Study to Assess Efficacy and Safety of Bulevirtide in Combination With Pegylated Interferon Alfa-2a in Participants With Chronic Hepatitis Delta (CHD)

NCT ID: NCT03852433

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2022-09-28

Brief Summary

The primary objective of this study is to evaluate the efficacy of bulevirtide in combination with pegylated interferon in participants with chronic hepatitis delta (CHD).

Conditions

Chronic Hepatitis Delta

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pegylated Interferon alfa-2a (PEG-IFN alfa)

Participants will receive PEG-IFN alfa 180 microgram (mcg) once a week subcutaneously for 48 weeks with additional 48 weeks follow-up.

Group Type: ACTIVE_COMPARATOR

Peginterferon Alfa-2a (PEG-IFN alfa)

Intervention Type: DRUG

Administered via subcutaneous injections

Bulevirtide 2 mg/day + PEG-IFN alfa

Participants will receive bulevirtide 2 mg once a day subcutaneously incombination with PEG-IFN alfa 180 mcg once a week subcutaneously for 48 weeks followed by bulevirtide 2 mg once a day for 48 weeks and additional 48 weeks follow-up.

Group Type: EXPERIMENTAL

Bulevirtide

Intervention Type: DRUG

Administered via subcutaneous injections

Peginterferon Alfa-2a (PEG-IFN alfa)

Intervention Type: DRUG

Administered via subcutaneous injections

Bulevirtide 10 mg/day + PEG-IFN alfa

Participants will receive bulevirtide 10 mg once a day subcutaneously in combination with PEG-IFN alfa 180 mcg once a week subcutaneously for 48 weeks followed by bulevirtide 10 mg once a day for 48 weeks and additional 48 weeks follow-up.

Group Type: EXPERIMENTAL

Bulevirtide

Intervention Type: DRUG

Administered via subcutaneous injections

Peginterferon Alfa-2a (PEG-IFN alfa)

Intervention Type: DRUG

Administered via subcutaneous injections

Bulevirtide 10 mg once a day

Participants will receive bulevirtide 10 mg once a day subcutaneously for 96 weeks with additional 48 weeks follow-up

Group Type: EXPERIMENTAL

Bulevirtide

Intervention Type: DRUG

Administered via subcutaneous injections

Interventions

Bulevirtide

Administered via subcutaneous injections

Intervention Type: DRUG

Peginterferon Alfa-2a (PEG-IFN alfa)

Administered via subcutaneous injections

Intervention Type: DRUG

Other Intervention Names

Myrcludex B; Hepcludex®

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated informed consent form.
• Positive serum 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.
• Thyroid stimulating hormone (TSH) within normal ranges (including on medication for control of thyroid function)
• 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 treatment period, or
• Willingness to use highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive) throughout the treatment period and for 6 months after the last dose of the study medication.
• Male 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 treatment period and for 6 months after the last dose of the study medication.

Exclusion Criteria

• Child-Pugh hepatic insufficiency score of B-C or over 6 points. Note: Child-Pugh hepatic insufficiency score of 6 points is allowed. Only individuals with compensated cirrhosis are allowed. 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 human immunodeficiency virus (HIV) coinfection. Individuals with HCV antibodies can be enrolled, if screening HCV RNA test is negative.
• 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 an untreated pre-malignancy disorder, or a history of malignancy 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 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 individauls 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).
• Absolute neutrophil count < 1500 cells/mm^3 (<1000 if African individuals).
• Platelet count < 90,000 cells/mm^3.
• Haemoglobin < 12 g/dL.
• Use of prohibited psychotropic agents at Screening.
• Use of interferons within 6 months before Screening.
• History of solid organ transplantation.
• Current alcohol abuse or alcohol abuse within 6 months prior to enrolment in this study; current drug addict or history of drug use within 2 years prior to Screening.
• History of disease requiring regular use of systemic glucocorticosteroids (inhalative glucocorticosteroids are allowed) or other immunosuppressants.
• Pregnant or breast-feeding females.
• Participation in another clinical study with investigational drugs within 30 days prior to randomization.
• Receipt of bulevirtide previously, e.g. in clinical trials.
• 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.
• Contraindications, intolerance or hypersensitivity to interferons alfa, genetically engineered E.coli medications, polyethylene glycol or other components of peginterferon alfa-2а.
• Presence or history of severe retinopathy, significant diabetic or hypertensive retinopathy.
• Uncontrolled diabetes mellitus.
• Uncontrolled cardiovascular disorders within 6 months before screening.
• History of autoimmune disorder (e.g. myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, severe psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus)
• Presence or history of significant psychiatric disorder (e.g. severe depression, suicide attempt, severe neurosis or cognitive disorder).
• Presence or history of chronic lung disease with respiratory malfunction.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Medical Monitor

