Bulevirtide for Hepatitis D

Recruiting at 6 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Steroids, Immunosuppressants, Chemotherapy, others

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 1 week

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called bulevirtide to understand its behavior in the body and its effects on bile acids, with a focus on safety for individuals with liver issues. The trial includes different groups: some with moderate or severe liver impairment and others with normal liver function. It seeks participants who have had stable liver problems for at least six months without expecting significant changes in their condition. Participants will help researchers explore bulevirtide's potential as a treatment for liver-related conditions. As a Phase 1 trial, this research aims to understand how bulevirtide works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop taking my current medications for this trial?

The protocol does not specify if you must stop taking your current medications. However, individuals with hepatic impairment should have been on a stable dose of their medications for at least 4 weeks prior to screening, and any changes in medication should be reviewed and approved by the sponsor. Matched control individuals with normal hepatic function should not have taken any prescription or over-the-counter medications, except for certain exceptions, within 28 days prior to the study.

Is there any evidence suggesting that bulevirtide is likely to be safe for humans?

Research has shown that bulevirtide (BLV) is generally safe and well-tolerated for people with chronic hepatitis D. One study found that after 48 weeks of treatment, patients had lower virus levels and improved liver function. Another study in real-world settings found that taking bulevirtide for up to 96 weeks was safe, with many patients responding positively. In July 2023, bulevirtide received full approval for treating chronic hepatitis D, indicating strong safety evidence. Overall, while some side effects may occur, data shows bulevirtide is safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Hepatitis D, which often involve interferon-based therapies, Bulevirtide offers a new approach by targeting the entry of the Hepatitis D virus into liver cells. Researchers are excited about Bulevirtide because it specifically blocks the NTCP receptor, which the virus uses to enter the cells, potentially reducing viral load more effectively. Additionally, Bulevirtide is administered via injection, allowing for precise dosing and potentially fewer side effects compared to oral medications. This novel mechanism of action and delivery method could provide a more targeted and efficient treatment option for patients with varying degrees of liver impairment.

What evidence suggests that bulevirtide might be an effective treatment for Hepatitis D?

Research has shown that bulevirtide effectively treats hepatitis D. In one study, 90% of patients with long-term hepatitis D who reached undetectable virus levels with bulevirtide maintained those levels even after stopping the treatment. Another study found that after 48 weeks of using bulevirtide, patients had lower virus levels and improved liver enzyme levels. In real-world use, bulevirtide proved safe and effective, with 79% of patients showing a positive response after 96 weeks. This trial will evaluate bulevirtide in different groups based on hepatic impairment, with participants receiving varying dosages. Overall, bulevirtide appears to help control the virus and improve liver health in hepatitis D patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with chronic Hepatitis D, who are healthy enough as per medical evaluation, have a BMI between 19-40 kg/m^2, and kidney function above a certain level. They must agree to use contraception if applicable and not donate blood during the study. People with recent drug treatments or substance abuse issues, significant allergies or serious health conditions cannot participate.

Inclusion Criteria

I have liver issues but meet specific health criteria and have been on stable medication for 4 weeks.

All individuals must have a body mass index (BMI) of at least 19 and no greater than 40 kg/m^2 at screening.

I am generally healthy apart from liver issues, as confirmed by my doctor's exams and tests.

Exclusion Criteria

All individuals must not have current alcohol or substance abuse that could interfere with individual compliance or safety.

I do not have issues with blood draws due to poor vein access.

All individuals must not have received any study drug within 30 days prior to study dosing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Bulevirtide (BLV) injections once daily for 6 days to evaluate pharmacokinetics and safety

1 week

Daily visits for 6 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bulevirtide

Trial Overview The study tests Bulevirtide in people with varying liver functions. It measures how much of the drug enters the bloodstream, its elimination rate, impact on bile acids, and assesses safety over multiple doses.

How Is the Trial Designed?

Group I: Group D: BLV, Severe Hepatic Impairment Experimental Treatment 1 Intervention

Participants from Group B, whose safety and PK data had been reviewed and their matched control group participants with normal hepatic function, will receive BLV 10 mg injection once daily for 6 days.

Group II: Group C: Bulevirtide (BLV), Moderate Hepatic Impairment Experimental Treatment 1 Intervention

Participants from Group A, whose safety and phamacokinetic (PK) data had been reviewed and their matched control group participants with normal hepatic function, will receive BLV 10 mg injection once daily for 6 days.

Group III: Group B: BLV, Severe Hepatic Impairment Experimental Treatment 1 Intervention

Participants with severe hepatic impairment and their matched control group participants with normal hepatic function will receive BLV 2 mg injection once daily for 6 days starting on Day 1.

Group IV: Group A: Bulevirtide (BLV), Moderate Hepatic Impairment Experimental Treatment 1 Intervention

Participants with moderate hepatic impairment and their matched control group participants with normal hepatic function will receive BLV 2 mg injection once daily for 6 days starting on Day 1.

Bulevirtide is already approved in European Union for the following indications:

Approved in European Union as Hepcludex for:

• Chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

Myrcludex B, a new entry inhibitor for hepatitis B and D, was well tolerated in a pilot trial with 24 patients, showing no serious adverse events and significant reductions in HDV RNA levels after 24 weeks of treatment.

