Study to Assess Efficacy and Safety of Bulevirtide in Participants With Chronic Hepatitis Delta (CHD)

NCT03852719 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: MYR3012019-001213-17
• Study Type: interventional
• Target: 150
• Locations: 5 countries
• Sites: 19

Brief Summary

The primary objective of this study is to evaluate the efficacy of bulevirtide administered subcutaneously (SC) for 48 weeks at a dose of 2 mg or 10 mg once daily for treatment of chronic hepatitis delta (CHD) in comparison to delayed treatment. The main goal of this study is to determine the effectiveness of bulevirtide in participants randomized to bulevirtide 2 mg or 10 mg once daily SC as compared to participants randomized to delayed treatment for 48 weeks. Treatment will continue through Week 144 (participants randomized to delayed treatment will change to bulevirtide 10 mg once daily SC after Week 48 through Week 144). All participants will be followed off-treatment for an additional 96 weeks.

Conditions

Chronic Hepatitis Delta

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Combined Response at Week 48

  Combined response was defined as fulfilment of two conditions simultaneously: Undetectable (\< lower limit of quantification (LLOQ, target not detected)) HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline; and ALT normalization.

  Week 48

Secondary Outcomes (10)

• Percentage of Participants With Undetectable HDV RNA at Week 48

  Week 48

• Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48

  Week 48

• Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 48

  Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 48

• Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 96

  Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 96

• Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 144

  Baseline, Week 144

Study Arms (3)

Delayed Treatment/Bulevirtide 10 mg/day

EXPERIMENTAL

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).

Drug: Bulevirtide

Bulevirtide 2 mg/day

EXPERIMENTAL

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

Drug: Bulevirtide

Bulevirtide 10 mg/day

EXPERIMENTAL

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

Drug: Bulevirtide

Interventions

Bulevirtide DRUG

Administered via SC injections

Also known as: Myrcludex B, Hepcludex®

Bulevirtide 10 mg/day; Bulevirtide 2 mg/day; Delayed Treatment/Bulevirtide 10 mg/day

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Positive serum anti-hepatitis delta virus (HDV) antibody results or polymerase chain reaction (PCR) results for serum/ plasma HDV ribonucleic acid (RNA) for at least 6 months before screening.
• 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.
• Serum albumin \> 28 g/L.
• Negative urine pregnancy test for females of childbearing potential.
• Postmenopausal for at least 2 years, or
• Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or
• Abstinence from heterosexual intercourse throughout the study, or
• Willingness to use highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive) throughout the study and for 3 months after the last dose of the study medication for individuals discontinued during the treatment period.
• Individuals 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) and not to donate sperm throughout the study and for 3 months after the last dose of the study medication for individuals discontinued during the treatment period.

You may not qualify if:

• Child-Pugh hepatic insufficiency score over 7 points. Uncomplicated oesophageal varices allowed; Individuals with current bleeding or ligation, or history of bleeding or ligation within the last 2 years are excluded.
• Hepatitis C virus (HCV) or uncontrolled human immunodeficiency virus (HIV) coinfection. Individuals with HCV antibodies can be enrolled, if screening HCV RNA test is negative. Individuals with HIV infection can be enrolled if cluster of differentiation (CD4+) cell counts are \>500/mL and HIV RNA is below limit of detection for at least 12 months.
• Creatinine clearance \< 60 mL/min as estimated using Cockcroft-Gault formula.
• Total bilirubin ≥ 34.2 µmol/L. (Individuals with higher total bilirubin values may be included after the consultation with the Study Medical Monitor, if such elevation can be clearly attributed to Gilbert's syndrome associated with low-grade hyperbilirubinemia.)
• Evidence of an active or suspected malignancy or a history of malignancy, or an untreated pre-malignancy disorder within the last 5 years (with the exception of successfully treated carcinoma of the cervix in situ and successfully treated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior to screening \[and no more than 3 excised skin cancer within the last 5 years prior to screening\]) or history of hepatic carcinoma.
• Systemic connective tissue disorders.
• New York Heart Association (NYHA) class III-IV congestive heart failure.
• Individuals with uncontrolled arterial hypertension: systolic blood pressure \> 150 mm Hg and/ or diastolic blood pressure \> 100 mm Hg at Screening.
• Previous or unstable concurrent diseases or conditions that prevent individual's enrolment into the study.
• Individuals with mental disorders or social circumstances that preclude them from following protocol requirements.
• Current or previous (within last 2 years) decompensated liver disease, including coagulopathy, hepatic encephalopathy and esophageal varices hemorrhage.
• One or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.). Gilbert's syndrome, a benign disorder associated with low-grade hyperbilirubinemia, will not exclude individuals from participation in this trial. Autoimmune hepatitis stigmata attributed to HDV infection in the opinion of the investigator are allowed.
• White blood cells (WBC) count \< 3000 cells/mm\^3 (\<1500 if African individuals).
• Neutrophil count \< 1500 cells/mm\^3 (\<1000 if African individuals).
• Platelet count \< 60,000 cells/mm\^3.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (19)

