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

A Multicenter, Open-label, Randomized Phase 3 Clinical Study to Assess Efficacy and Safety of Bulevirtide in Patients With Chronic Hepatitis Delta

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis Delta
• Intervention / Treatment: Drug: Bulevirtide

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany
    • Universitätsklinikum Essen (AoR), Klinik für Gastroenterologie und Hepatologie
  • Frankfurt am Main, Germany
    • Universitätsklinikum Frankfurt Medizinische Klinik 1
  • Hamburg, Germany
    • Universitatsklinikum Hamburg-Eppendorf
  • Hannover, Germany
    • Medizinische Hochschule Hannover, Klinik fur Gastroenterologie, Hepatologie und Endokrinologie
  • Heidelberg, Germany
    • Heidelberg University Hospital, Departament of Gastroenterology, Infectious Diseases, Intoxication
• Italy
  • Milan, Italy
    • Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Modena, Italy
    • Università di Modena e Reggio Emilia- Ospedale Civile S.
  • Pisa, Italy
    • U.O. Epatologia - Azienda Ospedaliero Universitaria Pisana
• Russian Federation
  • Chelyabinsk, Russian Federation
    • State Budgetary Educational Institution of Higher Professional Education "South Ural State Medical University" of the Ministry of Healthcare of the Russian Federation
  • Krasnodar, Russian Federation
    • Specialized Clinical Infectious Diseases Hospital
  • Moscow, Russian Federation
    • Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance
  • Moscow, Russian Federation
    • Federal State Budgetary Institution National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation
  • Moscow, Russian Federation
    • LLC"Clinic of Modern Medicine"
  • Moscow, Russian Federation
    • Moscow Regional Scientific and Research Clinical Institute
  • Samara, Russian Federation
    • LLC Medical Company "Hepatolog"
  • Stavropol', Russian Federation
    • Stavropol Regional Hospital
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital Huddinge, Dept of Infectious Diseases
• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine, an administrative unit of New York University, an education corporation
    • New York, New York, United States, 10021
      • Cornell University Well Madical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. 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.
3. Positive PCR results for serum/plasma HDV RNA at screening.
4. Alanine transaminase level > 1 x upper limit of normal (ULN), but less than 10 x ULN.
5. Serum albumin > 28 g/L.
6. Negative urine pregnancy test for females of childbearing potential.

7. Inclusion criteria for females:

   • 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.
8. 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.

Exclusion Criteria:

1. 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.
2. 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.
3. Creatinine clearance < 60 mL/min as estimated using Cockcroft-Gault formula.
4. 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.)
5. 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.
6. Systemic connective tissue disorders.
7. New York Heart Association (NYHA) class III-IV congestive heart failure.
8. Individuals with uncontrolled arterial hypertension: systolic blood pressure > 150 mm Hg and/ or diastolic blood pressure > 100 mm Hg at Screening.
9. Previous or unstable concurrent diseases or conditions that prevent individual's enrolment into the study.
10. Individuals with mental disorders or social circumstances that preclude them from following protocol requirements.
11. Current or previous (within last 2 years) decompensated liver disease, including coagulopathy, hepatic encephalopathy and esophageal varices hemorrhage.
12. 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.
13. White blood cells (WBC) count < 3000 cells/mm^3 (<1500 if African individuals).
14. Neutrophil count < 1500 cells/mm^3 (<1000 if African individuals).
15. Platelet count < 60,000 cells/mm^3.
16. Use of prohibited psychotropic agents at Screening.
17. Use of interferons within 6 months before Screening.
18. History of solid organ transplantation.
19. Current alcohol abuse or alcohol abuse within 6 months prior to enrolment in this study; past or current drug addict.
20. History of disease requiring regular use of systemic glucocorticosteroids (inhalative glucocorticosteroids are allowed) or other immunosuppressants.
21. Pregnant or breast-feeding females.
22. Participation in another clinical study with investigational drugs within 30 days prior to randomization.
23. Receipt of bulevirtide previously, e.g. in clinical trials.
24. Inability to follow protocol requirements and undergo all protocol procedures. NOTE: Individuals with medical contraindication for liver biopsy are allowed to participate in this study. Such individuals will exempt from liver biopsy requirements in this study.

Individuals receiving prohibited treatment at Screening cannot be included into the study unless this treatment is withdrawn prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bulevirtide 2 mg/day; 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; Administered via SC injections; Other Names: Myrcludex B; Hepcludex®
Experimental: Bulevirtide 10 mg/day; 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; Administered via SC injections; Other Names: Myrcludex B; Hepcludex®
Experimental: Delayed Treatment/Bulevirtide 10 mg/day; 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; Administered via SC injections; Other Names: Myrcludex B; Hepcludex®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Undetectable HDV RNA at Week 48	Undetectable HDV RNA at Week 48 means undetectable (< LLOQ, target not detected) HDV RNA at Week 48.	Week 48
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48	ALT normalization was defined as an ALT value within the normal range, based on the central laboratories [Russian sites: ≤ 31 U/L for females and ≤ 41 U/L for males; all other sites: ≤ 34 U/L for females and ≤ 49 U/L for males])	Week 48
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 48	ANCOVA was used for analysis.	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	Mixed model for repeated measurements (MMRM) was used for analysis.	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	MMRM was used for analysis.	Baseline, Week 144
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event (AE) by Week 144	An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.	Delayed Treatment/Bulevirtide 10 mg/day arm: Week 48 up to Week 144; Bulevirtide 2mg/day and 10 mg/day arms: First dose date up to Week 144
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 192	MMRM was used for analysis.	Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 192
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 240	MMRM was used for analysis.	Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 240
Percentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)	Undetectable HDV RNA 24 Weeks after Scheduled End of Treatment means undetectable (< LLOQ, target not detected) HDV RNA at Week 168	Week 168
Percentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)	Undetectable HDV RNA 48 Weeks after Scheduled End of Treatment means undetectable (< LLOQ, target not detected) HDV RNA at Week 192	Week 192

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Chair: Gilead Medical Monitor, Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Actual): November 26, 2020
• Study Completion (Actual): August 8, 2024

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: February 21, 2019
• First Posted (Actual): February 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis A; Hepatitis; Hepatitis, Chronic; Hepatitis D
• Other Study ID Numbers: MYR301; 2019-001213-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No