International Multicenter Comparative Randomized Double-blind Placebo-controlled Clinical Study of Efficacy and Safety of BCD-089 in Different Dosing Regimens in Patients With Active Rheumatoid Arthritis
Overview
- Phase
- Phase 2
- Intervention
- BCD-089, 162 mg, s/c, qw
- Conditions
- Seropositive RA
- Sponsor
- Biocad
- Enrollment
- 105
- Locations
- 4
- Primary Endpoint
- ACR20
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The study is Phase II randomized, double-blind, placebo-controlled clinical trial to evaluate efficacy and safety, pharmacokinetics and pharmacodynamics of 2 dosing regimens (qw and q2w, s/c) of monoclonal antibody to IL6R (BCD-089) in patients with active rheumatoid arthritis and inadequate response to methotrexate.
Detailed Description
IL-6 is a new potential therapeutic target which plays important role in pathogenesis of several autoimmune disorders including rheumatoid arthritis. BCD-089 is a novel fully human monoclonal antibody against the interleukin-6 receptor developed by JCS BIOCAD (Russia) which is successfully passed phase I clinical study. Fixed dose of 162 mg was chosen for evaluation in phase II clinical trial. Comparisons in terms of efficacy, safety, PK/PD will be made for every week and every other week dosing for 54 weeks. W0-W12, planed as blinded, "main" period of the study, consists of three arms (n=35, each) - 2 study arms and placebo arm and served to test the hypothesis of superiority of BCD-089 to placebo. W12-W54, planned as "open" period of the study and served to evaluate long-therm safety and efficacy of BCD-089 in patients with active rheumatoid arthritis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent
- •Males and females aged 18 - 80 years, at IC signing date.
- •Diagnosis of rheumatoid arthritis, according to ACR 2010 criteria, at least for 6 month prior to IC signing date.
- •Active rheumatoid arthritis at IC signing date.
- •Therapy with methotrexate for at least 3 month prior to IC signing date.
- •Stable dose of methotrexate (10-25 mg/week) for 4 weeks prior to IC signing date.
- •Persistent activity of RA despite methotrexate (provided by Sponsor) therapy within screening period (4-6weeks).
- •Patients, with following parameters of laboratory investigations:
- •Hemoglobin ≥ 80 g/l;
- •White blood cells ≥ 3,0×109/l;
Exclusion Criteria
- •History of therapy with tocilizumab or other monoclonal antibodies to IL6R / IL
- •History of therapy with rituximab or other B-cell depleting medicines.
- •Felty's syndrome (any form).
- •ACR1991 functional status IV.
- •Low disease activity of rheumatoid arthritis (DAS28-CRP(4) \< 3,2).
- •Known allergy or intolerance of any investigational drug/placebo ingredients.
- •Concomitant medication including any of the following:
- •Requirement \> 10 mg / day of oral prednisolone (or equivalent);
- •Requirement \< 10 mg / day of oral prednisolone (or equivalent), if the dose was not stable for 4 weeks prior the date of informed consent sign (it is allowed to include patients on topical steroids);
- •Requirement of NSAID, if dose was not stable for 4 weeks prior the date of informed consent sign (it is allowed to include patients received NSAID occasionally to treat intercurrent fever or allergy).
Arms & Interventions
BCD-089 weekly
Intervention: BCD-089, 162 mg, s/c, qw
BCD-089 biweekly
Intervention: BCD-089, 162 mg, s/c, q2w
Placebo
Intervention: placebo
Outcomes
Primary Outcomes
ACR20
Time Frame: week 12
Secondary Outcomes
- ACR50(week 4, week 8, week 16, week 24, week 36, week 48, week 52)
- Low RA activity(week 4, week 8, week 12, week 16, week 24, week 36, week 48, week 52)
- Pharmacodynamics of BCD-089(week 0 - week 12)
- ACR70(week 4, week 8, week 16, week 24, week 36, week 48, week 52)
- Pharmacokinetics of BCD-089(week 0 - week 12)
- RA remission(week 24, week 36, week 48, week 52)
- X-ray signs of RA(week52)