New York University School of Medicine, an administrative unit of New York University, an education corporation

New York, New York, 10016, United States

Location

Cornell University Well Madical College

New York, New York, 10021, United States

Location

Universitätsklinikum Essen (AoR), Klinik für Gastroenterologie und Hepatologie

Essen, Germany

Location

Universitätsklinikum Frankfurt Medizinische Klinik 1

Frankfurt am Main, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, Germany

Location

Heidelberg University Hospital, Departament of Gastroenterology, Infectious Diseases, Intoxication

Heidelberg, Germany

Location

Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Università di Modena e Reggio Emilia- Ospedale Civile S.

Modena, Italy

Location

U.O. Epatologia - Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

State Budgetary Educational Institution of Higher Professional Education "South Ural State Medical University" of the Ministry of Healthcare of the Russian Federation

Chelyabinsk, Russia

Location

Specialized clinical Infectious diseases Hospital

Krasnodar, Russia

Location

Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance

Moscow, Russia

Location

Federal State Budgetary Institution National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation

Moscow, Russia

Location

LLC"Clinic of Modern Medicine"

Moscow, Russia

Location

Moscow Regional Scientific and Research Clinical Institute

Moscow, Russia

Location

LLC Medical Company "Hepatolog"

Samara, Russia

Location

Stavropol Regional Hospital

Stavropol, Russia

Location

Karolinska University Hospital Huddinge, Dept of Infectious Diseases

Stockholm, Sweden

Location

Related Publications (13)

• Wedemeyer H, Aleman S, Andreone P, Blank A, Brunetto M, Bogomolov P, et al. Bulevirtide Monotherapy at Low and High Doses in Patients With Chronic Hepatitis Delta: 24 Weeks Interim Data of the Phase 3 MYR301 Study [Poster 2730]. European Association for the Study of the Liver (EASL): The Digital International Liver Congress; 2021 23-26 June.

  BACKGROUND

• Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, et al. Efficacy and Safety of Bulevirtide Monotherapy Given at 2 mg or 10 mg Dose Level Once Daily for Treatment of Chronic Hepatitis Delta: Week 48 Primary Endpoint Results From a Phase 3 Randomized, Multicenter, Parallel Design Study [Oral Presentation 509]. EASL The International Liver Congress; 2022 22-26 June; London, UK.

  BACKGROUND

• Lampertico P, Roulot D, Wedemeyer H. Bulevirtide with or without pegIFNalpha for patients with compensated chronic hepatitis delta: From clinical trials to real-world studies. J Hepatol. 2022 Nov;77(5):1422-1430. doi: 10.1016/j.jhep.2022.06.010. Epub 2022 Jun 22.

  PMID: 35752223 BACKGROUND

• Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, et al. 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. [Oral Presentation OS-068]. EASL The International Liver Congress; 2023 21-24 June; Vienna, AUS.

  BACKGROUND

• Wedemeyer H, Aleman S, Brunetto MR, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Manuilov D, Suri V, An Q, Da B, Flaherty J, Osinusi A, Liu Y, Merle U, Schulze Zur Wiesch J, Zeuzem S, Ciesek S, Cornberg M, Lampertico P; MYR 301 Study Group. A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D. N Engl J Med. 2023 Jul 6;389(1):22-32. doi: 10.1056/NEJMoa2213429. Epub 2023 Jun 22.

