Open Label Study of Tolerability, Pharmacokinetics and Pharmacodynamics of BCD-054 (Pegylated Interferon Beta-1a), IM and SC, Compared to Rebif® and Avonex® in Healthy Volunteers

Study Overview
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Brief Summary
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This is an international multicenter study of tolerability, pharmacokinetics and pharmacodynamics of drug product BCD-054 (CJSC BIOCAD, Russia), administrated intramuscular and subcutaneous, compared to Rebif® (Merck Serono S.p.A., Italy) and Avonex® (Biogen Idec Ltd, UK) in healthy volunteers. The study involves 2 stages - single ascending dose administration and multiple estimated therapeutic dose administration of BCD-054.

Conditions
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Healthy

Intervention / Treatment
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* Drug: BCD-054
* Drug: Rebif
* Drug: Avonex


Participation Criteria
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Eligibility Criteria
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InInclusion Criteria: Written informed consent; Male gender; Age 18 - 45 years inclusive; Body mass index (BMI) (18,5 - 24,99 kg/m2); Healthy condition proven by the volunteer's history, global assessment and laboratory analysis results: Absence in past medical history and at screening of clinically significant dysfunctions of circulatory, respiratory, nervous, hematopoietic, endocrine and digestive systems, liver and kidneys; No history of cardiovascular diseases and diseases of the thyroid gland Haematology and biochemistry tests, urinalysis and thyroid hormone analysis results are within normal limits according to standards of the study site. Screening laboratory analyses should be performed not more than 14 days before volunteer's inclusion in the study; Hemodynamic parameters are within normal limits: systolic blood pressure - from 100 to 139 mmHg, diastolic blood pressure - from 60 to 90 mmHg, heart rate - from 50 to 90 bpm; Absence of history of chronic infection (tuberculosis) and chronic inflammation; Absence of HIV, hepatitis B and C virus, syphilis; Absence of acute infections within 4 weeks before inclusion in the study; Absence of psychiatric disorders and other conditions that can interfere with volunteer's ability to follow the study protocol, including depression; Well-being (in volunteer's opinion) within 30 days before participation in the study; Absence of history of systematic alcohol and drug abuse; Ability of the volunteer, in investigator's opinion, to follow the study protocol procedures and requirements; Willingness of volunteers and their sexual partners of childbearing potential to use reliable contraception methods starting from 2 weeks before inclusion into the study and until 4 weeks after receiving the last dose of the investigational products. This criterion is not applicable to patients who underwent surgical sterilization. Reliable contraceptive measures include one barrier method in combination with one of the following methods: spermicides, intrauterine device or oral contraceptives used by participant's partner; Consent to avoid alcohol intake within 24 hours before and 8 days after each administration of the test or reference drugs; Consent to avoid grapefruit juice (or other products containing grapefruit) intake within 72 hours before and 8 days after each administration of the study or reference drugs. Exclusion Criteria: Previous use of IFN-β1-containing medications at any time before inclusion; History of serious allergic reactions (anaphylaxis or multiple allergy); Known allergy or intolerance to interferons or any other components of study or reference drugs or pegylated proteins; Major surgery within 30 days before screening; Impossibility to install venous catheter for blood sampling (e.g. because of skin disorders at the sites of venipuncture); Diseases or other conditions that can interfere with the investigational drugs pharmacokinetics (e.g. chronic liver, kidney, blood, circulatory system, lung or neuroendocrine diseases, including diabetes mellitus and others); History of fever over 40°С History of increase in aminotransferases (ALT, AST) > 2.5 × ULN History of epileptic seizures; Depression and/or suicidal ideas, suicide attempts in history Regular oral or parenteral use of any medications including over-the-counter drugs, vitamins and nutritional additives within less than 2 weeks before inclusion in the study; Intake of medications, including over-the-counter drugs and biologically active additives that can influence hemodynamics, liver function etc. (barbiturates, omeprazole, cimetidine etc.) within less than 30 days before inclusion in the study; Intake of medications that influence immune status (cytokines and their inductors, glucocorticoids etc.) within less than 30 days before inclusion in the study; Vaccination within 4 weeks prior to inclusion Smoking more than 10 cigarettes per day; Subjects who consume more than 10 units of alcohol per week or who have history of alcohol abuse or evidence of drug/chemical abuse (one unit of alcohol equals ½ l [500 ml] of beer, one glass [200 ml] of wine or l shot glass [50 ml] of spirits); Donation of 450 ml and more of blood or plasma within 2 months before inclusion in the study; Participation in other clinical studies within less than 1 month before inclusion in the study or simultaneous participation in another clinical study; Previous participation in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-054<br>Pegylated interferon beta 1a Single doses - 60 mcg, SC/IM Single doses - 120 mcg, SC/IM Single doses - 240 mcg, SC/IM Single doses - 360 mcg, SC/IM Multiple doses - 180 mcg, SC/IM | Drug: BCD-054<br> <br> * Other names: pegylated interferon beta 1a;|
| Active Comparator: Rebif<br>interferon beta 1a 44 mcg, SC, 3 times a week for 2 weeks | Drug: Rebif<br> <br> * Other names: interferon beta 1a;|
| Active Comparator: Avonex<br>interferon beta 1a 30 mcg, IM, once a week for 2 weeks | Drug: Avonex<br> <br> * Other names: interferon beta 1a;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-168); AUC (0-336); AUC (0-672); AUC (0-∞ ) of Interferon (IFN) Beta-1a | Stage 1 primary outcome measure for pharmacokinetics analysis. Area under concentration-time curve (AUC) of interferon (IFN) beta-1a from the moment of drug administration up to 168, 336, 648 hours respectively | 0 to 168 hours; 0 to 336 hours; 0 to 672 hours respectively | 
| AUC(0-last); AUC (0-∞ ) BCD-054 of Interferon (IFN) Beta-1a - 180 mcg - SC, BCD-054 - 180 mcg - IM | Stage 2 primary outcome measure for pharmacokinetics analysis. Area under concentration-time curve (AUC) of interferon (IFN) beta-1a from the moment of drug administration until last quantifiable concentration | 0 to 672 hours | 
| AUC (0-168); AUC (0-336); AUC (0-672);AUC (0-∞ ) of Neopterin | Stage 1 primary outcome measure for pharmacodynamics analysis. Area under concentration-time curve (AUC) of neopterin from the moment of drug administration until 168, 336, 648 hours respectively | 0 to 168 hours; 0 to 336 hours; 0 to 672 hours respectively | 
| AUC(0-∞), AUC(0-last) of Neopterin | Stage 2 primary outcome measure for pharmacodynamics analysis. Area under concentration-time curve (AUC) of neopterin from the moment of drug administration until last quantifiable concentration | 0 to 672 hours | 
| Adverse Event (AE) and Serious Adverse Event (SAE) Incidence | Stage 1 | 4 weeks | 
| Adverse Event (AE) and Serious Adverse Event (SAE) Incidence BCD-054 - 180 mcg - SC/IM | Stage 2 BCD-054 - 180 mcg - SC/IM | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pegylated interferon beta, Volunteers