Clinical trial NCT02888106: Myrcludex B in Combination With Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients With Chronic Viral Hepatitis B With Delta-agent
Official title: A Multicenter, Open-label, Randomised, Comparative, Parallel-Arm, Phase II Study to Assess Efficacy and Safety of Myrcludex B in Combination With Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients With Chronic Viral Hepatitis B With Delta-agent
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Viral Hepatitis B With Delta-agent
Lead sponsor: Hepatera Ltd.
Sponsor class: INDUSTRY
First posted: 2016-09-02
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, Open-label, Randomized, Comparative, parallel-arm phase II study
Primary purpose: TREATMENT

Brief summary: Randomised, Comparative, Parallel-Arm Study to Assess Efficacy and Safety of Myrcludex B in Combination with Peginterferon Alfa-2a Versus Peginterferon Alfa-2a Alone in Patients with Chronic Viral Hepatitis B with Delta-agent

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent form.
2. Males and females 18 to 65 years of age (inclusively).
3. Patients with chronic hepatitis B (HBeAg-positive or negative) and HBsAg-positive for at least 6 months prior to Screening.
4. Positive for anti-HDV antibodies for at least 6 months prior to Screening.
5. HDV RNA-positive at Screening.
6. ALT ≥ 1 x ULN and \< 10 x ULN.
7. 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:

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

   1. Hemoglobin \< 100 g/L
   2. Leucocytes \< 3000/µL
   3. Neutrophils \< 1500/µL
   4. Platelets \< 90000/µL
   5. Serum creatinine \>1.5 x ULN.
7. 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.
8. 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.
9. HCV or HIV coinfection (patients with anti-HCV antibodies and no HCV RNA at Screening are eligible).
10. Hepatocellular carcinoma.
11. 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).
12. Contraindications for liver biopsy.
13. Concurrent malignancy (current diagnosed or suspected malignancy; risk of a previous malignancy recurrence).
14. Severe decompensated cardiovascular diseases, including unstable and poorly controlled conditions, over 6 months before Screening.
15. History of poorly controlled thyroid conditions or clinically significant signs of thyroid dysfunction at Screening.
16. Previous or current severe renal failure or significant renal dysfunction at Screening.
17. Previous or current chronic pulmonary disease with respiratory distortion at Screening.
18. Previous or current severe retinopathy, significant ophthalmology disorders associated with diabetes mellitus or hypertension.
19. Previous or current severe psychiatric disorders at Screening (e.g. severe depressions, suicidal attempts, severe neuroses or cognitive disorders).
20. Previous or current endocrine disorders (hypoglycaemia, hyperglycaemia, diabetes mellitus) that are not adequately controlled at Screening.
21. History of visceral organ transplantation.
22. 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.
23. History of immune disorders (e.g. idiopathic thrombocytopenic purpura, lupus erythematosus, sclerodermia, severe psoriasis, rheumatoid arthritis).
24. Need for concomitant use of glucocorticoids or myelotoxic agents.
25. Participation in another clinical study within 30 days prior to enrollment into this study.
26. Pregnant or breast-feeding females.
27. Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study.

Primary outcomes:
measure: Percentage of Patients With Negative HDV RNA by PCR
timeFrame: 72 weeks
Secondary outcomes:
measure: Percentage of Patients With Negative HDV RNA by PCR
timeFrame: 24 and 48 weeks
measure: Percentage of Patients With Normalized ALT
timeFrame: 24, 48 and 72 weeks
measure: Percentage of Patients With Combined Response
timeFrame: 24, 48 and 72 weeks
measure: Percentage of Patients With HВsAg Response
timeFrame: 24, 48 and 72 weeks
measure: Percentage of Patients With HBsAg Negativation
timeFrame: 48 and 72 weeks
measure: Percentage of Patients With Negative HBV DNA by PCR
timeFrame: 24, 48 and 72 weeks
measure: The Intensity of Liver Fibrosis Based on Results of Transient Elastometry of Liver at Weeks 48 and 72.
timeFrame: 48 and 72 weeks
measure: Number of Participants With Change (Improvement / Worsening) in Fibrosis and Histological Activity Stage From Baseline to Post-treatment
timeFrame: 72 weeks
measure: Change in Molecular Analyses of Relative HDV RNA Expression, Relative HBV Pregenomic Expression, Relative Total HBV RNA Expression (X Region), Relative HBV RNA Expression (S Region).
timeFrame: 48 and 72 weeks
measure: Change in Molecular Analyses of Total HBV DNA (X Region) Copies/Cell, HBV DNA (S Region) Copies/Cell, cccDNA Copies/Cell From Baseline to Post-treatment.
timeFrame: 48 and 72 weeks
measure: Change in Molecular Analysis of HDAg Positive Hepatocytes (%) From Baseline to Post-treatment
timeFrame: 48 and 72 weeks
measure: Change in the Gene Expression Analyses From Baseline to Post-treatment
timeFrame: Weeks 48 - 72
Other outcomes:
Locations:
city: Chelyabinsk
country: Russian Federation
facility: State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare
city: Krasnodar
country: Russian Federation
facility: State Budgetary Institution of healthcare "Specialized Clinical Infectious Diseases Hospital" Ministry of Health
city: Moscow
country: Russian Federation
facility: Moscow Regional Research and Clinical Institute
city: Moscow
country: Russian Federation
facility: Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance
city: Moscow
country: Russian Federation
facility: LLC "Clinic of Modern Medicine"
city: Samara
country: Russian Federation
facility: Medical Company "Gepatolog" LLC
city: Stavropol'
country: Russian Federation
facility: State Budgetary Institution of healthcare 'Stavropol regional clinical hospital'
Study officials:
affiliation: Moscow Regional Research and Clinical Institute (MONIKI)
name: Pavel Bogomolov, PhD
role: PRINCIPAL_INVESTIGATOR
References: