Bulevirtide for Hepatitis D

Recruiting at 18 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

150 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug Bulevirtide for treating Hepatitis D?

Bulevirtide has shown promise in treating Hepatitis D by reducing the viral load in patients, as seen in a study where patients experienced a significant decrease in the virus levels after treatment. Additionally, some patients achieved normal liver enzyme levels, indicating improved liver function. ^{1 2 3 4 5}

Is Bulevirtide safe for humans?

Bulevirtide, also known as Hepcludex or Myrcludex-B, has been shown to be safe in humans, with studies reporting it was well tolerated in patients with hepatitis D, even during long-term and high-dose treatments. No significant adverse effects were recorded in real-world studies, confirming its safety and tolerability. ^{1 4 6 7 8}

How is the drug Bulevirtide unique in treating Hepatitis D?

Bulevirtide is unique because it is a first-in-class entry inhibitor that blocks the entry of hepatitis B and D viruses into liver cells, offering a new approach compared to the limited existing option of interferon alpha, which rarely cures the infection. ^{1 2 3 4 8}

What is the purpose of this trial?

This trial is testing bulevirtide, a medication for people with chronic hepatitis delta, a tough-to-treat liver infection. Bulevirtide works by stopping the virus from entering liver cells. The study compares different treatment timings to see which is more effective. Bulevirtide was approved in the European Union for treating chronic hepatitis delta virus (HDV) infection.

Research Team

Gilead Medical Monitor

Principal Investigator

Gilead Sciences

Eligibility Criteria

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

Positive PCR results for serum/plasma HDV RNA at screening

Alanine transaminase level > 1 x upper limit of normal (ULN), but less than 10 x ULN

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

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

Treatment Details

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.

Participant Groups

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

After an observational period of 48 weeks, participants will receive delayed 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

Findings from Research

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]

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, 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Bulevirtide: First Approval. [2021]

2. United States 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Clinical effects of NTCP-inhibitor myrcludex B. [2021]

6. Netherlands 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. [2020]

7. Switzerland 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. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Treating hepatitis D with bulevirtide - Real-world experience from 114 patients. [2023]