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

NCT ID: NCT03546621

Last Updated: 2021-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-16
• Study Completion Date: 2018-01-31

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.

Conditions

Chronic Hepatitis D Infection With Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

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.

Group Type: EXPERIMENTAL

Myrcludex B

Intervention Type: DRUG

2 mg, once daily, subcutaneously

Tenofovir

Intervention Type: DRUG

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

Arm B

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.

Group Type: EXPERIMENTAL

Myrcludex-B

Intervention Type: DRUG

5 mg, once daily, subcutaneously

Tenofovir

Intervention Type: DRUG

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

Arm C

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.

Group Type: EXPERIMENTAL

Myrcludex-B

Intervention Type: DRUG

10 mg, once daily, subcutaneously

Tenofovir

Intervention Type: DRUG

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

Arm D

tenofovir treatment for 48 weeks

Group Type: ACTIVE_COMPARATOR

Tenofovir

Intervention Type: DRUG

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

Interventions

Myrcludex B

2 mg, once daily, subcutaneously

Intervention Type: DRUG

Myrcludex-B

5 mg, once daily, subcutaneously

Intervention Type: DRUG

Myrcludex-B

10 mg, once daily, subcutaneously

Intervention Type: DRUG

Tenofovir

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

Intervention Type: DRUG

Other Intervention Names

Viread

Eligibility Criteria

Inclusion Criteria

1. Age from 18 to 65 years inclusively at the time of signing Informed Consent Form.

2. Positive serum HBsAg for at least 6 months before Screening.

3. Positive serum anti-HDV antibody for at least 6 months before screening.

4. Positive PCR results for serum HDV RNA at Screening.

5. Patients with liver cirrhosis, irrespective of previous interferon treatment .

6. 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) .

7. Alanine aminotransferase level >1 x ULN, but less than 10 x ULN.

8. 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.

9. Negative urine pregnancy test for females of childbearing potential.

• 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.

11. 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.

12. 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

1. Child-Pugh score of B-C or over 6 points.

2. HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative.

3. Creatinine clearance <60 mL/min.

4. 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.

5. Any previous or current malignant neoplasms, including hepatic carcinoma.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Data Matrix Solutions

OTHER

Sponsor Role: collaborator

Hepatera Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heiner Wedemeyer, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover

Locations

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

Hamburg, , Germany

Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie

Hamburg, , Germany

Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

Hanover, , Germany

UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie

Heidelberg, , Germany

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

Chelyabinsk, , Russia

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

Kazan', , Russia

Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance

Moscow, , Russia

LLC "Clinic of Modern Medicine"

Moscow, , Russia

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

Moscow, , Russia

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

Moscow, , Russia

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

Moscow, , Russia

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

Novosibirsk, , Russia

Medical Company "Hepatolog"

Samara, , Russia

Stavropol Regional Clinical Hospital

Stavropol, , Russia

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

Yakutsk, , Russia

Countries

Germany; Russia

References

Allweiss L, Volmari A, Suri V, Wallin JJ, Flaherty JF, Manuilov D, Downie B, Lutgehetmann M, Bockmann JH, Urban S, Wedemeyer H, Dandri M. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies. J Hepatol. 2024 Jun;80(6):882-891. doi: 10.1016/j.jhep.2024.01.035. Epub 2024 Feb 8.

Reference Type: DERIVED

PMID: 38340811 (View on PubMed)

Hollnberger J, Liu Y, Xu S, Chang S, Martin R, Manhas S, Aeschbacher T, Han B, Yazdi T, May L, Han D, Shornikov A, Flaherty J, Manuilov D, Suri V, Asselah T, Lampertico P, Wedemeyer H, Aleman S, Richards C, Mateo R, Maiorova E, Cihlar T, Mo H, Urban S. No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta. J Hepatol. 2023 Sep;79(3):657-665. doi: 10.1016/j.jhep.2023.04.027. Epub 2023 Apr 27.

Reference Type: DERIVED

PMID: 37120031 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36113537 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form: Protocol_v.7.0_28.09.2017_Russia + SAP + ICF

View Document

Document Type: Study Protocol: Protocol_v.3.0_25.12.2107_Germany

View Document

Other Identifiers

MYR 202

Identifier Type: -

Identifier Source: org_study_id