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A Multicenter, Open-label, Randomized Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination With Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients With Chronic Hepatitis D

Primary Purpose

Chronic Hepatitis D Infection With Hepatitis B

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Myrcludex B

Myrcludex-B

Tenofovir

About this trial

This is an interventional treatment trial for Chronic Hepatitis D Infection With Hepatitis B focused on measuring Hepatitis D

Eligibility Criteria

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

Inclusion Criteria:

Age from 18 to 65 years inclusively at the time of signing Informed Consent Form.
Positive serum HBsAg for at least 6 months before Screening.
Positive serum anti-HDV antibody for at least 6 months before screening.
Positive PCR results for serum HDV RNA at Screening.
Patients with liver cirrhosis, irrespective of previous interferon treatment .
Patients without liver cirrhosis, who failed prior interferon treatment or for whom, in the opinion of the Investigator, such treatment is currently contraindicated (including history of interferon intolerance) .
Alanine aminotransferase level >1 x ULN, but less than 10 x ULN.
Previous nucleotide/nucleoside analogue treatment within at least 12 weeks prior to the planned start of study treatment or subject's willingness to take tenofovir for at least 12 weeks prior to the planned start of study treatment.
Negative urine pregnancy test for females of childbearing potential.
Inclusion criteria for female subjects:
- Postmenopausal for at least 2 years, or
- Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or
- Abstinence from heterosexual intercourse throughout the study, or
- Willingness to use highly effective contraception throughout the study and for 3 months after the last dose of the study medication.
Male and female subjects must agree to use a highly effective contraception throughout the study and for 3 months after the last dose of the study medication.
Male subjects must agree not to donate sperm throughout the study and for 3 months after the last dose of the study medication.

Exclusion Criteria:

Child-Pugh score of B-C or over 6 points.
HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative.
Creatinine clearance <60 mL/min.
Total bilirubin ≥ 2mg/dL. Patients with higher total bilirubin values may be included after the consultation with the Study's Medical Monitor, if such elevation can be clearly attributed to Gilbert's syndrome associated with low-grade hyperbilirubinemia.
Any previous or current malignant neoplasms, including hepatic carcinoma.

Sites / Locations

Ifi-Institut für interdisziplinäre Medizin an der Asklepios Klinik St. Georg
Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie
Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie
State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare
State Autonomous Healthcare Institution "Republican Clinical Infectious Diseases Hospital named after Prof. A.F. Agafonov "(SAHI RCID)
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"
Moscow Regional Research Clinical Institute n.a. M.F. Vladimirskiy
State Budget Health Institution of Moscow "Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department"
State Budgetary Healthcare Institution "Moscow Clinical Scientific and Practical Center of the Department of Public Health of Moscow"
State Budgetary Educational Institution of Higher Professional Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
Medical Company "Hepatolog"
Stavropol Regional Clinical Hospital
State Budgetary institution of the Republic of Sakha (Yakutia) "Yakutsk Clinical Hospital"

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm C

Arm D

Arm Description

Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

tenofovir treatment for 48 weeks

Outcomes

Primary Outcome Measures

HDV RNA Response at Week 24

HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24

Secondary Outcome Measures

Durability of HDV RNA Response

Durability of HDV RNA response to 24 weeks post treatment

Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24

Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24

Changes in ALT Values

Changes in ALT values at Week 24 and Week 48 compared to baseline.

Change (Absence of Increase) in Fibrosis Marker

Change (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline

Change in Hepatitis B Surface Antigen

Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels, disappearance of HBsAg and HBsAg seroconversion to anti-HBsAg) at week 24 and week 48 compared to baseline

Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline

Change in hepatitis B virus (HBV) DNA levels at Week 24 and Week 48 compared to baseline.

Absence of a Fibrosis Progression According to the Findings of Transient Elastometry

Decrease in liver stiffness and absence of a fibrosis progression according to the findings of transient elastometry (fibroscan) at week 24 compared to baseline

Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results

Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results at week 24 compared to baseline. 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.

