A Randomized, Double-Blind, Placebo-Controlled Clinical Study of the Efficacy and Safety of BCD-180 in Patients With Active Axial Spondyloarthritis
Overview
- Phase
- Phase 3
- Intervention
- anti-TRBV9 monoclonal antibody infusions
- Conditions
- Axial Spondyloarthritis
- Sponsor
- Biocad
- Enrollment
- 421
- Locations
- 32
- Primary Endpoint
- Proportion of subjects who achieved ASAS40 among bDMARDs and tsDMARD-naive subjects
- Status
- Active, Not Recruiting
- Last Updated
- last year
Overview
Brief Summary
The aim of the study is to evaluate the efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics of a fixed dose of study drug (BCD-180) in comparison with placebo in patients with active axial spondyloarthritis (axSpA). The study will include HLA-B27+ patients with radiographic (r-axSpA) and non-radiographic (nr-axSpA) who had no response to prior therapy with non-steroidal anti-rheumatic drugs (NSAIDs), have not received biologic disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and subjects with insufficient efficacy and/or loss of efficacy on bDMARDs and/or tsDMARDs.
Detailed Description
Subjects meeting the eligibility criteria will be randomized in 2 groups:bDMARDs and/or tsDMARD naive subjects and bDMARDs and/or tsDMARD experienced subjects will be randomized independently of each other. bDMARDs and tsDMARD-naive subjects (naïve) will be randomized into 3 groups: * BCD-180 (naïve); * Placebo (naïve); * Adalimumab. bDMARDs and/or tsDMARD experienced subjects (exp) will be randomized into 2 groups: * BCD-180 (exp); * Placebo (exp). After the primary endpoint assessment all subjects will be switched to BCD-180.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed Informed Consent Form for participation in the study.
- •Men and women aged \>18 years of age at the time of signing the Informed Consent Form for participation.
- •Positive test result for HLA-B
- •Presence of r-axSpA OR nr-axSpA according to the criteria provided below:
- •r-axSpA: axSpA diagnosis meets the ASAS 2009 criteria subject to the presence of radiographic signs of sacroiliitis according to the modified New York criteria (van der Linden et al. 1984) according to the central review. Subjects with an established diagnosis of ankylosing spondylitis according to the modified New York criteria may also be included in the study (van der Linden et al. 1984).
- •nr-axSpA: axSpA diagnosis meets ASAS 2009 criteria in the absence of radiographic signs of sacroiliitis according to the modified New York criteria (van der Linden et al. 1984) according to the central review.
- •Active disease at the screening and the randomization visit diagnosed based on both criteria:
- •ASDAS-CRP ≥2.1
- •assessment of the severity of back pain ≥4 on the NRS (BASDAI, question No. 2).
- •For subjects with nr-axSpA: presence of objective MRI signs of sacroiliitis (according to ASAS/OMERACT) as assessed by the central review AND/OR based on hsCRP level \>1.5 ULN at screening.
Exclusion Criteria
- •Refusal to take NSAIDs for the treatment of axSpA for any subjective reasons that do not have a clinical justification.
- •Use of the following medicines/procedures:
- •at any time before signing the ICF: total lymphoid irradiation;
- •at any time before signing the ICF: bone marrow transplantation, including stem and hematopoietic cell transplantation for any indications;
- •at any time before signing the ICF: splenectomy;
- •within 8 weeks before signing the ICF: treatment with immunoglobulins;
- •within 12 months before signing the ICF: use of immunosuppressants. Exception: glucocorticoids. A subject receiving glucocorticoids may be included in the study provided that the daily dose of glucocorticoids is ≤10 mg/day (calculated with reference to prednisolone) and was stable for at least 4 weeks prior to the Randomization Visit.
- •within 4 weeks before signing the ICF and during the screening period: use of synthetic DMARDs and thiopurines, including, but not limited to: 6-mercaptopurine, azathioprine, and others.
