48 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients, >/= 18 years of age - Active rheumatoid arthritis (DAS28-ESR > 3.2), according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria of > 6 months duration - Patients with intolerance or inadequate response to methotrexate or other non-biologic DMRADs or inadequate response to a first ant-TNF agent - Oral corticosteroids (/= 4 weeks prior to baseline - Permitted non-biologic DMRAD is allowed if at stable dose for at least 4 weeks prior to baseline - Females of childbearing potential and males with female partners of childbearing potential must be using a reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of RoActemra/Actemra - Patients with intolerance or inadequate response to methotrexate or other non-biologic DMARDs or inadequate response to first anti-TNF agent 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 RA or significant systemic involvement secondary to RA; secondary Sjögren's syndrome with RA is permitted - Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis - Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16 - Prior history of current inflammatory joint disease other than RA - Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline - Treatment with any investigational agent with four weeks (or five-half lives of the investigational drug, whichever is longer) of screening - Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline - Previous treatment with Abatacept - History of severe allergic of anaphylactic reactions to human, humanized, or murine monoclonal antibodies - Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disease - History of diverticulitis, diverticulitis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation - Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections or nail beds) - Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening - Active TB requiring treatment within the previous 3 years - Positive hepatitis B or hepatitis C - Primary or secondary immunodeficiency (history of or currently active) - Evidence of active malignant disease, malignancies diagnosed with the previous 10 years (including hematological malignancies and solid tumors, except basal of squamous cell carcinoma of the skin diagnosed within the previous 20 years - Pregnant and lactating women - History of alcohol, drug, or chemical abuse within 1 year prior to screening - Neuropathies or other conditions that might interfere with pain evaluation - Inadequate hematological, real of liver function

Additional Information

Official title A Phase IIIb Study to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous (SC) Tocilizumab (TCZ) Given as Monotherapy or in Combination With Methotrexate (MTX) or Other Non Biologics DMARDs in Subjects With Rheumatoid Arthritis
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.