Full Information

NCT ID

NCT03546621

First Posted

May 23, 2018

Last Updated

April 13, 2021

Sponsor

Hepatera Ltd.

Collaborators

Data Matrix Solutions

1. Study Identification

Unique Protocol Identification Number

NCT03546621

Brief Title

A Multicenter, Open-label, Randomized Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination With Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients With Chronic Hepatitis D

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

February 16, 2016 (Actual)

Primary Completion Date

January 31, 2018 (Actual)

Study Completion Date

January 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hepatera Ltd.

Collaborators

Data Matrix Solutions

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a multicenter, open-label, randomized clinical trial to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination with Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients with Chronic Hepatitis D

Detailed Description

This is a multicenter, open-label, randomised, phase II study. The study will be conducted in Russia and Germany. The study is designed to evaluate the benefit of 3 MXB doses versus observation in patients on background therapy with tenofovir, suffering from hepatitis delta with very limited therapeutic options; the patients will be randomized 1:1:1:1 into 3 treatment arms and an observation arm. Patients with compensated cirrhosis at screening will be stratified to allow similar distribution into each treatment arm. If patients were not receiving treatment with nucleoside/nucelotide analogue, the comparator/background drug will be initiated after the eligibility confirmation, for 12 weeks prior to randomization visit; patients who previously received tenofovir will continue the dosing; patients on different nucleoside/nucleotide analogue will be switched to tenofovir. Observation is considered an adequate control group, as daily placebo injections for 24 weeks are regarded not feasible and ethically questionable. It is planned to screen 200 patients, and 120 patients will be randomised into four treatment arms in the 1:1:1:1 ratio. Arm A (30 patients): Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Arm B (30 patients): Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Arm C (30 patients): Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Arm D (30 patients): tenofovir treatment for 48 weeks.

6. Conditions and Keywords

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

Chronic Hepatitis D Infection With Hepatitis B

Keywords

Hepatitis D

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Multicenter, Open-label, Randomized

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

Arm Title

Arm B

Arm Type

Experimental

Arm Description

Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

Arm Title

Arm C

Arm Type

Experimental

Arm Description

Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

Arm Title

Arm D

Arm Type

Active Comparator

Arm Description

tenofovir treatment for 48 weeks

Intervention Type

Drug

Intervention Name(s)

Myrcludex B

Intervention Description

2 mg, once daily, subcutaneously

Intervention Type

Drug

Intervention Name(s)

Myrcludex-B

Intervention Description

5 mg, once daily, subcutaneously

Intervention Type

Drug

Intervention Name(s)

Myrcludex-B

Intervention Description

10 mg, once daily, subcutaneously

Intervention Type

Drug

Intervention Name(s)

Tenofovir

Other Intervention Name(s)

Viread

Intervention Description

tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Primary Outcome Measure Information:

Title

HDV RNA Response at Week 24

Description

HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Durability of HDV RNA Response

Description

Durability of HDV RNA response to 24 weeks post treatment

Time Frame

48 weeks

Title

Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24

Description

Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24

Time Frame

24 weeks

Title

Changes in ALT Values

Description

Changes in ALT values at Week 24 and Week 48 compared to baseline.

Time Frame

24 and 48 weeks

Title

Change (Absence of Increase) in Fibrosis Marker

Description

Change (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline

Time Frame

24 and 48 weeks

Title

Change in Hepatitis B Surface Antigen

Description

Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels, disappearance of HBsAg and HBsAg seroconversion to anti-HBsAg) at week 24 and week 48 compared to baseline

Time Frame

24 and 48 weeks

Title

Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline

Description

Change in hepatitis B virus (HBV) DNA levels at Week 24 and Week 48 compared to baseline.

