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

• ClinicalTrials.gov Identifier: NCT06051045
• Recruitment Status: Recruiting
• First Posted: September 22, 2023
• Last Update Posted: September 29, 2023
• Sponsor: Karolinska University Hospital
• Information provided by (Responsible Party): Soo Aleman, Karolinska University Hospital

Tracking Information

• First Submitted Date: September 6, 2023
• First Posted Date: September 22, 2023
• Last Update Posted Date: September 29, 2023
• Actual Study Start Date: September 27, 2023
• Estimated Primary Completion Date: March 2033 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2023)

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). [ Time Frame: Continuously, up to 12 months ]

Measurement of virological response of HDV RNA < LoD

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 18, 2023)

• Percentage of patients with virological response of HDV RNA < LoD [ 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 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.
• Percentage of patients with Hepatitis B surface antigen (HBsAg) < LoD [ 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 HBsAg < LoD at month 1 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.
• Change of HBsAg from baseline [ Time Frame: From Baseline every 3 months until end of study. ]
  Change of HBsAg from baseline every 3 months during study period.
• Percentage of patients with HDV RNA < LoD or HDV RNA reduction of at least 2 log10 compared to baseline [ 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 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.
• Percentage of patients with virological relapse, defined as HDV RNA < LoD at EOT and increase of HDV RNA to > LoD after EOT [ Time Frame: At 0, 3, 6, 9 and 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, after EOT, at FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with appearance of hepatitis B surface antibody (anti-HBs) [ Time Frame: At 0, 3, 6, 9 and 12 months after date of EOT. ]
  Percentage of patients with appearance of hepatitis B surface antibody (anti-HBs) at EOT, and FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with HBV DNA level < LoD [ Time Frame: From Baseline every 3 months until end of study. ]
  Percentage of patients with HBV DNA level < LoD every 3 months during study period.
• Percentage of patients with biochemical response, defined as normalization of alanine transaminase (ALT) [ Time Frame: At Baseline, 1 and 3 months, every 3 months up to 12 months after date of EOT. ]
  Percentage of patients with biochemical response, defined as normalization of alanine transaminase (ALT), at month 1, 3 and every 3 months during treatment, and FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with combined response, defined as HDV RNA < LoD or HDV RNA reduction of at least 2 log10 compared to baseline and Alanine Aminotransferase (ALT) normalization [ Time Frame: At Baseline, at 1, 2 and 3 months, every 3 months up to 12 months after date of EOT. ]
  Percentage of patients with combined response, defined as HDV RNA < LoD or HDV RNA reduction of at least 2 log10 compared to baseline and ALT normalization, at month 1, 2 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.
• Change of liver elasticity measurement level and percentage of AE of special interest [ Time Frame: At Baseline, every 6 months until 12 months after date of EOT. ]
  Change of liver elasticity measurement level from baseline compared to the level at every 6 months during on-treatment, EOT, and FU month 6 and 12 after EOT. Percentage of AE of special interest: 1. Liver-related event, defined as new diagnoses of liver cirrhosis, HCC, or hepatic decompensation (ascites, variceal bleeding or hepatic encephalopathy); 2. Event of ≥ grade 3 hematological AE (in IFN treated); 3. Event of thyroid disorder (in IFN treated); 4. Event of injection site reaction; 5. Event of≥ grade 3 ALT increase.
• Percentage of missed BLV doses during treatment [ Time Frame: Continuously during treatment period until date of EOT. ]
  Percentage of missed BLV doses during treatment.
• Percentage of patients with early discontinuation of treatment [ Time Frame: Continuously during treatment period until date of EOT. ]
  Percentage of patients with early discontinuation of treatment and the reasons.
• Serious Adverse Events [ Time Frame: Continuously during study period until end of study. ]
  Percentage of patients with SAE.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Chronic Hepatitis D Patients
• Official Title: Observational Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Patients With Chronic Hepatitis D
• Brief Summary: 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.

Detailed Description

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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Biological sampling of blood, saliva and fecal samples and liver tissue (liver biopsy or fine needle aspiration

• Sampling Method: Probability Sample
• Study Population: Males and females from the age of 18 diagnosed with chronic hepatitis D
• Condition: Chronic Hepatitis D

Intervention

Drug: Bulevirtide

Hepcludex, 2 mg daily subcutaneous injection

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 18, 2023): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2033
• Estimated Primary Completion Date: March 2033 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Soo Aleman, MD, PhD; +46 72-595 72 25; soo.aleman@regionstockholm.se

• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT06051045
• Other Study ID Numbers: SEE-D
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Soo Aleman, Karolinska University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Karolinska University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Karolinska University Hospital
• Verification Date: September 2023