Ankylosing Spondylitis
Conditions
Keywords
ankylosing spondylitis, interleukin 17, monoclonal antibody
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.
Interventions
DRUGBCD-085
OTHERPlacebo
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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 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 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 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 |
| 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 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 | — |
| Frequency of AE/SAE | 16 weeks | — |
| 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 |
| 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 |
| 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. |
| Frequency of local reactions | 16 weeks | — |
| Frequency of AE/SAE 3-4 grade CTCAE 4.03 | 16 weeks | — |
| Frequency of withdrawals due to AE/SAE | 16 weeks | — |
| Cmin | 0 to 168 hours post-dose | Minimal concentration of BCD-085 in blood after drug injection |
| 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 |
| Cmax | 0 to 168 hours post-dose | Maximal concentration 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 |
| Т½ | 0 to 168 hours post-dose | Half-life of BCD-085 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 |
| Proportion of patients who developed binding and neutralizing antibodies to BCD-085 | 16 weeks | — |
| Proportion of patients with deterioration of roentgenologic signs of sacroileitis after 16 weeks of treatment | Week 16 | — |
Outcome results
None listed