Time Frame

24 and 48 weeks

Title

Absence of a Fibrosis Progression According to the Findings of Transient Elastometry

Description

Decrease in liver stiffness and absence of a fibrosis progression according to the findings of transient elastometry (fibroscan) at week 24 compared to baseline

Time Frame

24 weeks

Title

Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results

Description

Time Frame

24 weeks

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: Age from 18 to 65 years inclusively at the time of signing Informed Consent Form. Positive serum HBsAg for at least 6 months before Screening. Positive serum anti-HDV antibody for at least 6 months before screening. Positive PCR results for serum HDV RNA at Screening. Patients with liver cirrhosis, irrespective of previous interferon treatment . Patients without liver cirrhosis, who failed prior interferon treatment or for whom, in the opinion of the Investigator, such treatment is currently contraindicated (including history of interferon intolerance) . Alanine aminotransferase level >1 x ULN, but less than 10 x ULN. Previous nucleotide/nucleoside analogue treatment within at least 12 weeks prior to the planned start of study treatment or subject's willingness to take tenofovir for at least 12 weeks prior to the planned start of study treatment. Negative urine pregnancy test for females of childbearing potential. Inclusion criteria for female subjects: Postmenopausal for at least 2 years, or Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or Abstinence from heterosexual intercourse throughout the study, or Willingness to use highly effective contraception throughout the study and for 3 months after the last dose of the study medication. Male and female subjects must agree to use a highly effective contraception throughout the study and for 3 months after the last dose of the study medication. Male subjects must agree not to donate sperm throughout the study and for 3 months after the last dose of the study medication. Exclusion Criteria: Child-Pugh score of B-C or over 6 points. HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative. Creatinine clearance <60 mL/min. Total bilirubin ≥ 2mg/dL. Patients with higher total bilirubin values may be included after the consultation with the Study's Medical Monitor, if such elevation can be clearly attributed to Gilbert's syndrome associated with low-grade hyperbilirubinemia. Any previous or current malignant neoplasms, including hepatic carcinoma.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Heiner Wedemeyer, MD,PhD

Organizational Affiliation

Dept. of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ifi-Institut für interdisziplinäre Medizin an der Asklepios Klinik St. Georg

City

Hamburg

Country

Germany

Facility Name

Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie

City

Hamburg

Country

Germany

Facility Name

Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

City

Hannover

Country

Germany

Facility Name

UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie

City

Heidelberg

Country

Germany

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 Autonomous Healthcare Institution "Republican Clinical Infectious Diseases Hospital named after Prof. A.F. Agafonov "(SAHI RCID)

City

Kazan

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

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

City

Moscow

Country

Russian Federation

Facility Name

State Budget Health Institution of Moscow "Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department"

City

Moscow

Country

Russian Federation

Facility Name

State Budgetary Healthcare Institution "Moscow Clinical Scientific and Practical Center of the Department of Public Health of Moscow"

City

Moscow

Country

Russian Federation

Facility Name

State Budgetary Educational Institution of Higher Professional Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation

City

Novosibirsk

Country

Russian Federation

Facility Name

Medical Company "Hepatolog"

City

Samara

Country

Russian Federation

Facility Name

Stavropol Regional Clinical Hospital

City

Stavropol'

Country

Russian Federation

Facility Name

State Budgetary institution of the Republic of Sakha (Yakutia) "Yakutsk Clinical Hospital"

City

Yakutsk

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36113537

Citation

Wedemeyer H, Schoneweis K, Bogomolov P, Blank A, Voronkova N, Stepanova T, Sagalova O, Chulanov V, Osipenko M, Morozov V, Geyvandova N, Sleptsova S, Bakulin IG, Khaertynova I, Rusanova M, Pathil A, Merle U, Bremer B, Allweiss L, Lempp FA, Port K, Haag M, Schwab M, Zur Wiesch JS, Cornberg M, Haefeli WE, Dandri M, Alexandrov A, Urban S. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial. Lancet Infect Dis. 2023 Jan;23(1):117-129. doi: 10.1016/S1473-3099(22)00318-8. Epub 2022 Sep 13. Erratum In: Lancet Infect Dis. 2022 Oct 28;:

Results Reference

derived

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