Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Chronic Hepatitis D Patients

Observational Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Patients With Chronic Hepatitis D

The aim is to assess the efficacy and specific safety in an observational study of patients with Chronic hepatitis D (CHD) with prospective follow-up, with antiviral treatment of 2 mg Bulevirtide (BLV) +/- PEG-IFNα-2a and +/- NA given as part of the patient's routine medical care. Also, explorative endpoints of biomarkers in peripheral blood, saliva, fecal sample and/or intrahepatic markers/signatures, and quality of life outcomes will be assessed.

Chronic hepatitis D (CHD) is considered to be the most severe form of hepatitis. It is a rare disease in European Union countries, with status of an orphan disease. Historically, only pegylated interferon alfa-2a (PEG-IFNα-2a) +/- nucleos(t)ide analogues (NA) have been used off-label for treatment of CHD, with insufficient virological response and frequent relapse. The first in class entry inhibitor for treatment of CHD, bulevirtide (BLV), product name Hepcludex) has received status of conditional marketing authorization by the European Medical Agency (EMA) in July 2020.

This conditional approval was based on two phase 2 studies, with limited sample sizes. A phase 3 clinical trial of 150 participants is ongoing.

Besides need of more efficacy and safety data, knowledge about immunological cellular response in BLV treated and identification of biomarkers for treatment response is needed. Observational studies with biological samplings are thus needed.

We aimed therefore to assess the efficacy and specific safety in an observational study with prospective follow-up, with antiviral treatment of 2 mg BLV +/- PEG-IFNα-2a and +/- NA given as part of the patient's routine medical care. Also, explorative endpoints of biomarkers in peripheral blood, saliva, fecal sample and/or intrahepatic markers/signatures, and quality of life outcomes will be assessed.

Inclusion Criteria:

1. Age > 18 years

2. Diagnosis of chronic HBV/HDV co-infection.

3. Have compensated liver disease (presence of portal hypertension without ongoing hepatic decompensation as ascites, variceal bleeding and hepatic encephalopathy allowed).

4. Have indication for treatment of BLV, or already treated with BLV.

5. For female* participants:

   1. Postmenopausal for at least one year, or
   2. Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or
   3. Abstinence from heterosexual intercourse throughout the treatment period, or
   4. Willingness to use highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive) throughout the treatment period and for 6 months after last dose of the drugs in the study.

6. Male participants must agree to use a highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive used by female partners) throughout the treatment period and for 6 months after last dose of the drugs in the study.

7. Participants who are willing to give written informed consent

Exclusion Criteria:

1. Any contra-indications to treatment with BLV, including any intolerance or hypersensitivity to the active ingredient or other components of BLV.
2. Pregnant or breast-feeding women.
3. Patients with predictable difficulties of follow-up according to the investigator.
4. Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study.