Clinical trial NCT03546621: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis D Infection With Hepatitis B
Keywords: Hepatitis D
Lead sponsor: Hepatera Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Data Matrix Solutions
First posted: 2018-06-06
Enrollment: 120
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
Primary purpose: TREATMENT

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.

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.
10. 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.
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.

Primary outcomes:
measure: HDV RNA Response at Week 24
timeFrame: 24 weeks
Secondary outcomes:
measure: Durability of HDV RNA Response
timeFrame: 48 weeks
measure: Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24
timeFrame: 24 weeks
measure: Changes in ALT Values
timeFrame: 24 and 48 weeks
measure: Change (Absence of Increase) in Fibrosis Marker
timeFrame: 24 and 48 weeks
measure: Change in Hepatitis B Surface Antigen
timeFrame: 24 and 48 weeks
measure: Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline
timeFrame: 24 and 48 weeks
measure: Absence of a Fibrosis Progression According to the Findings of Transient Elastometry
timeFrame: 24 weeks
measure: Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: Ifi-Institut für interdisziplinäre Medizin an der Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie
city: Hannover
country: Germany
facility: Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie
city: Chelyabinsk
country: Russian Federation
facility: State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare
city: Kazan
country: Russian Federation
facility: State Autonomous Healthcare Institution "Republican Clinical Infectious Diseases Hospital named after Prof. A.F. Agafonov "(SAHI RCID)
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: Moscow
country: Russian Federation
facility: Moscow Regional Research Clinical Institute n.a. M.F. Vladimirskiy
city: Moscow
country: Russian Federation
facility: State Budget Health Institution of Moscow "Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department"
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution "Moscow Clinical Scientific and Practical Center of the Department of Public Health of Moscow"
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
city: Samara
country: Russian Federation
facility: Medical Company "Hepatolog"
city: Stavropol'
country: Russian Federation
facility: Stavropol Regional Clinical Hospital
city: Yakutsk
country: Russian Federation
facility: State Budgetary institution of the Republic of Sakha (Yakutia) "Yakutsk Clinical Hospital"
Study officials:
affiliation: Dept. of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover
name: Heiner Wedemeyer, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.