The combination of Myrcludex B with pegylated interferon alpha (PegIFNα-2a) demonstrated a strong synergistic effect, leading to negative HDV RNA results in five out of seven patients, indicating enhanced efficacy in treating chronic hepatitis delta virus infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study. Bogomolov, P., Alexandrov, A., Voronkova, N., et al.[2018]

In a compassionate use study of 3 European patients with HDV-related compensated cirrhosis, long-term treatment with Myrcludex-B (MyrB) at 10 mg/day for 48 weeks was found to be safe and effective, leading to undetectable HDV RNA levels in two patients and significant improvements in liver function tests.

MyrB treatment resulted in normalization of alanine aminotransferase levels and improvements in portal hypertension features, demonstrating its potential as a viable therapy for patients with advanced liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients. Loglio, A., Ferenci, P., Uceda Renteria, SC., et al.[2020]

Bulevirtide (Hepcludex®) is the first entry inhibitor approved in the European Union for treating chronic hepatitis delta virus (HDV) infections in adults with compensated liver disease.

The approval of bulevirtide marks a significant milestone in the treatment of chronic HDV and chronic hepatitis B virus (HBV) infections, highlighting its potential as a new therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bulevirtide: First Approval. Kang, C., Syed, YY.[2021]

Myrcludex B, a new treatment for hepatitis B and D, was well tolerated in a phase I clinical trial involving 36 healthy volunteers, with no serious adverse effects observed even at the highest dose of 20mg.

The pharmacokinetics of Myrcludex B followed a 2-compartment model, showing that subcutaneous doses of 10mg and above can achieve over 80% target saturation for at least 15 hours, which is important for planning future efficacy trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. Blank, A., Markert, C., Hohmann, N., et al.[2018]

In a study involving 114 patients with chronic hepatitis D, bulevirtide treatment resulted in a significant virologic response in 76% of cases, with a mean time to response of 23 weeks, demonstrating its efficacy as a monotherapy.

The treatment was well tolerated with no serious drug-related adverse events reported, and improvements in liver inflammation were noted even in patients who did not achieve a virologic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating hepatitis D with bulevirtide - Real-world experience from 114 patients. Dietz-Fricke, C., Tacke, F., Zöllner, C., et al.[2023]

In a real-life study involving seven patients with chronic hepatitis delta, the combination of bulevirtide (BLV) and tenofovir disoproxil fumarate (TDF) showed promising efficacy, with five out of seven patients achieving a significant reduction in HDV RNA after 24 weeks.

The treatment was well-tolerated with no reported adverse effects, confirming the safety and efficacy of BLV as seen in the earlier MYR202 trial, even with extended treatment in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection. Herta, T., Hahn, M., Maier, M., et al.[2023]

Myrcludex B is a novel entry inhibitor that effectively blocks HBV and HDV from entering liver cells by targeting the sodium-taurocholate co-transporting polypeptide, which is the main receptor for these viruses.

This drug not only inhibits HBV replication but also shows potential for further development, as it is being considered for phase III clinical trials, addressing the urgent need for new antiviral treatments for chronic hepatitis B and D infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of NTCP-inhibitor myrcludex B. Cheng, D., Han, B., Zhang, W., et al.[2021]

Bulevirtide (BLV) shows promising early virological efficacy in treating chronic hepatitis delta (CHD), with four out of six patients experiencing significant declines in HDV viral load after 12 and 24 weeks of treatment, especially those receiving combination therapy with pegylated interferon.

The treatment was generally well-tolerated, although one patient experienced thrombocytopenia leading to treatment cessation, highlighting the need for monitoring side effects. Overall, these preliminary results support the potential of BLV as a new therapeutic option for CHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life. Asselah, T., Loureiro, D., Le Gal, F., et al.[2022]

Citations

1. gilead.com gilead.com/news/news-details/2025/final-data-from-the-phase-3-myr301-study-demonstrated-longer-treatment-with-bulevirtide-was-associated-with-sustaining-undetectability-after-stopping-treatment

Final Data From the Phase 3 MYR301 Study Demonstrated ... 90% of adults with chronic hepatitis delta virus (HDV) who achieved undetectable HDV RNA at 96 weeks of treatment with bulevirtide remained undetectable for ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213429

A Phase 3, Randomized Trial of Bulevirtide in Chronic ... After 48 weeks of bulevirtide treatment, HDV RNA and ALT levels were reduced in patients with chronic hepatitis D.

3. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(24)00333-7/fulltext

Bulevirtide monotherapy in patients with chronic HDV Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39960163/

Bulevirtide in Chronic Hepatitis D Patients Awaiting Liver ... Twelve patients (60%) underwent LT. No serious adverse events occurred. Bulevirtide improved liver function, enabling one (7.1%) HCC patient to undergo ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168827825000017

Real-world effectiveness and safety of bulevirtide ... Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11907224/

Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic ... The safety and tolerability of bulevirtide (BLV), a novel entry inhibitor of hepatitis delta virus, were evaluated in an integrated analysis of clinical trial ...