BuleDelta: Observatory of Efficacy and Safety of Bulevirtide in Patients With Chronic HBV/HDV Co-infection

Sponsor

ANRS, Emerging Infectious Diseases (Other)

Overall Status

Recruiting

CT.gov ID

NCT04166266

Collaborator

(none)

400

Enrollment

Location

80.4

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, multicentric, non comparative study, with a retrospective data collection aiming at evaluating the efficacy and safety of bulevirtide in patients with chronic HBV/HDV co-infection with severe fibrosis injuries, or moderate fibrosis injuries associated with persistent increase of ALT.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis D, Chronic Hepatitis B, Chronic

Detailed Description

Chronic hepatitis delta represents the most severe form of chronic viral hepatitis.The current treatment of hepatitis delta virus (HDV) infection consists in the use of interferon and is largely unsatisfactory. Bulevirtide is an entry inhibitor which has demonstrated significant virologic and biochemical activity in patients with HDV infection in clinical trials.

The ANRS HDEP01 BuleDelta study is an observational cohort, embedded in the french bulevirtide ATU program.

After their inclusion, patients will be followed according to the ATU protocol during treatment within the cohort ATU and according to the usual recommendations during treatment within the nominative ATU (if needed) and after the end of bulevirtide treatment. The patients included will be followed during 48 weeks after the end of their treatment.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Observatory of Efficacy and Safety of Bulevirtide in Patients With Chronic Hepatitis B Virus (HBV)/Hepatitis D Virus (HDV) Co-infection With Severe Fibrosis Injuries, or Moderate Fibrosis Injuries Associated With Persistent Increase of ALT

Actual Study Start Date :

Feb 19, 2020

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

Nov 1, 2026

Outcome Measures

Primary Outcome Measures

Percentage of patients achieving a therapeutic response to bulevirtide [After 48 weeks of treatment]
The therapeutic response is defined as a reduction of RNA HDV of at least 2 log10 and ALT normalization (composite criteria).

Secondary Outcome Measures

HDV RNA level [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of partial virological response [At weeks 4, 8, 12 and every 12 weeks during treatment]
Rate of sustained virological response [24 weeks after the end of treatment]
Rate of sustained virological response [48 weeks after the end of treatment]
Breakthrough rate [At weeks 8, 12 and every 12 weeks during treatment]
Number of different HDV resistance variants [Through treatment period, max 3 years]
Number of patients with at least one resistance variant [Through treatment period, max 3 years]
Rate of biochemical response [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Biochemical response is defined as ALT and aspartate aminotransferase (AST) normalization
Fibrosis level [Every 48 weeks during treatment and week 48 after the end of treatment]
Rate of patients achieving HBV DNA indetectability [Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of patients achieving hepatitis B e (HBe) Ag negativation in patient initially HBeAg- positive [Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of patients with appearance of anti-HBe Ab [Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of patients achieving HBe seroconversion [Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of patients achieving HBs Ag negativation [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of patients with appearance of anti-HBs Ab [At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of patients achieving HBs seroconversion [At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Decrease of HBs Ag from baseline [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of early discontinuation of treatment due to an adverse event [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Rate of adverse event [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Death rate [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Number and characterization of associated treatments [At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment]
Quality of life level measured with short-form 12 (SF12) questionnaire [weeks 24, 48, end of treatment and 48 weeks after the end of treatment]
Number of patient's reported outcomes measured with specific questionnaire [weeks 24, 48, end of treatment and 48 weeks after the end of treatment]
Quality of observance measured with specific questionnaire [weeks 24, 48, end of treatment and 48 weeks after the end of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years,
Presenting a chronic HDV infection,
With an indication for or already treated by bulevirtide within the French compassionate program (ATU)

with compensated cirrhosis or severe liver fibrosis (Metavir fibrosis score 3 or 4 according to liver biopsy or Fibroscan®) or
moderate liver fibrosis (Metavir fibrosis score 2 according to liver biopsy or Fibroscan®) associated with persistent increase of the ALT level (ALT>2*normal for more than 6 months).

Who gave his written informed consent before any intervention and the day of inclusion at the latest,
Affiliated to Health Insurance or to the "Aide Médicale d'Etat" (request for exemption pending).

Exclusion Criteria:

Contra-indications to treatment with bulevirtide : hypersensibility to the substance or to one of its excipients ,
Patient participating in another biomedical research with an exclusion period ongoing at inclusion,
Vulnerable patient (minor, pregnant or breastfeeding woman, adults legally protected: under judicial protection, guardianship, or supervision, persons deprived of their liberty).
Patients with predictable difficulties of follow-up according to the investigator.