International Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of BCD-085 in Various Doses in Patients With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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BCD-085-2 is a next step in clinical investigation of BCD-085. BCD-085 is a monoclonal antibody to interleukin 17. During BCD-085-2 trial patients with moderate to severe plaque psoriasis, in whom poor response to previous treatment including UV-therapy and biologic drugs was registered, will receive 40, 80 or 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. Efficacy and safety parameters will be evaluated.

Official Title
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International Multi-center Comparative Randomized Clinical Trial to Evaluate Efficacy and Safety of Multiple Subcutaneous Injections of BCD-085 in Various Doses in Patients With Moderate to Severe Plaque Psoriasis

Conditions
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Psoriasis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age between 18 and 65 years Diagnosis of plaque psoriasis with stable course of the disease during last 6 months prior to enrollment in the study. Patient have had at least 1 course of phototherapy or systemic therapy of psoriasis or are candidates for such treatment. BSA affected by psoriasis ≥ 10%, PASI score ≥ 12, sPGA score ≥ 3. If patient have had biologic therapy 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. Patients are able to perform all procedures planed by protocol. Patients are ready for contraception with reliable methods starting 2 weeks before entering the study, and up to 4 weeks after the last dose of study drug. Exclusion Criteria: Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions at the time of the screening visit (e.g., eczema) that would interfere with evaluations of the effect of investigational product on psoriasis. 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 drugs including methotrexate, sulfasalazin and cyclosporin for up to 4 weeks before signing informed consent, 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 phototherapy including selective phototherapy and photochemotherapy for up to 4 weeks before signing informed consent.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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. | Drug: BCD-085<br> <br> * Other names: monoclonal antibody to interleukin 17;|
| Experimental: BCD-085, 80 mg<br>Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. | Drug: BCD-085<br> <br> * Other names: monoclonal antibody to interleukin 17;|
| Experimental: BCD-085, 120 mg<br>Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. | Drug: BCD-085<br> <br> * Other names: monoclonal antibody to interleukin 17;|
| Placebo Comparator: Placebo<br>Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With PASI 75 Response After 12 Weeks of Therapy | The PASI allows evaluating the extent and severity of skin symptoms of psoriasis. Body is divided into 4 areas for scoring (head, arms, trunk, legs); each area is scored by itself and scores are combined for final PASI: 0 (no disease) to 72 (maximal disease). The proportion of patients with PASI 75 was defined as patients achieving 75% or more improvement at Week 12 of therapy with BCD-085 from baseline. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With PASI75 Response After 4 and 8 Weeks of Therapy | The PASI allows evaluating the extent and severity of skin symptoms of psoriasis. Body is divided into 4 areas for scoring (head, arms, trunk, legs); each area is scored by itself and scores are combined for final PASI: 0 (no disease) to 72 (maximal disease). The proportion of patients with PASI 75 was defined as patients achieving 75% or more improvement from baseline. | Week 4, Week 8 | 
| Number of Patients With PASI50 and PASI90 Response After 4, 8 and 12 Weeks of Therapy | The PASI allows evaluating the extent and severity of skin symptoms of psoriasis. Body is divided into 4 areas for scoring (head, arms, trunk, legs); each area is scored by itself and scores are combined for final PASI: 0 (no disease) to 72 (maximal disease). The proportion of patients with PASI 50 and PASI 90 was defined as patients achieving 50% or more and 90% or more improvement from baseline, respectively. | Week 4, Week 8, Week 12 | 
| Relative Change in PASI Score After 4, 8 and 12 Weeks of Therapy With BCD-085 | The PASI allows evaluating the extent and severity of skin symptoms of psoriasis. Body is divided into 4 areas for scoring (head, arms, trunk, legs); each area is scored by itself and scores are combined for final PASI: 0 (no disease) to 72 (maximal disease). Relative (percentage) change in PASI score from baseline (screening) is calculated as 100 x (baseline value - time point t value) / (baseline value) | Week 4, Week 8, Week 12 | 
| Relative Change in BSA After 4, 8 and 12 Weeks of Therapy With BCD-085 | The area of skin affected by psoriasis (BSA) is estimated with the palm rule. The area of the human palm without fingers corresponds to about 1% of the body surface. Relative (percentage) from baseline is calculated as 100 x (baseline value - time point t value) / (baseline value). If the value decreases from baseline it means improvement. | Week 4, Week 8, Week 12 | 
| Relative Change in NAPSI Score After 12 Weeks of Therapy With BCD-085 | The NAPSI is used to assign a score to each nail involved, which can vary from 0 to 8. In this study, nail involvement will be assessed only for hands, so the total index of all nails can be from 0 to 80 (only hands). A negative change from baseline indicates improvement. Relative (percentage) change in NAPSI score from baseline (screening) is calculated as 100 x (baseline value - time point t value) / (baseline value) | Week 12 | 
| Mean Change in Severity of Pruritus Assessed by Visual Analog Scale After 1, 4, 8 and 12 Weeks of Treatment With BCD-085 | Mean change in severity of pruritus assessed by visual analog scale (from 0 (no itch) to 100 mm (unbearable itch)) after 1, 4, 8 and 12 weeks of treatment with BCD-085 | Week 1, Week 4, Week 8, Week 12 | 
| Number of Patients With sPGA Response After 4, 8, 12 Weeks of Treatment With BCD-085 | The sPGA scale is used to assess the psoriatic lesions in a certain patient from 0 (clear) to 5 (very severe). Within each area, the severity is estimated by three criteria (induration, desquamation, and erythema). | Week 4, Week 8, Week 12 | 
| Mean Change in Quality of Life Assessed by SF-36 After 4, 8 and 12 Weeks of Treatment With BCD-085 | SF-36 is a standardized participant-administered measure designed to evaluate 8 domains of functional health and well being with 2 components (physical health score [PH] and mental component score [MH]). Both scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. | Week 4, Week 8, Week 12 | 
| Mean Change in Quality of Life Assessed by DLQI After 4, 8 and 12 Weeks of Treatment With BCD-085 | The Dermatology Life Quality Index (DLQI) is a 10-item self-reported survey, which addresses feelings, daily activities, leisure, work, school, personal relationships, and treatment. Each question was assessed using a 3-point scale, where score 3 means very much, score 2 means a lot, score 1 - a little, and score 0 - not at all. If more than two questions were left unanswered, the questionnaire was considered invalid. A total score was calculated by summing the score of all items (total maximum score is 30; total minimum score is 0). The higher score representing greater health-related quality of life impairment. The mean score change was estimated as the difference between the DLQI at baseline and at the assessed visit (the baseline score was subtracted from the visit score). | Week 4, Week 8, Week 12 | 
| Frequency of AE/SAE | Number of participants with AEs and SAEs was presented. The analysis was performed on safety Population which comprised of all participants who received at least one dose of study treatment. | 14 weeks | 
| Frequency of Local Reactions | Number of participants with local reactions was presented. The analysis was performed on safety Population which comprised of all participants who received at least one dose of study treatment. | 14 weeks | 
| Frequency of AE/SAE Grade 4 CTCAE 4.03 | Number of participants with AEs/SAEs grade 4 CTCAE 4.03 was presented. The analysis was performed on safety Population which comprised of all participants who received at least one dose of study treatment. | 14 weeks | 
| Frequency of Withdrawal Due to AE/SAE | Number of participants who withdrew due to AEs/SAEs was presented. The analysis was performed on safety Population which comprised of all participants who received at least one dose of study treatment. | 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interleukin 17, monoclonal antibody, psoriasis