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

Chronic Hepatitis D Infection With Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03546621
• Other study ID #: MYR 202
• Status: Completed
• Phase: Phase 2
• Start date: February 16, 2016
• Est. completion date: January 31, 2018

Study information

• Verified date: April 2021
• Source: Hepatera Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 31, 2018
• Est. primary completion date: January 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis D Infection With Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis D
• Hepatitis D, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Myrcludex B
2 mg, once daily, subcutaneously
• Myrcludex-B
5 mg, once daily, subcutaneously
• Myrcludex-B
10 mg, once daily, subcutaneously
• Tenofovir
tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Locations

Country	Name	City	State
Germany	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	Hannover
Germany	UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie	Heidelberg
Russian Federation	State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare	Chelyabinsk
Russian Federation	State Autonomous Healthcare Institution "Republican Clinical Infectious Diseases Hospital named after Prof. A.F. Agafonov "(SAHI RCID)	Kazan
Russian Federation	Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance	Moscow
Russian Federation	LLC "Clinic of Modern Medicine"	Moscow
Russian Federation	Moscow Regional Research Clinical Institute n.a. M.F. Vladimirskiy	Moscow
Russian Federation	State Budget Health Institution of Moscow "Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department"	Moscow
Russian Federation	State Budgetary Healthcare Institution "Moscow Clinical Scientific and Practical Center of the Department of Public Health of Moscow"	Moscow
Russian Federation	State Budgetary Educational Institution of Higher Professional Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation	Novosibirsk
Russian Federation	Medical Company "Hepatolog"	Samara
Russian Federation	Stavropol Regional Clinical Hospital	Stavropol'
Russian Federation	State Budgetary institution of the Republic of Sakha (Yakutia) "Yakutsk Clinical Hospital"	Yakutsk

Sponsors (2)

Lead Sponsor	Collaborator
Hepatera Ltd.	Data Matrix Solutions

Countries where clinical trial is conducted

Germany,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HDV RNA Response at Week 24	HDV RNA negativation or decrease by =2 log10 from baseline to Week 24	24 weeks
Secondary	Durability of HDV RNA Response	Durability of HDV RNA response to 24 weeks post treatment	48 weeks
Secondary	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	24 weeks
Secondary	Changes in ALT Values	Changes in ALT values at Week 24 and Week 48 compared to baseline.	24 and 48 weeks
Secondary	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	24 and 48 weeks
Secondary	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	24 and 48 weeks
Secondary	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.	24 and 48 weeks
Secondary	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	24 weeks
Secondary	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.	24 weeks