Back to results

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

Primary Purpose

Chronic Viral Hepatitis B With Delta-agent

Status

Completed

Phase

Phase 2

Locations

Russian Federation

Study Type

Interventional

Intervention

Myrcludex B

PEG IFN alfa-2a

Tenofovir

About this trial

This is an interventional treatment trial for Chronic Viral Hepatitis B With Delta-agent

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
1. Hemoglobin < 100 g/L
2. Leucocytes < 3000/µL
3. Neutrophils < 1500/µL
4. Platelets < 90000/µL
5. 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.

Sites / Locations

State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare
State Budgetary Institution of healthcare "Specialized Clinical Infectious Diseases Hospital" Ministry of Health
Moscow Regional Research and Clinical Institute
Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance
LLC "Clinic of Modern Medicine"
Medical Company "Gepatolog" LLC
State Budgetary Institution of healthcare 'Stavropol regional clinical hospital'

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm C

Arm D

Arm E

Arm F

Arm Description

PEG IFN alfa-2a 180 µg for 48 weeks

Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks

Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks

Myrcludex B 2 mg for 48 weeks

Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks

Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks

Outcomes

Primary Outcome Measures

Percentage of Patients With Negative HDV RNA by PCR

Negativation of HDV RNA by PCR (undetectable HDV RNA) at Week 72 (end of follow-up period)

Secondary Outcome Measures

Percentage of Patients With Negative HDV RNA by PCR

Percentage of patients with negative HDV RNA by PCR (undetectable HDV RNA) at Weeks 24 and 48

Percentage of Patients With Normalized ALT

Percentage of patients with normalized ALT at Weeks 24, 48 and 72. ALT normalisation was defined as having an ALT value within the normal range (≤31 U/L for females and ≤41 U/L for males)

Percentage of Patients With Combined Response

Combined response is defined as negative HDV RNA and ALT normalization at Weeks 24, 48, and 72. The criteria for combined response were HDV RNA value below LLoD (where LLoD=10 IU/ml) and ALT within normal range (≤31 U/L for females and ≤41 U/L for males)

Percentage of Patients With HВsAg Response

HВsAg response was defined as HBsAg negativation or > 1 log10 IU/mL decline from baseline.

Percentage of Patients With HBsAg Negativation

Undetectable HВsAg with appearance of HbsAg antibodies or without it.

Percentage of Patients With Negative HBV DNA by PCR

Percentage of patients with undetectable HBV DNA by PCR at Weeks 24, 48 and 72

The Intensity of Liver Fibrosis Based on Results of Transient Elastometry of Liver at Weeks 48 and 72.

Change in liver stiffness and intensity of liver fibrosis based on results of transient elastometry of liver at weeks 48 and 72.

Number of Participants With Change (Improvement / Worsening) in Fibrosis and Histological Activity Stage From Baseline to Post-treatment

Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results from baseline to post-treatment Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available.

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).

Molecular analyses of relative HDV RNA expression, relative HBV pregenomic expression, relative total HBV RNA expression (X region), relative HBV RNA expression (S region) from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

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.

Molecular analyses of total HBV DNA (X region) copies/cell, HBV DNA (S region) copies/cell, cccDNA copies/cell from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

Change in Molecular Analysis of HDAg Positive Hepatocytes (%) From Baseline to Post-treatment

Molecular analysis of HDAg positive Hepatocytes (percentage of HDAg positive Hepatocytes) from baseline to post-treatment. *Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

Change in the Gene Expression Analyses From Baseline to Post-treatment

Change in the gene expression analyses of CXCL10, NTCP, CYP7A1, ISG15, MX1, OAS, HLA-E, TAP1 and USP18 from baseline to post-treatment. Biopsy post treatment performed at Week 48 for arm D:MXB 2mg and arm F:MXB 5mg bid + Tenofovir, and performed at Week 72 for arms A:PEG-IFN, B:MXB 2mg + PEG-IFN, C:MXB 5mg + PEG-IFN and arm E:MXB 10mg + PEG-IFN.

Full Information

NCT ID

NCT02888106

First Posted

August 30, 2016

Last Updated

April 7, 2021

Sponsor

Hepatera Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02888106

Brief Title

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

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

April 2016 (Actual)

Primary Completion Date

November 22, 2019 (Actual)

Study Completion Date

October 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hepatera Ltd.

