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

Karolinska University Hospital400 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

400

Conditions

Chronic Hepatitis D

Interventions

BulevirtideDRUG

Hepcludex, 2 mg daily subcutaneous injection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Karolinska University Hospital, Department of Infectious Diseases

Stockholm, Sweden

RECRUITING

Outcomes

Primary Outcomes

Percentage of patients with virological response of Hepatitis D virus (HDV) RNA < Limit of Detection (LoD) at FU 12 months after End of Treatment (EOT).

Measurement of virological response of HDV RNA \< LoD

Time frame: Continuously, up to 12 months

Secondary Outcomes

Percentage of patients with virological response of HDV RNA < LoD

Percentage of patients with virological response of HDV RNA \< LoD at at month 1, 3 and every 3 months after treatment start, and FU month 3, 6, and 9 after EOT.

Time frame: At Baseline, 1 and 3 months, every 3 months after treatment start up to 9 months after date of EOT.

Percentage of patients with Hepatitis B surface antigen (HBsAg) < LoD

Percentage of patients with HBsAg \< LoD at month 1 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.

Time frame: At Baseline, 1 and 3 months, every 3 months after treatment start up to 12 months after date of EOT.

Change of HBsAg from baseline

Change of HBsAg from baseline every 3 months during study period.

Time frame: From Baseline every 3 months until end of study.

Percentage of patients with HDV RNA < LoD or HDV RNA reduction of at least 2 log10 compared to baseline

Percentage of patients with HDV RNA \< LoD or HDV RNA reduction of at least 2 log10 compared to baseline, at month 1 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.

Time frame: At Baseline, 1 and 3 months, every 3 months after treatment start up to 12 months after date of EOT.

Percentage of patients with virological relapse, defined as HDV RNA < LoD at EOT and increase of HDV RNA to > LoD after EOT

Central Contacts

Soo Aleman, MD, PhD

CONTACT

+46 72-595 72 25 soo.aleman@regionstockholm.se

Data from ClinicalTrials.gov

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