Chronic Hepatitis DSEE-DNCT06051045
Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Chronic Hepatitis D Patients
An observational study of Chronic Hepatitis D, run by Karolinska University Hospital at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis D
- What is being tested?
- Bulevirtide
- Type of treatment
- Injection or infusion
- How many people
- 400 participants
- Where
- 1 siteSweden
- Study dates
- 27 Sep 2023to Mar 2033
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Males and females from the age of 18 diagnosed with chronic hepatitis D
Who may be able to join
- Age > 18 years
- Diagnosis of chronic HBV/HDV co-infection.
- Have compensated liver disease (presence of portal hypertension without ongoing hepatic decompensation as ascites, variceal bleeding and hepatic encephalopathy allowed).
- Have indication for treatment of BLV, or already treated with BLV.
- For female* participants:
- Postmenopausal for at least one year, or
Show all 11Show fewer
- Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or
- Abstinence from heterosexual intercourse throughout the treatment period, or
- 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.
- 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.
- Participants who are willing to give written informed consent
Who cannot join
- Any contra-indications to treatment with BLV, including any intolerance or hypersensitivity to the active ingredient or other components of BLV.
- Pregnant or breast-feeding women.
- Patients with predictable difficulties of follow-up according to the investigator.
- Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University Hospital, Department of Infectious Diseases
Stockholm
Soo Aleman, MD, PhD, +46725957225, soo.aleman@regionstockholm.se
Soo Aleman, MD, PhD
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Hepatitis D
- Being tested
- Bulevirtide
- Medical subject headings
- Hepatitis D, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BulevirtideDrug
Hepcludex, 2 mg daily subcutaneous injection
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Continuously, up to 12 months
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: At 0, 3, 6, 9 and 12 months after date of EOT.
Percentage of patients with appearance of hepatitis B surface antibody (anti-HBs)
Percentage of patients with appearance of hepatitis B surface antibody (anti-HBs) at EOT, and FU month 3, 6, 9 and 12 after EOT.
Measured: At 0, 3, 6, 9 and 12 months after date of EOT.
Percentage of patients with HBV DNA level < LoD
Percentage of patients with HBV DNA level < LoD every 3 months during study period.
Measured: From Baseline every 3 months until end of study.
Percentage of patients with biochemical response, defined as normalization of alanine transaminase (ALT)
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.
Measured: At Baseline, 1 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 Alanine Aminotransferase (ALT) normalization
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.
Measured: At Baseline, at 1, 2 and 3 months, every 3 months up to 12 months after date of EOT.
Change of liver elasticity measurement level and percentage of AE of special interest
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.
Measured: At Baseline, every 6 months until 12 months after date of EOT.
Percentage of missed BLV doses during treatment
Percentage of missed BLV doses during treatment.
Measured: Continuously during treatment period until date of EOT.
Percentage of patients with early discontinuation of treatment
Percentage of patients with early discontinuation of treatment and the reasons.
Measured: Continuously during treatment period until date of EOT.
Serious Adverse Events
Percentage of patients with SAE.
Measured: Continuously during study period until end of study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2023
- Study start27 Sep 2023
- Primary completionMar 2033 (estimated)
- Study completionMar 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis DStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Soo Aleman, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06051045
- Sponsor's protocol ID
- SEE-D
- Acronym
- SEE-D
- Status last verified
- Sep 2023
- First submitted
- 6 Sep 2023
- Last updated
- 29 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Patients With Chronic Hepatitis D
- ClinicalTrials.gov ID
- NCT06051045
- Acronym / sponsor ID
- SEE-D / SEE-D
- Conditions
- Chronic Hepatitis D
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Study start
- 27 Sep 2023 (actual)
- Primary completion
- Mar 2033 (estimated)
- Study completion
- Mar 2033 (estimated)
- First posted
- 22 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Males and females from the age of 18 diagnosed with chronic hepatitis D
Key inclusion criteria (11 listed)
- Age > 18 years
- Diagnosis of chronic HBV/HDV co-infection.
- Have compensated liver disease (presence of portal hypertension without ongoing hepatic decompensation as ascites, variceal bleeding and hepatic encephalopathy allowed).
- Have indication for treatment of BLV, or already treated with BLV.
- For female* participants:
Key exclusion criteria (4 listed)
- Any contra-indications to treatment with BLV, including any intolerance or hypersensitivity to the active ingredient or other components of BLV.
- Pregnant or breast-feeding women.
- Patients with predictable difficulties of follow-up according to the investigator.
- Any other condition that, in the opinion of Investigator, precludes the patient from taking part in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BulevirtideHepcludex, 2 mg daily subcutaneous injection | Drug | – |
Primary outcome
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
13 secondary outcomes
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 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.
Change of HBsAg from baseline
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
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
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)
Time frame: At 0, 3, 6, 9 and 12 months after date of EOT.
Percentage of patients with HBV DNA level < LoD
Time frame: From Baseline every 3 months until end of study.
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 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.
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.
Percentage of missed BLV doses during treatment
Time frame: Continuously during treatment period until date of EOT.
Percentage of patients with early discontinuation of treatment
Time frame: Continuously during treatment period until date of EOT.
Serious Adverse Events
Time frame: Continuously during study period until end of study.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Hepatitis D, run by Karolinska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Soo Aleman, MD, PhD (+46 72-595 72 25, soo.aleman@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2023.