Role: STUDY_CHAIR

Gilead Sciences

Locations

Hôpital Beaujon-Pavillon Abrami -Sce Hépatologie

Clichy, , France

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, , France

Hospital Croix Rousee

Lyon, , France

Hôpital Saint Joseph Hépato-Gastroentérologie

Marseille, , France

CH Pitié-Salpétrière - Hépato-Gastroentérologie

Paris, , France

Hôpital Cochin - Unité d'Hépatologie Pavillon Achard

Paris, , France

Infectious Clinical Hospital "T. Ciorba", Department 4 / Medical University Department of Infectious Diseases

Chisinau, , Moldova

Infectious Clinical Hospital "T. Ciorba", Department 5 / Medical University Department of Infectious Diseases

Chisinau, , Moldova

"Matei Bals" National Institute of Infectious Diseases, Hospital department

Bucharest, , Romania

"Matei Bals" National Institute of Infectious Diseases,Clinical Trials department

Bucharest, , Romania

"Victor Babes" Centre of Diagnostic and Treatment

Bucharest, , Romania

Dr. V. Babes Clinical Hospital of Infectious and Tropical Diseases

Bucharest, , Romania

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

Chelyabinsk, , Russia

Specialized clinical Infectious diseases Hospital

Krasnodar, , Russia

Federal Budget Institute of Science "Central Research Institute for Epidemiology" of Federal Service on Consumers Rights Protection and Human Well-Being Surveillance

Moscow, , Russia

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

Moscow, , Russia

LLC"Clinic of Modern Medicine"

Moscow, , Russia

Moscow Regional Scientific and Research Clinical Institute

Moscow, , Russia

N.V.Sklifosovsky Scientific Research Institute of Emergency care of the Moscow Healthcare Department

Moscow, , Russia

LLC Medical Company "Hepatolog"

Samara, , Russia

Countries

France; Moldova; Romania; Russia

References

Asselah T, Arama SS, Bogomolov P, Bourliere M, Fontaine H, Gherlan GS, et al. Safety and Efficacy of Bulevirtide Monotherapy and in Combination with Peginterferon Alfa-2a in Patients with Chronic Hepatitis Delta: 24 Weeks Interim Data of MYR204 Phase 2b Study [Presentation]. European Association for the Study of the Liver (EASL): The Digital International Liver Congress; 2021 23-26 June.

Reference Type: BACKGROUND

Asif B, Koh C. Hepatitis D virus (HDV): investigational therapeutic agents in clinical trials. Expert Opin Investig Drugs. 2022 Sep;31(9):905-920. doi: 10.1080/13543784.2021.1977795. Epub 2021 Oct 1.

Reference Type: BACKGROUND

PMID: 34482769 (View on PubMed)

Soriano V, Moreno-Torres V, Trevino A, Corral O, de Mendoza C. Bulevirtide in the Treatment of Hepatitis Delta: Drug Discovery, Clinical Development and Place in Therapy. Drug Des Devel Ther. 2023 Jan 21;17:155-166. doi: 10.2147/DDDT.S379964. eCollection 2023.

Reference Type: BACKGROUND

PMID: 36712949 (View on PubMed)

Asselah T, Lampertico P, Wedemeyer H, Streinu-Cercel A, Pantea V, Lazar S, et al. Efficacy and Safety of Bulevirtide in Combination with Pegylated Interferon alfa-2a in Patients with Chronic Hepatitis Delta: Primary Endpoint Results from a Phase 2b Open-Label, Randomized, Multicenter Study MYR204. [Poster #5009]. AASLD - The Liver Meeting; 2023 November 10-24; Boston, MA.

Reference Type: BACKGROUND

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.

Reference Type: DERIVED

PMID: 39648559 (View on PubMed)

Asselah T, Chulanov V, Lampertico P, Wedemeyer H, Streinu-Cercel A, Pantea V, Lazar S, Placinta G, Gherlan GS, Bogomolov P, Stepanova T, Morozov V, Syutkin V, Sagalova O, Manuilov D, Mercier RC, Ye L, Da BL, Chee G, Lau AH, Osinusi A, Bourliere M, Ratziu V, Pol S, Hilleret MN, Zoulim F. Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D. N Engl J Med. 2024 Jul 11;391(2):133-143. doi: 10.1056/NEJMoa2314134. Epub 2024 Jun 6.

Reference Type: DERIVED

PMID: 38842520 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=MYR%20204

Gilead Clinical Trials Website

Other Identifiers

2019-001485-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MYR204

Identifier Type: -

Identifier Source: org_study_id