- •Exception: the medicinal products listed below if their dose was stable for 4 weeks before signing the ICF and during the screening period:
- •oral or parenteral methotrexate at a dose ≤25 mg/week, therapy shall be started at least 8 weeks before signing the ICF;
Arms & Interventions
bDMARDs and/or tsDMARD experienced subjects, BCD-180 group
Subjects in this arm will receive a fixed dose of BCD-180 infusions
Intervention: anti-TRBV9 monoclonal antibody infusions
bDMARDs and/or tsDMARD experienced subjects, Placebo group
Subjects in this arm will receive Placebo infusions till the assessment of the primary endpoint and then will be switched to BCD-180 infusions
Intervention: Placebo infusions
bDMARDs and tsDMARD-naive subjects, BCD-180 group
Subjects in this arm will receive a fixed dose of BCD-180 infusions and subcutaneous injections of placebo to maintain blindness of adalimumab therapy till the assessment of the primary endpoint, thereafter subjects will receive only BCD-180 infusions
Intervention: anti-TRBV9 monoclonal antibody infusions
bDMARDs and tsDMARD-naive subjects, BCD-180 group
Subjects in this arm will receive a fixed dose of BCD-180 infusions and subcutaneous injections of placebo to maintain blindness of adalimumab therapy till the assessment of the primary endpoint, thereafter subjects will receive only BCD-180 infusions
Intervention: Placebo subcutaneous injection
bDMARDs and tsDMARD-naive subjects, Placebo group
Subjects in this arm will receive Placebo infusions and subcutaneous injections of placebo to maintain blindness of adalimumab therapy till the assessment of the primary endpoint, thereafter subjects will be switched to BCD-180 infusions
Intervention: Placebo infusions
bDMARDs and tsDMARD-naive subjects, Placebo group
Subjects in this arm will receive Placebo infusions and subcutaneous injections of placebo to maintain blindness of adalimumab therapy till the assessment of the primary endpoint, thereafter subjects will be switched to BCD-180 infusions
Intervention: Placebo subcutaneous injection
bDMARDs and tsDMARD-naive subjects, Adalimumab group
Subjects in this arm will receive subcutaneous injections of adalimumab and infusions of placebo till the assessment of the primary endpoint, thereafter subjects will be switched to BCD-180 infusions
Intervention: Placebo infusions
bDMARDs and tsDMARD-naive subjects, Adalimumab group
Subjects in this arm will receive subcutaneous injections of adalimumab and infusions of placebo till the assessment of the primary endpoint, thereafter subjects will be switched to BCD-180 infusions
Intervention: Adalimumab subcutaneous injection
Outcomes
Primary Outcomes
Proportion of subjects who achieved ASAS40 among bDMARDs and tsDMARD-naive subjects
Time Frame: [Time Frame: week 24]
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more
Proportion of subjects who achieved ASAS40 among bDMARDs and/or tsDMARD-experienced subjects
Time Frame: [Time Frame: week 24]
Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more
Secondary Outcomes
- Proportion of subjects with the ASDAS-CRP <1.3([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of patients who achieved clinical response defined as an improvement of BASDAI by at least 50% compared to baseline([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in BASDAI([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASAS40 among subjects with nr-axSpA([Time Frame: week 24])
- Proportion of subjects with the ASDAS-CRP >3.5([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASAS40 among subjects with r-axSpA([Time Frame: week 24])
- Proportion of subjects with the ASDAS-CRP ≥1.3 - <2.1([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASDAS-MI (Major improvement)([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects with the ASDAS-CRP ≥2.1 - ≤3.5([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASDAS-CII (clinically important improvement)([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- ASDAS-CRP change from baseline([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASAS40([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in nocturnal back pain severity([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASAS20([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASAS5/6([Time Frame: weeks 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in BASMI([Time Frame: weeks 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in BASFI([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Proportion of subjects who achieved ASAS partial remission([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in the swollen joint count (44 joints)([Time Frame: weeks 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in MASES([Time Frame: weeks 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change from baseline in overall back pain severity (BASDAI No. 2)([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change in the patient global assessment of disease activity from baseline([Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156])
- Change in the quality of life score assessed with EQ-5D-3L questionnaire from baseline([Time Frame: weeks 12, 24, 48, 72, 84, 96, 108, 132, 156, 160])
- Change from baseline in SF-36 Physical Functioning compared to baseline([Time Frame: weeks 4, 8, 12, 16, 20, 24, 48, 72, 84, 96, 108, 120, 132, 144, 156, 160])
- Change in the concentration of hsCRP from baseline([Time Frame: weeks 4, 8, 12, 16, 20, 24, 48, 72, 84, 96, 108, 120, 132, 144, 156, 160])
- Proportion of subjects with adverse events([Time Frame: weeks 24, 160])
- Proportion of subjects with serious adverse events([Time Frame: weeks 24, 160])
- Change from baseline in SF-36 Mental Health compared to baseline([Time Frame: weeks 4, 8, 12, 16, 20, 24, 48, 72, 84, 96, 108, 120, 132, 144, 156, 160])
- Change in the WPAI score from baseline([Time Frame: weeks 12, 24, 48, 72, 84, 96, 120, 132, 144, 156, 160])
- Change in the ASAS HI score from baseline([Time Frame: weeks 12, 24, 48, 72, 84, 96, 120, 132, 144, 156, 160])
- Change in ESR from baseline([Time Frame: weeks 4, 8, 12, 16, 20, 24, 48, 72, 84, 96, 108, 120, 132, 144, 156, 160])
- Changes in the SPARCC score (spine, SIJ) from baseline([Time Frame: weeks 24, 48, 108, 144, 156])
- Changes in mSASSS scores from baseline([Time Frame: weeks 48, 108, 144,156])
- Proportion of subjects prematurely withdrawn from the study due to adverse events([Time Frame: weeks 24, 160])
- Proportion of subjects with grade 3 or higher adverse events according to CTCAE 5.0([Time Frame: weeks 24, 160])