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
Condition: Moderate to Severe Plaque Psoriasis
MeSH terms: Psoriasis
Intervention: BCD-085 Q2W; BCD-085 Q4W; Placebo
Intervention description: In Arm 1, the test drug BCD-085 will be used at a dose of 120 mg given as two SC injections according to the following schedule: once a week for the first 3 weeks (induction treatment) and then once every 2 weeks through Week 10.
On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label patients will receive BCD-085 through week 50. The follow-up will continue through week 54.; In Arm 2, and then once every 4 weeks through Week 10. On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 2 will be given BCD-085 once every 4 weeks through week 50. The follow-up will continue through week 54.; In Arm 3, patients will be given two SC injections of placebo (1.0 mL each) according to the following schedule: on Day 1 of weeks 0, 1, 2 and then once every 2 weeks through Week 10.
On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 3 will receive BCD-085 at weeks 12, 13, 14 and then once every 4 weeks through week 50. The follow-up will continue through week 54.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 213.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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