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

NCT03546621 | Completed Phase 2 Results

• 1 other identifier: MYR 202
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 15

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

Conditions

Chronic Hepatitis D Infection With Hepatitis B

Keywords

Hepatitis D

Outcome Measures

Primary Outcomes (1)

• HDV RNA Response at Week 24

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

  24 weeks

Secondary Outcomes (8)

• Durability of HDV RNA Response

  48 weeks

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

  24 weeks

• Changes in ALT Values

  24 and 48 weeks

• Change (Absence of Increase) in Fibrosis Marker

  24 and 48 weeks

• Change in Hepatitis B Surface Antigen

  24 and 48 weeks

Study Arms (4)

Arm A

EXPERIMENTAL

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.

Drug: Myrcludex B; Drug: Tenofovir

Arm B

EXPERIMENTAL

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.

Drug: Myrcludex-B; Drug: Tenofovir

Arm C

EXPERIMENTAL

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.

Drug: Myrcludex-B; Drug: Tenofovir

Arm D

ACTIVE COMPARATOR

tenofovir treatment for 48 weeks

Drug: Tenofovir

Interventions

Myrcludex B DRUG

2 mg, once daily, subcutaneously

Arm A

Myrcludex-B DRUG

5 mg, once daily, subcutaneously

Arm B

Tenofovir DRUG

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

Also known as: Viread

Arm A; Arm B; Arm C; Arm D

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hepatera Ltd.: lead
• Data Matrix Solutions: collaborator

Study Sites (15)

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

Hamburg, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie

Hamburg, Germany

Location

Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

Hanover, Germany

Location

UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie

Heidelberg, Germany

Location

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

Chelyabinsk, Russia

Location

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

Kazan', Russia

Location

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

Location

LLC "Clinic of Modern Medicine"

Moscow, Russia

Location

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

Moscow, Russia

Location

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

Moscow, Russia

Location

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

Moscow, Russia

Location

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

Novosibirsk, Russia

Location

Medical Company "Hepatolog"

Samara, Russia

Location

Stavropol Regional Clinical Hospital

Stavropol, Russia

Location

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

Yakutsk, Russia

Location

Related Publications (3)

• 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.

  PMID: 38340811 DERIVED

• 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.

  PMID: 37120031 DERIVED

• 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.

  PMID: 36113537 DERIVED

MeSH Terms

Conditions

Hepatitis D

Interventions

myrcludex-B; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr.Alexander Alexandrov
• Organization: Hepatera LLC

alexandrov@myr-pharma.com

+7 (495) 726-52-53

Study Officials

• Heiner Wedemeyer, MD,PhD

  Dept. of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, Open-label, Randomized

Study Record Dates

• First Submitted: May 23, 2018
• First Posted: June 6, 2018
• Study Start: February 16, 2016
• Primary Completion: January 31, 2018
• Study Completion: January 31, 2018
• Last Updated: May 10, 2021
• Results First Posted: December 30, 2019

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); RU (11)