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Viral Hepatitis B With Delta-agent

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Multicenter, Open-label, Randomized, Comparative, parallel-arm phase II study

Masking

None (Open Label)

Allocation

Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

PEG IFN alfa-2a 180 µg for 48 weeks

Arm Title

Arm B

Arm Type

Experimental

Arm Description

Myrcludex B 2 mg + PEG IFN alfa-2a 180 µg for 48 weeks

Arm Title

Arm C

Arm Type

Experimental

Arm Description

Myrcludex B 5 mg + PEG IFN alfa-2a 180 µg for 48 weeks

Arm Title

Arm D

Arm Type

Experimental

Arm Description

Myrcludex B 2 mg for 48 weeks

Arm Title

Arm E

Arm Type

Experimental

Arm Description

Myrcludex B 10 mg (10 mg once a day) + PEG-IFN alfa-2a 180 μg during 48 weeks

Arm Title

Arm F

Arm Type

Experimental

Arm Description

Myrcludex B 10 mg (5 mg twice a day) + Tenofovir during 48 weeks

Intervention Type

Drug

Intervention Name(s)

Myrcludex B

Other Intervention Name(s)

Bulevirtide

Intervention Description

Lyophilised powder for solution for subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

PEG IFN alfa-2a

Other Intervention Name(s)

Pegasys

Intervention Description

solution for subcutaneous injection, once per week

Intervention Type

Drug

Intervention Name(s)

Tenofovir

Other Intervention Name(s)

Viread

Intervention Description

Film-coated tablets, 300 mg, per os, once daily

Primary Outcome Measure Information:

Title

Percentage of Patients With Negative HDV RNA by PCR

Description

Negativation of HDV RNA by PCR (undetectable HDV RNA) at Week 72 (end of follow-up period)

Time Frame

72 weeks

Secondary Outcome Measure Information:

Title

Percentage of Patients With Negative HDV RNA by PCR

Description

Percentage of patients with negative HDV RNA by PCR (undetectable HDV RNA) at Weeks 24 and 48

Time Frame

24 and 48 weeks

Title

Percentage of Patients With Normalized ALT

Description

Percentage of patients with normalized ALT at Weeks 24, 48 and 72. ALT normalisation was defined as having an ALT value within the normal range (≤31 U/L for females and ≤41 U/L for males)

Time Frame

24, 48 and 72 weeks

Title

Percentage of Patients With Combined Response

Description

Time Frame

24, 48 and 72 weeks

Title

Percentage of Patients With HВsAg Response

Description

HВsAg response was defined as HBsAg negativation or > 1 log10 IU/mL decline from baseline.

Time Frame

24, 48 and 72 weeks

Title

Percentage of Patients With HBsAg Negativation

Description

Undetectable HВsAg with appearance of HbsAg antibodies or without it.

Time Frame

48 and 72 weeks

Title

Percentage of Patients With Negative HBV DNA by PCR

Description

Percentage of patients with undetectable HBV DNA by PCR at Weeks 24, 48 and 72

Time Frame

24, 48 and 72 weeks

Title

The Intensity of Liver Fibrosis Based on Results of Transient Elastometry of Liver at Weeks 48 and 72.

Description

Change in liver stiffness and intensity of liver fibrosis based on results of transient elastometry of liver at weeks 48 and 72.

Time Frame

48 and 72 weeks

Title

Number of Participants With Change (Improvement / Worsening) in Fibrosis and Histological Activity Stage From Baseline to Post-treatment

Description

Time Frame

72 weeks

Title

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).

Description

Time Frame

48 and 72 weeks

Title

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.

Description

Time Frame

48 and 72 weeks

Title

Change in Molecular Analysis of HDAg Positive Hepatocytes (%) From Baseline to Post-treatment

Description

Time Frame

48 and 72 weeks

Title

Change in the Gene Expression Analyses From Baseline to Post-treatment

Description

Time Frame

Weeks 48 - 72

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pavel Bogomolov, PhD

Organizational Affiliation

Moscow Regional Research and Clinical Institute Moniki n.a. M.F. Vladimirskiy

Official's Role

Principal Investigator

Facility Information:

Facility Name

State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare

City

Chelyabinsk

Country

Russian Federation

Facility Name

State Budgetary Institution of healthcare "Specialized Clinical Infectious Diseases Hospital" Ministry of Health

City

Krasnodar

Country

Russian Federation

Facility Name

Moscow Regional Research and Clinical Institute

City

Moscow

ZIP/Postal Code

129110

Country

Russian Federation

Facility Name

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 Name

LLC "Clinic of Modern Medicine"

City

Moscow

Country

Russian Federation

Facility Name

Medical Company "Gepatolog" LLC

City

Samara

Country

Russian Federation

Facility Name

State Budgetary Institution of healthcare 'Stavropol regional clinical hospital'

City

Stavropol'

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs