Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of Various Doses of BCD-085 in Patients With Active Ankylosing Spondylitis

Study Overview
=================
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.

Official Title
-----------------
International Multi-center Comparative Randomized Double-blind Placebo-controlled Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of BCD-085 in Various Doses in Patients With Active Ankylosing Spondylitis

Conditions
-----------------
Ankylosing Spondylitis

Intervention / Treatment
-----------------
* Drug: BCD-085
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-085, 40 mg<br>Patient will receive 40 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. | Drug: BCD-085<br> <br> |
| Experimental: BCD-085, 80 mg<br>Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. | Drug: BCD-085<br> <br> |
| Experimental: BCD-085, 120 mg<br>Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. | Drug: BCD-085<br> <br> |
| Placebo Comparator: Placebo<br>Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10, 12. | Other: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of patients with ASAS20 response after 16 weeks of therapy | 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. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of patients with ASAS20 response after 4, 8, 12 weeks of therapy | 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. | Week 4, Week 8, Week 12 | 
| Ratio of patients with ASAS40 response after 4, 8, 12, 16 weeks of therapy | 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. | Week 4, Week 8, Week 12, Week 16 | 
| Ratio of patients with ASAS5/6 response after 4, 8, 12, 16 weeks of therapy | 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. | Week 4, Week 8, Week 12, Week 16 | 
| Mean BASDAI score at screening and after 4, 8, 12, 16 weeks of therapy | Mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score at screening and after 4, 8, 12, 16 weeks of therapy | Screening, Week 4, Week 8, Week 12, Week 16 | 
| Mean BASMI score at screening and after 4, 8, 12, 16 weeks of therapy | Mean Bath Ankylosing Spondylitis Metrology Index (BASMI) score at screening and after 4, 8, 12, 16 weeks of therapy | Screening, Week 4, Week 8, Week 12, Week 16 | 
| Mean MASES score at screening and after 4, 8, 12, 16 weeks of therapy | Mean Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 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 | Mean chest excursion at screening and after 4, 8, 12, 16 weeks of therapy measured by Cloth Tape Measure Technique | Screening, Week 4, Week 8, Week 12, Week 16 | 
| Mean BASFI score at screening and after 4, 8, 12, 16 weeks of therapy | Mean Bath Ankylosing Spondylitis Functional Index (BASFI) score at screening and after 4, 8, 12, 16 weeks of therapy | Screening, Week 4, Week 8, Week 12, Week 16 | 
| Mean ASDAS-CRP score at screening and after 4, 8, 12, 16 weeks of therapy | Mean Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) score at screening and after 4, 8, 12, 16 weeks of therapy | Screening, Week 4, Week 8, Week 12, Week 16 | 
| Mean SF-36 score at screening and after 8 and 16 weeks of therapy | Mean Short Form-36 (SF36) score at screening and after 8, 16 weeks of therapy | Screening, Week 8, Week 16 | 
| Mean pain score during a day at screening and after 1, 2, 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 measured by Visual Analog Scale for Pain | Screening, Week 1, Week 2, Week 4, Week 8, Week 12, Week 16 | 
| 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 | 
| Frequency of AE/SAE |  | 16 weeks | 
| 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 | Minimal concentration of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| AUC (0-168h) | Area under curve from 0 to 168 hours of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| AUC0-∞ | Area under curve from 0 to infinity of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| Cmax | Maximal concentration of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| Тmax | Time before Cmax of BCD-085 is reached in blood after drug injection | 0 to 168 hours post-dose | 
| Т½ | Half-life of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| Кel | Elimination rate constant of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| Cl | Clearance of BCD-085 in blood after drug injection | 0 to 168 hours post-dose | 
| Proportion of patients who developed binding and neutralizing antibodies to BCD-085 |  | 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
interleukin 17, ankylosing spondylitis, monoclonal antibody