Myrcludex B in Combination With Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients With Chronic Viral Hepatitis B With Delta-agent

This is a multicenter, open-label, randomised, comparative, active-controlled parallel-arm phase II study.

The study will be conducted in Russia. The aim of this study is to explore the safety and efficacy of treatment with Myrcludex B used as a monotherapy and in combination with PEG-IFNα and Tenofovir compared to monotherapy with PEG-IFNα in patients with chronic viral hepatitis B with delta-agent, based on the achievement of undetectable viral load at the end of the follow-up period 6 months (24 weeks) after the end of treatment. The study is also aimed at investigating immunogenicity of Myrcludex B and the drug pharmacokinetics when used in combination with PEG IFN alfa-2a and with Tenofovir.

It is planned to screen 110 patients, and 90 patients will be randomised in equal numbers into six treatment arms.

• Arm A (n=15): PEG IFN alfa-2a 180 µg for 48 weeks
• Arm B (n=15): Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks
• Arm C (n=15): Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks
• Arm D (n=15): Myrcludex B 2 mg for 48 weeks
• Arm E (n=15): Myrcludex B 10 mg (10 mg once a day)+ PEG IFN alfa-2a 180 µg for 48 weeks
• Arm F (n=15): Myrcludex B 10 mg (5 mg twice a day)+ Tenofovir for 48 weeks

Inclusion criteria

• Signed Informed Consent form.
• Males and females 18 to 65 years of age (inclusively).
• Patients with chronic hepatitis B (HBeAg-positive or negative) and HBsAg-positive for at least 6 months prior to Screening.
• Positive for anti-HDV antibodies for at least 6 months prior to Screening.
• HDV RNA-positive at Screening.
• ALT ≥ 1 x ULN and < 10 x ULN.
• The patient agreed to use adequate method of contraception during the study, starting from the time of Informed Consent signing and until completion of the Follow-up Period.

Exclusion criteria

• Intolerance or hypersensitivity to the active ingredient or other components of the study drug Myrcludex B.
• Intolerance or hypersensitivity to interferons alfa, genetically engineered E.coli medications, polyethylene glycol or other components of peginterferon alfa-2a.
• Previous treatment with Myrcludex B (patients with previous exposure to interferon are eligible).
• Therapy with antiviral drugs for chronic viral hepatitis B with delta-agent over the previous 6 months.
• Therapy with anti-tumour agents (including radiotherapy) or immunomodulatory medications (including systemic glucocorticoids) over the previous 6 months.
• The following laboratory test results at Screening:

• Hemoglobin < 100 g/L
• Leucocytes < 3000/µL
• Neutrophils < 1500/µL
• Platelets < 90000/µL
• Serum creatinine >1.5 x ULN.
• Total bilirubin > 34.2 µM/L. Patients with higher total bilirubin may be enrolled upon consultation with the study Medical Monitor, if there is clear evidence that the elevated bilirubin is caused by Gilbert's syndrome.
• Current or previous decompensated liver disease, including coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminaemia, ascites, and oesophageal varices haemorrhage; Child-Pugh score of B/C or ≥6 points.
• HCV or HIV coinfection (patients with anti-HCV antibodies and no HCV RNA at Screening are eligible).
• Hepatocellular carcinoma.
• Signs of drug- or alcohol-induced liver disease or any other medical conditions associated with chronic liver disease (e.g. autoimmune hepatitis, hemochromatosis, thalassaemia, alcoholic hepatitis, toxic liver disease).
• Contraindications for liver biopsy.
• Concurrent malignancy (current diagnosed or suspected malignancy; risk of a previous malignancy recurrence).
• Severe decompensated cardiovascular diseases, including unstable and poorly controlled conditions, over 6 months before Screening.
• History of poorly controlled thyroid conditions or clinically significant signs of thyroid dysfunction at Screening.
• Previous or current severe renal failure or significant renal dysfunction at Screening.
• Previous or current chronic pulmonary disease with respiratory distortion at Screening.
• Previous or current severe retinopathy, significant ophthalmology disorders associated with diabetes mellitus or hypertension.
• Previous or current severe psychiatric disorders at Screening (e.g. severe depressions, suicidal attempts, severe neuroses or cognitive disorders).
• Previous or current endocrine disorders (hypoglycaemia, hyperglycaemia, diabetes mellitus) that are not adequately controlled at Screening.
• History of visceral organ transplantation.
• Signs of drug and/or alcohol dependence (80 g of alcohol/day for men and 40 g of alcohol/day for women) within 1 year before Screening.
• History of immune disorders (e.g. idiopathic thrombocytopenic purpura, lupus erythematosus, sclerodermia, severe psoriasis, rheumatoid arthritis).
• Need for concomitant use of glucocorticoids or myelotoxic agents.
• Participation in another clinical study within 30 days prior to enrollment into this study.
• Pregnant or breast-feeding females.
• Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study.