Bulevirtide for Hepatitis D

No longer recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: MYR GmbH

Must not be taking: Psychotropic agents, Interferons

Disqualifiers: Hepatitis C, Uncontrolled HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 96-144 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, bulevirtide, for individuals with chronic hepatitis delta, a serious liver infection. Participants will receive either 2 mg or 10 mg of bulevirtide daily through a small injection under the skin and will be compared to those who begin treatment later. The study will last up to 240 weeks, with the first 48 weeks focusing on the initial treatment phase. Eligible participants must have tested positive for the hepatitis delta virus for at least six months and have elevated liver enzyme levels. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that individuals receiving certain prohibited treatments at screening cannot join the study unless they stop those treatments before randomization.

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

Previous studies have shown that bulevirtide is safe and well-tolerated in people with chronic hepatitis D. Research indicates that patients taking bulevirtide for up to 96 weeks did not encounter major safety issues. As the first approved treatment for hepatitis D in Europe, its safety is further supported. While some side effects were reported, they were generally manageable. For most people, current evidence considers bulevirtide safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hepatitis D?

Researchers are excited about bulevirtide for hepatitis D because it offers a unique approach compared to existing treatments, which primarily include interferon-based therapies. Bulevirtide works by blocking the entry of the hepatitis D virus into liver cells, which is different from the typical immune-boosting action of interferons. This mechanism not only targets the virus directly but also has the potential to be more effective with fewer side effects. Additionally, bulevirtide is administered subcutaneously, offering a more convenient and potentially more tolerable option for patients.

What evidence suggests that bulevirtide might be an effective treatment for chronic hepatitis delta?

This trial will evaluate different dosing regimens of bulevirtide for treating chronic hepatitis delta (CHD). Studies have shown that bulevirtide is effective for CHD. In one study, 90% of adults who took bulevirtide for 96 weeks had no detectable hepatitis delta virus in their blood, and this remained the case even after they stopped the treatment. Another study found that 95% of patients completed the 96-week treatment, with their health either improving or staying the same. Additionally, research has shown that taking 2 mg of bulevirtide daily is safe and effective, with 79% of patients experiencing a significant drop in virus levels in their blood after 96 weeks. These findings suggest that bulevirtide could be a promising option for managing CHD. Participants in this trial will receive either 2 mg or 10 mg of bulevirtide daily, or they will begin with a delayed treatment of 10 mg/day after an observational period. ^{1 3 6 7 8}

Who Is on the Research Team?

Gilead Medical Monitor

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for adults with chronic hepatitis delta (CHD) who have detectable HDV RNA, moderately elevated liver enzymes, and normal serum albumin levels. Women must not be pregnant and should use effective contraception or be postmenopausal/surgically sterile. Participants cannot join if they have severe kidney issues, certain heart conditions, uncontrolled hypertension, mental disorders affecting protocol adherence, recent serious liver disease events, low blood counts, recent interferon treatment or organ transplants.

Inclusion Criteria

Individuals must agree to use a highly effective contraception and not to donate sperm throughout the study and for 3 months after the last dose of the study medication for participants discontinued during the treatment period

Provision of signed and dated informed consent form

Positive PCR results for serum/plasma HDV RNA at screening

Exclusion Criteria

I haven't used interferons in the last 6 months.

White blood cells (WBC) count < 3000 cells/mm^3 (<1500 if African participants)

Neutrophil count < 1500 cells/mm^3 (<1000 if African participants)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational Period

Participants in the delayed treatment group undergo an observational period before starting treatment

48 weeks

Treatment

Participants receive bulevirtide treatment, either 2 mg/day or 10 mg/day, subcutaneously

96-144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

96 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bulevirtide

Trial Overview The study tests the effectiveness of bulevirtide in treating CHD compared to a delayed treatment approach. It aims to see how well bulevirtide works over time by monitoring participants' health status before starting them on the drug.

How Is the Trial Designed?

Group I: Delayed Treatment/Bulevirtide 10 mg/day Experimental Treatment 1 Intervention

After an observational period of 48 weeks, participants will receive treatment with bulevirtide 10 mg/day subcutaneously (SC) for 96 weeks and will be followed for up to 96 weeks (Up to Week 240).

Group II: Bulevirtide 2 mg/day Experimental Treatment 1 Intervention

Participants will receive bulevirtide 2 mg/day SC for 144 weeks and will be followed for up to 96 weeks (Up to Week 240).

Group III: Bulevirtide 10 mg/day Experimental Treatment 1 Intervention

Participants will receive bulevirtide 10 mg/day SC for 144 weeks and will be followed for up to 96 weeks (Up to Week 240).

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?

MYR GmbH

Lead Sponsor

Trials

2

Recruited

330+

MYR GmbH

Lead Sponsor

Trials

2

Recruited

330+

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

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]

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]

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]

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]

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]

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]

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, 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]

Citations

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

A Phase 3, Randomized Trial of Bulevirtide in Chronic ... A phase 2 trial is evaluating the efficacy of bulevirtide administered with pegylated interferon alfa, as compared with bulevirtide alone and pegylated ...

2. 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38734383/

Bulevirtide monotherapy in patients with chronic HDV Results: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, ...

4. 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

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. gilead.com gilead.com/news/news-details/2023/hepcludex-bulevirtide-demonstrates-sustained-efficacy-and-safety-profile-in-people-with-chronic-hepatitis-delta-virus-at-96-weeks

Hepcludex Bulevirtide Demonstrates Sustained Efficacy ... The 96 Week data not only reinforces the efficacy and safety of bulevirtide as the first and only approved treatment in the EU for people living ...

7. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/hepcludex

Hepcludex | European Medicines Agency (EMA) Hepcludex is an antiviral medicine used to treat chronic (long-term) hepatitis delta virus (HDV) infection in adults and children from 3 years of age and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03852719

Study to Assess Efficacy and Safety of Bulevirtide in ... Efficacy and Safety at 96 weeks of Bulevirtide 2 mg or 10 mg Monotherapy for Chronic Hepatitis D: Results From an Interim Analysis of a Phase 3 Randomized Study ...