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

Hepatitis B, Chronic Clinical Trial

— BuleDelta  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04166266
• Other study ID #: ANRS HD EP01-BULEDELTA
• Status: Recruiting
• Start date: February 19, 2020
• Est. completion date: September 30, 2027

Study information

• Verified date: August 2023
• Source: ANRS, Emerging Infectious Diseases
• Contact: COULIBALY Fatoumata
• Phone: +331 44 23 61 10
• Email: fatoumata.coulibaly[@]anrs.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coinfection
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis D
• Hepatitis D, Chronic

Locations

Country	Name	City	State
France	CHU of Angers	Angers
France	Beaujon Hospital	Clichy
France	Croix Rousse Hospital	Lyon
France	Hôpital de la Croix Rousse	Lyon
France	Hôtel-Dieu Hospital	Nantes
France	Bichat-Claude Bernard Hospital	Paris
France	Hôpital Tenon	Paris
France	Pitié-Salpêtrière Hospital	Paris
France	Saint Louis Hospital	Paris
France	Saint-Antoine Hospital	Paris
France	Hôpital Rangueil	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients achieving a therapeutic response to bulevirtide	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	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
Secondary	Rate of partial virological response		At weeks 4, 8, 12 and every 12 weeks during treatment
Secondary	Rate of sustained virological response		24 weeks after the end of treatment
Secondary	Rate of sustained virological response		48 weeks after the end of treatment
Secondary	Breakthrough rate		At weeks 8, 12 and every 12 weeks during treatment
Secondary	Number of different HDV resistance variants		Through treatment period, max 3 years
Secondary	Number of patients with at least one resistance variant		Through treatment period, max 3 years
Secondary	Rate of biochemical response	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
Secondary	Fibrosis level		Every 48 weeks during treatment and week 48 after the end of treatment
Secondary	Rate of patients achieving HBV DNA indetectability		Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Secondary	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
Secondary	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
Secondary	Rate of patients achieving HBe seroconversion		Every 12 weeks during treatment and weeks 12, 24, 36 and 48 after the end of treatment
Secondary	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
Secondary	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
Secondary	Rate of patients achieving HBs seroconversion		At the end of treatment and weeks 12, 24, 36 and 48 after the end of treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of patient's reported outcomes measured with specific questionnaire		weeks 24, 48, end of treatment and 48 weeks after the end of treatment
Secondary	Quality of observance measured with specific questionnaire		weeks 24, 48, end of treatment and 48 weeks after the end of treatment