  PMID: 37345876 BACKGROUND

• Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Ciesek S, Manuilov D, Mercier RC, Da BL, Chee GM, Li M, Flaherty JF, Lau AH, Osinusi A, Schulze Zur Wiesch J, Cornberg M, Zeuzem S, Lampertico P. Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial. J Hepatol. 2024 Oct;81(4):621-629. doi: 10.1016/j.jhep.2024.05.001. Epub 2024 May 9.

  PMID: 38734383 BACKGROUND

• Aleman S, Brunetto M, Blank A et al. Efficacy and Safety of Bulevirtide Monotherapy for Chronic Hepatitis Delta: Posttreatment Results Through 48 Weeks After the End of Treatment From an Interim Analysis of a Randomized Phase 3 Study, MYR301; The Liver Meeting, American Association for the Study of Liver Diseases; 2024 15-19 November; San Diego, USA.

  BACKGROUND

• Wedemeyer H, Aleman S, Blank A et al. Final results of MYR301: A Randomised Phase 3 Study Evaluating the Efficacy and Safety of up to 144 Weeks of Bulevirtide Monotherapy For Chronic Hepatitis Delta and 96 Weeks of Posttreatment Follow-up. EASL The International Liver Congress; 2025 7-10 May, Amsterdam, Netherlands.

  BACKGROUND

• Wong RJ, Gish RG, Jacobson IM, Lim JK, Rock M, Kinyik-Merena C, Ma H, Smith N, Kim C. Impact of Double Reflex Testing and Linkage to Treatment on Clinical Outcomes of Chronic Hepatitis Delta Virus Infection in the United States. J Viral Hepat. 2026 Jan;33(1):e70119. doi: 10.1111/jvh.70119.

  PMID: 41405233 DERIVED

• Asselah T, Lampertico P, Aleman S, Bourliere M, Streinu-Cercel A, Bogomolov P, Morozov V, Stepanova T, Lazar S, Manuilov D, Mercier RC, Tseng S, Ye L, Flaherty JF, Osinusi A, Da BL, Chee GM, Lau AH, Brunetto MR, Wedemeyer H. Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48. Liver Int. 2025 Apr;45(4):e16174. doi: 10.1111/liv.16174. Epub 2024 Dec 8.

  PMID: 39648559 DERIVED

• Buti M, Wedemeyer H, Aleman S, Chulanov V, Morozov V, Sagalova O, Stepanova T, Gish RG, Lloyd A, Kaushik AM, Suri V, Manuilov D, Osinusi AO, Flaherty JF, Lampertico P. Patient-reported outcomes in chronic hepatitis delta: An exploratory analysis of the phase III MYR301 trial of bulevirtide. J Hepatol. 2025 Jan;82(1):28-36. doi: 10.1016/j.jhep.2024.06.031. Epub 2024 Jul 14.

  PMID: 39009085 DERIVED

• Allweiss L, Volmari A, Suri V, Wallin JJ, Flaherty JF, Manuilov D, Downie B, Lutgehetmann M, Bockmann JH, Urban S, Wedemeyer H, Dandri M. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies. J Hepatol. 2024 Jun;80(6):882-891. doi: 10.1016/j.jhep.2024.01.035. Epub 2024 Feb 8.

  PMID: 38340811 DERIVED

• Hollnberger J, Liu Y, Xu S, Chang S, Martin R, Manhas S, Aeschbacher T, Han B, Yazdi T, May L, Han D, Shornikov A, Flaherty J, Manuilov D, Suri V, Asselah T, Lampertico P, Wedemeyer H, Aleman S, Richards C, Mateo R, Maiorova E, Cihlar T, Mo H, Urban S. No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta. J Hepatol. 2023 Sep;79(3):657-665. doi: 10.1016/j.jhep.2023.04.027. Epub 2023 Apr 27.

  PMID: 37120031 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Hepatitis D, Chronic

Interventions

bulevirtide; myrcludex-B

Condition Hierarchy (Ancestors)

Hepatitis D; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Medical Monitor

  Gilead Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2019
• First Posted: February 25, 2019
• Study Start: April 17, 2019
• Primary Completion: November 26, 2020
• Study Completion: August 8, 2024
• Last Updated: August 22, 2025
• Results First Posted: October 28, 2022

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); US (2); DE (5); IT (3); RU (8)