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

August 18, 2023 updated by: ANRS, Emerging Infectious Diseases

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

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.

Study Overview

Status

Recruiting

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 Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Angers, France
        • Recruiting
        • CHU of Angers
        • Principal Investigator:
          • Isabelle FOUCHARD
      • Clichy, France
        • Recruiting
        • Beaujon hospital
        • Principal Investigator:
          • Tarik Asselah
      • Lyon, France
        • Recruiting
        • Hopital de la Croix Rousse
        • Principal Investigator:
          • Fabien Zoulim
      • Lyon, France
        • Recruiting
        • Croix Rousse Hospital
        • Principal Investigator:
          • Dulce ALFAIATE
      • Nantes, France
        • Recruiting
        • Hôtel-Dieu Hospital
        • Principal Investigator:
          • François RAFFI
      • Paris, France
        • Recruiting
        • Hopital Tenon
        • Principal Investigator:
          • Julie CHAS
      • Paris, France
        • Recruiting
        • Pitié-Salpêtrière Hospital
        • Principal Investigator:
          • Marc-Antoine VALANTIN
      • Paris, France
        • Recruiting
        • Bichat-Claude Bernard Hospital
        • Principal Investigator:
          • Anne GERVAIS
      • Paris, France
        • Recruiting
        • Saint Louis Hospital
        • Principal Investigator:
          • Caroline Lascoux-Combe
      • Paris, France
        • Recruiting
        • Saint-Antoine Hospital
        • Principal Investigator:
          • Karine Lacombe
      • Toulouse, France
        • Recruiting
        • Hopital Rangueil
        • Principal Investigator:
          • Laurent Alric

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All patients followed in the participating centers for their HBV/HDV co-infection and treated or with an indication for treatment with bulevirtide within the french compassionate use program (ATU nominative ou de cohorte) are susceptible to be included.

Patients who already started their treatment will be included retrospectively, after they have signed an informed consent.

Description

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)

    1. with compensated cirrhosis or severe liver fibrosis (Metavir fibrosis score 3 or 4 according to liver biopsy or Fibroscan®) or
    2. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients achieving a therapeutic response to bulevirtide
Time Frame: 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).
After 48 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HDV RNA level
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment
At weeks 4, 8, 12 and every 12 weeks during treatment
Rate of sustained virological response
Time Frame: 24 weeks after the end of treatment
24 weeks after the end of treatment
Rate of sustained virological response
Time Frame: 48 weeks after the end of treatment
48 weeks after the end of treatment
Breakthrough rate
Time Frame: At weeks 8, 12 and every 12 weeks during treatment
At weeks 8, 12 and every 12 weeks during treatment
Number of different HDV resistance variants
Time Frame: Through treatment period, max 3 years
Through treatment period, max 3 years
Number of patients with at least one resistance variant
Time Frame: Through treatment period, max 3 years
Through treatment period, max 3 years
Rate of biochemical response
Time Frame: 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
At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Fibrosis level
Time Frame: Every 48 weeks during treatment and week 48 after the end of treatment
Every 48 weeks during treatment and week 48 after the end of treatment
Rate of patients achieving HBV DNA indetectability
Time Frame: Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Rate of patients achieving HBe seroconversion
Time Frame: Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Rate of patients achieving HBs Ag negativation
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment
At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment
Rate of patients achieving HBs seroconversion
Time Frame: At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment
At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment
Decrease of HBs Ag from baseline
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: At weeks 4, 8, 12 and every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
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
Time Frame: weeks 24, 48, end of treatment and 48 weeks after the end of treatment
weeks 24, 48, end of treatment and 48 weeks after the end of treatment
Number of patient's reported outcomes measured with specific questionnaire
Time Frame: weeks 24, 48, end of treatment and 48 weeks after the end of treatment
weeks 24, 48, end of treatment and 48 weeks after the end of treatment
Quality of observance measured with specific questionnaire
Time Frame: weeks 24, 48, end of treatment and 48 weeks after the end of treatment
weeks 24, 48, end of treatment and 48 weeks after the end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Fabien ZOULIM, Hôpital de la Croix-Rousse
  • Principal Investigator: Victor DE LEDINGHEN, Hôpital Haut-Lévêque

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 19, 2020

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

September 12, 2019

First Submitted That Met QC Criteria

November 15, 2019

First Posted (Actual)

November 18, 2019

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 18, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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