Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of Various Doses of BCD-085 in Patients With Active Ankylosing Spondylitis
- Registration Number
- NCT02763111
- Lead Sponsor
- Biocad
- Brief Summary
BCD-085-3 is a next step in clinical investigation of BCD-085. BCD-085 is a monoclonal antibody to interleukin 17. During the trial patients with active ankylosing spondylitis will receive 40, 80 or 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. Efficacy and safety parameters will be evaluated.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 88
- Written informed consent
- Age between 18 and 65 years
- Active ankylosing spondylitis according to modified criteria of New York classification (1984), that was diagnosed at least 3 months prior to screening.
- Active disease according to BASDAI (score 4 or more) if nonsteroidal antiinflammatory drugs were used in the last 3 month prior to screening.
- Mean backache intensity equals 4 points or more.
- If patient have had biologic therapy to treat ankylosing spondylitis for at least 3 months, there was no positive results of such treatment or patient revealed intolerance to the drug. This therapy must be discontinued at least 12 weeks before enrollment in the study.
- Female patients have negative urine pregnancy test.
- Patient has no history of tuberculosis.
- Patients have negative results of Diaskintest.
- Patient has no history of alcohol or drug abuse.
- Total spinal ankylosis.
- Allergy or intolerance of monoclonal antibodies or any excipients of study drugs.
- Previous receipt of anti-interleukin 17 drugs or anti-interleukin 17 receptor drugs.
- Prior use of two or more biologics to tumor necrosis factor alfa.
- Prior use of two or more biologics to other targets. Previous receipt of monoclonal antibodies if they were cancelled less that in 12 weeks before signing informed consent.
- Patient is taking corticosteroids for up to 4 weeks in a dose more than 10 mg (recalculated to prednisolone) before signing informed consent and during screening, or in a dose less than 10 mg (recalculated to prednisolone) if it was not stable.
- Prior use of disease-modifying antirheumatic drugs including methotrexate, sulfasalazin, chloroquine or hydroxychloroquine for up to 4 weeks before randomization, if their dose was not stable for up to 4 weeks before signing informed consent and during screening.
- Prior use of live or attenuated vaccines for up to 8 weeks before signing informed consent.
- Prior use of alkylating agents for up to 12 months prior to signing informed consent.
- Intraarticular use of corticosteroids for up to 4 weeks before randomization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BCD-085, 120 mg BCD-085 Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. BCD-085, 40 mg BCD-085 Patient will receive 40 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. Placebo Placebo Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. BCD-085, 80 mg BCD-085 Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12.
- Primary Outcome Measures
Name Time Method Ratio of patients with ASAS20 response after 16 weeks of therapy Week 16 Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 20% or more after 16 weeks of therapy with BCD-085.
- Secondary Outcome Measures
Name Time Method Frequency of local reactions 16 weeks Frequency of AE/SAE 3-4 grade CTCAE 4.03 16 weeks Proportion of patients with deterioration of roentgenologic signs of sacroileitis after 16 weeks of treatment Week 16 Mean C-reactive protein concentration at screening and after 4, 8, 12 and 16 weeks of treatment. Screening, Week 4, Week 8, Week 12, Week 16 Ratio of patients with ASAS40 response after 4, 8, 12, 16 weeks of therapy Week 4, Week 8, Week 12, Week 16 Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 40% or more after 4, 8, 12, 16 weeks of therapy with BCD-085.
Mean BASDAI score at screening and after 4, 8, 12, 16 weeks of therapy Screening, Week 4, Week 8, Week 12, Week 16 Mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy Screening, Week 4, Week 8, Week 12, Week 16 Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy measured by Cloth Tape Measure Technique
Frequency of AE/SAE 16 weeks Ratio of patients with ASAS5/6 response after 4, 8, 12, 16 weeks of therapy Week 4, Week 8, Week 12, Week 16 Ratio of patients who developed a response in at least 5 of 6 criteria of ankylosing spondylitis assessment score (ASAS) after 4, 8, 12, 16 weeks of therapy with BCD-085.
Mean MASES score at screening and after 4, 8, 12, 16 weeks of therapy Screening, Week 4, Week 8, Week 12, Week 16 Mean Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at screening and after 4, 8, 12, 16 weeks of therapy
Mean SF-36 score at screening and after 8 and 16 weeks of therapy Screening, Week 8, Week 16 Mean Short Form-36 (SF36) score at screening and after 8, 16 weeks of therapy
Т½ 0 to 168 hours post-dose Half-life of BCD-085 in blood after drug injection
Ratio of patients with ASAS20 response after 4, 8, 12 weeks of therapy Week 4, Week 8, Week 12 Ratio of patients who developed a decrease in ankylosing spondylitis assessment score (ASAS) by 20% or more after 4, 8, 12 weeks of therapy with BCD-085.
Cmin 0 to 168 hours post-dose Minimal concentration of BCD-085 in blood after drug injection
Cmax 0 to 168 hours post-dose Maximal concentration of BCD-085 in blood after drug injection
Proportion of patients who developed binding and neutralizing antibodies to BCD-085 16 weeks Mean BASMI score at screening and after 4, 8, 12, 16 weeks of therapy Screening, Week 4, Week 8, Week 12, Week 16 Mean Bath Ankylosing Spondylitis Metrology Index (BASMI) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean BASFI score at screening and after 4, 8, 12, 16 weeks of therapy Screening, Week 4, Week 8, Week 12, Week 16 Mean Bath Ankylosing Spondylitis Functional Index (BASFI) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean ASDAS-CRP score at screening and after 4, 8, 12, 16 weeks of therapy Screening, Week 4, Week 8, Week 12, Week 16 Mean Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) score at screening and after 4, 8, 12, 16 weeks of therapy
Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy Screening, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16 Mean pain score during a day at screening and after 1, 2, 4, 8, 12, 16 weeks of therapy measured by Visual Analog Scale for Pain
Frequency of withdrawals due to AE/SAE 16 weeks AUC (0-168h) 0 to 168 hours post-dose Area under curve from 0 to 168 hours of BCD-085 in blood after drug injection
AUC0-∞ 0 to 168 hours post-dose Area under curve from 0 to infinity of BCD-085 in blood after drug injection
Тmax 0 to 168 hours post-dose Time before Cmax of BCD-085 is reached in blood after drug injection
Кel 0 to 168 hours post-dose Elimination rate constant of BCD-085 in blood after drug injection
Cl 0 to 168 hours post-dose Clearance of BCD-085 in blood after drug injection