Comparative Clinical Trial of Efficacy and Safety of BCD-057 and Humira® in Patients With Moderate to Severe Plaque Psoriasis

International Multi-center Comparative Randomized Double-blind Clinical Trial of Efficacy and Safety of BCD-057 (Adalimumab Produced by BIOCAD, Russia) and Humira® (Adalimumab Produced by Vetter Pharma-Fertigung Gmbh & Co KG, Germany) in Patients With Moderate to Severe Plaque Psoriasis

CALYPSO clinical study is a phase 3 study which is carried out to establish the efficacy, safety and pharmacokinetic equivalence of BCD-055 (adalimumab, manufactured by JSC BIOCAD, Russia) and Humira® when used in patients with moderate to severe plaque psoriasis.

CALYPSO study is the next step of clinical evaluation of adalimumab biosimilar manufactured by joint-stock company (JSC) BIOCAD, Russia.The aim of this study is to establish that BCD-057 is equivalent to Humira® in terms of efficacy, safety and pharmacokinetics when used by the standard regimen in patients with plaque psoriasis.

The study will enroll 344 patients with moderate to severe plaque psoriasis, who will be randomized into 2 groups (1:1 ratio): patients from the first group will receive BCD-057 subcutaneously (SC) at a dose 80 mg on week 0, then at a dose 40 mg on weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23. Then participants of this group will be invited for randomization at week 25 (in order to keep the double-blind design of the study), but it will have a formal character (assignment of a new randomization number and lot). Patients will continue to receive 40 mg of BCD-057 on weeks 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and 51.

Patients from the second group will receive Humira® subcutaneously (SC) at a dose 80 mg on week 0, then at a dose 40 mg on weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23. At week 25 participants will re-randomized (1:1) to treatment with Humira® or will transitioned to BCD-057.They will receive Humira® or BCD-057 at a dose 40 mg on weeks 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and 51.

Inclusion Criteria:

• Patient had written informed consent.
• Age between 18 and 75 years.
• Patient has moderate to severe plaque psoriasis with stable course of the disease for 6 months
• Patient has had at least 1 course of phototherapy or systemic treatment for psoriasis or are candidates for such treatment in opinion of Investigator.
• BSA affected by psoriasis ≥ 10%, PASI score ≥ 12, sPGA score ≥ 3.
• Patient has hemoglobin ≥ 10 g/dl, leucocytes count ≥ 3 000/mcl, thrombocytes count ≥ 100 000/mcl, neutrophil count ≥ 2 000/mcl, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase exceed 2,5 or less times the upper limit of the normal range creatinine less than 176,8 µmol/l, no serologic or virologic markers of hepatitis B virus and hepatitis C virus, negative urine pregnancy test, no signs of tuberculosis (negative tuberculosis skin test or negative quantiferon test. Patients can be included in they have positive tuberculin test, have had Bacteria Calmette-Guerin (BCG) vaccination and have negative Diaskintest or negative quantiferon test. Patients can be included if they have positive tuberculin test, have not been vaccinated with BCG and also patients with positive or uncertain quantiferon test/Diaskintest if they have documented adequate prophylaxis of tuberculosis finished before first adalimumab injection AND have documented absence of contacts with patients who have active tuberculosis AND have no signs of tuberculosis on chest X-Ray that was performed during 3 months before randomization)
• 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 adalimumab, history of use of any other biological anti-tumor necrosis factor-alpha therapy. Prior use of two or more biologics for treatment of psoriasis.
• Previous receipt of monoclonal antibodies if they were cancelled less that in 12 weeks before screening
• Patient is taking corticosteroids for up to 4 weeks before signing informed consent and during screening, disease-modifying drugs including methotrexate, sulfasalazin and cyclosporin for up to 4 weeks before signing informed consent, leflunomide, cyclophosphamide for up to 6 months before signing informed consent, phototherapy including selective phototherapy and photochemotherapy for up to 4 weeks before signing informed consent, live or attenuated vaccines for up to 8 weeks before signing informed consent.
• Subject cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot avoid phototherapy.
• Subject has a planned surgical intervention during the study or had surgical intervention less than 30 days prior to study.
• Subject has an active infection or history of infections as follows: any active infection for which systemic anti-infectives were used within 28 days prior to signing informed consent; a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to signing informed consent; recurrent or chronic infections or other active infection that, in the opinion of the Investigator, might cause this study to be detrimental to the subject.
• Subject has known history of human immunodeficiency virus or any other severe immunodeficiency.
• Hepatitis B surface antigen or Hepatitis B core antigen or Hepatitis C antibody positivity at screening.
• History of tuberculosis.
• Positive results of rapid plasma reagin-test for T.pallidum at screening.
• Active ongoing diseases other than psoriasis that might confound the evaluation of the benefit of treatment of adalimumab or can increase risk of adverse reactions: acute inflammatory diseases or exacerbation of chronic diseases otherwise than psoriasis; stable ischemic heart disease III-IV functional class, unstable angina or history of myocardial infarction less than 1 year before the signing of informed consent; moderate to severe heart failure (New York Heart Association [NYHA] class III/IV; severe resistant arterial hypertension, atopic bronchial asthma, history of angiooedema, moderate to severe respiratory insufficiency, chronic obstructive lung disease 3-4 grade, decompensated diabetes mellitus, systemic autoimmune diseases, active neurologic disorders or their symptoms, other underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.
• Subject has history of malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma.
• Subject has a history of hypersensitivity to the active substance or to any of the excipients of adalimumab or BCD-057 or other monoclonal antibodies.
• Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
• Subject has any mental illness, including severe depressive disorders and / or suicidal thoughts in history, which, in the opinion of the investigator, may create excessive risk to the patient or to influence the patient's ability to follow the protocol.
• History of drug addiction, alcoholism.
• Simultaneous participation in any other clinical trial, as well as former participation in other clinical trials within 3 months before this study initiation; previous participation in this study.