An International Multicenter, Randomized, Double-blind, Placebo-Controlled Clinical Study of Efficacy and Safety of Two Dosing Regimens of BCD-085 (JSC BIOCAD, Russia) in Patients With Moderate to Severe Plaque Psoriasis

An International Multicenter, Randomized, Double-blind, Placebo-Controlled Clinical Study of Efficacy and Safety of Two Dosing Regimens of BCD-085 (JSC BIOCAD, Russia) in Patients With Moderate to Severe Plaque Psoriasis

BCD-085 is an innovative drug, a monoclonal antibody against interleukin-17. The toxicity, safety, and pharmacokinetics of BCD-085 were investigated in animals, in phase I clinical study in healthy volunteers, and in phase III clinical study in patients with moderate to severe plaque psoriasis. This clinical study aims at investigating the efficacy and safety of BCD-085 every other week regimen (after induction for the first 3 weeks) versus BCD-085 one per month regimen (after induction for first 3 weeks) versus placebo in patients with moderate to severe plaque psoriasis.

Study purpose:

To investigate the efficacy and safety of BCD-085 versus placebo in patients with moderate to severe plaque psoriasis (psoriasis vulgaris)

Study objectives:

1. To compare the efficacy of BCD-085 every 2 weeks versus BCD-085 every 4 weeks versus placebo, based on the proportion of patients who achieved a PASI75, target sPGA score, and on other secondary efficacy measures.
2. To evaluate the proportion of patients in each study arm who develop adverse events with multiple injections of BCD-085 and placebo. Compare the safety profiles of BCD-085 when used every 4 weeks and when used every 2 weeks.
3. 4. To assess the immunogenicity of BCD-085 defined as the proportion of patients who develop anti-drug antibodies (binding or neutralizing).

Inclusion Criteria:

1. Subjects must give a written and signed informed consent.
2. Men or women at least 18 years old at the time of signing the ICF
3. Moderate to severe plaque psoriasis diagnosed at least 6 months before signing the informed consent form.
4. Patients received at least one course of phototherapy or systemic therapy for psoriasis or are candidates for such treatment according to the investigator.
5. Body surface area (BSA) affected by psoriasis of 10% or greater, the PASI score of 10 or greater, and the sPGA score of 3 or greater at screening.
6. Negative pregnancy urine test in female subjects (no test is required in women who are post-menopausal for at least 2 years and in surgically sterile women).
7. The patient must be able to follow the Protocol procedures (in the investigator's opinion).
8. Patients of childbearing potential and their partners with preserved reproductive function must implement reliable contraceptive methods starting from signing informed consent to 20 weeks after the last dose of the study therapy. This requirement does not apply to the patients after surgical sterilization and to females who are post-menopausal for 2 years or longer. Reliable contraception methods suggest using one barrier method in combination with one of the following: spermicides, intrauterine device/oral contraceptives

Exclusion Criteria:

1. Baseline erythrodermic, pustular, and guttate psoriasis or any other skin diseases (e.g. eczema) that can affect/complicate assessment of psoriasis treatment

2. Use of the following medications:

   • Prior use of monoclonal antibodies targeting IL17 or its receptor
   • Prior use of more than one drug containing monoclonal antibodies or their fragments
   • Prior use of monoclonal antibodies within 12 weeks before signing the informed consent.
   • Any systemic medications for psoriasis (including glucocorticoids, methotrexate, sulfasalazine, cyclosporine, acitretin, mycophenolate mofetil, аpremilast, calcitriol derivatives, etc.) used within 4 weeks before signing the ICF If prior systemic therapy with non-biologics was stopped due to any reasons, the screening period can be extended up to 8 weeks during which no new non-biologics are allowed.
   • Use of phototherapy within 4 weeks before signing the ICF
   • Topical medications for psoriasis used within 2 weeks before signing the ICF
   • Vaccination with live or attenuated vaccines within 8 weeks before signing the ICF

3. Any active systemic infection or recurrent infection at screening/randomization

4. HIV, hepatitis B, hepatitis C, or syphilis

5. Blood biochemistry abnormalities appearing as:

   1. baseline creatinine > 2 × ULN
   2. baseline ALT, AST or alkaline phosphatase > 2.5 × ULN
   3. baseline bilirubin > 1.5 × ULN

6. WBC count < 3.0 × 109/L; ANC < <2.0× 109/L; platelet count < 100 × 109/L, or hemoglobin < 90 g/L at baseline

7. Any psychiatric conditions including severe depressive disorders and/or any history of suicidal thoughts or suicidal attempts ;

8. Signs of clinically significant depression (Beck's score of 16 or more at screening)

9. Alcohol or substance abuse

10. Tuberculosis now or in the past

11. Latent TB infection (positive results of the Diaskintest or QuantiFERON test, or T-spot).

12. Concurrent diseases ongoing at screening that may increase the risk of adverse events during the study or affect the evaluation of psoriasis symptoms (mask, enhance or alter the symptoms of psoriasis, or cause clinical or laboratory signs/symptoms similar to those of psoriasis):

    • active inflammatory diseases or aggravation of chronic inflammatory diseases other than psoriasis
    • Stable angina class III-IV, unstable angina or a history of myocardial infarction within 1 year before signing the informed consent
    • Cardiac failure moderate to severe (NYHA class III-IV)
    • Treatment-resistant hypertension
    • A history of severe asthma or angioedema
    • Moderate to severe respiratory failure, COPD grade ¾
    • Diabetes mellitus with unsatisfactory glycemic control, when the level of glycated hemoglobin HbA1С ≥8% (results are valid if the test was performed at the screening or within 3 months before signing the ICF)
    • The patient has thyrotoxicosis, which persists in the presence of thyreostatic medications, or hypothyroidism despite of the thyroid hormone treatment
    • Systemic autoimmune diseases (including but not limited to SLE, rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed connective tissue disease , intersection syndrome, etc.)
    • Any other underlying conditions (including but not limited to metabolic, hematologic, hepatic, renal, pulmonary, neurological, endocrine, cardiac, gastrointestinal conditions and infections) that, in the opinion of the investigator, may affect the course of psoriasis, affect the assessment of signs/symptoms of psoriasis, or put patients using the study treatment at additional risk

13. Malignancies with less than 5 years of remission

14. Known severe allergies (anaphylaxis or drug allergy to two or more drug products)

15. Known allergy or intolerance to monoclonal antibody drugs (murine, chimeric, humanized, or human) or any other components of the test drug or comparator

16. Major surgery within 30 days before the screening, or a major surgery being scheduled at any time during the study

17. Severe infections (including those that required hospitalization or parenteral antibacterial/antimycotic/antiprotozoal treatment) within 6 months before signing the ICF

18. Systemic antibacterial/antimycotic/antiprotozoal treatment within 2 months before the signing the ICF

19. More than 4 episodes of respiratory infection within 6 months before signing the ICF

20. Episodes of severe mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, etc.) within 6 months before signing the ICF

21. A history of epileptic attacks or seizures

22. Any concurrent diseases during which, in the investigator's opinion, the study treatment can harm the patient

23. Pregnancy, breastfeeding, or planning for pregnancy while participating in the study

24. Participation in any other clinical study within 3 months before signing the ICF or simultaneous participation in other clinical studies

25. Patients will not be re-enrolled in this study if they were randomized to this study and then discontinue the participation