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

NCT03852433 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MYR2042019-001485-15
• Study Type: interventional
• Target: 175
• Locations: 4 countries
• Sites: 20

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24)

  SVR24 was defined as undetectable hepatitis delta virus (HDV) RNA (HDV RNA value \< lower limit of quantitation \[LLOQ\] with target not detected) at 24 weeks after the scheduled end of treatment (EOT).

  24 weeks after EOT (Week 72 for Arm A and study Week 120 for Arms B, C, and D)

Secondary Outcomes (8)

• Percentage of Participants With Undetectable HDV RNA at Week 48

  Week 48

• Percentage of Participants With Undetectable HDV RNA at Week 96 (Arms B, C, and D Only)

  Week 96

• Percentage of Participants With Combined Response at Week 24 After the Scheduled End of Treatment

  24 weeks after EOT (Week 72 for Arm A and Week 120 for Arms B, C, and D)

• Percentage of Participants With Combined Response at Week 48 After the Scheduled End of Treatment

  48 weeks after EOT (Week 96 for Arm A and Week 144 for Arm B, C, and D)

• Percentage of Participants With Sustained Virological Response 48 After the Scheduled End of Treatment (SVR 48)

  48 weeks after EOT (Week 96 for Arm A; Week 144 for Arms B, C, and D)

Study Arms (4)

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

ACTIVE COMPARATOR

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

Drug: Peginterferon Alfa-2a (PEG-IFN alfa)

Bulevirtide 2 mg/day + PEG-IFN alfa

EXPERIMENTAL

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.

Drug: Bulevirtide; Drug: Peginterferon Alfa-2a (PEG-IFN alfa)

Bulevirtide 10 mg/day + PEG-IFN alfa

EXPERIMENTAL

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.

Drug: Bulevirtide; Drug: Peginterferon Alfa-2a (PEG-IFN alfa)

Bulevirtide 10 mg once a day

EXPERIMENTAL

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

Drug: Bulevirtide

Interventions

Bulevirtide DRUG

Administered via subcutaneous injections

Also known as: Myrcludex B, Hepcludex®

Bulevirtide 10 mg once a day; Bulevirtide 10 mg/day + PEG-IFN alfa; Bulevirtide 2 mg/day + PEG-IFN alfa

Peginterferon Alfa-2a (PEG-IFN alfa) DRUG

Administered via subcutaneous injections

Bulevirtide 10 mg/day + PEG-IFN alfa; Bulevirtide 2 mg/day + PEG-IFN alfa; Pegylated Interferon alfa-2a (PEG-IFN alfa)

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (20)

Hôpital Beaujon-Pavillon Abrami -Sce Hépatologie

Clichy, France

Location

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, France

Location

Hospital Croix Rousee

Lyon, France

Location

Hôpital Saint Joseph Hépato-Gastroentérologie

Marseille, France

Location

CH Pitié-Salpétrière - Hépato-Gastroentérologie

Paris, France

Location

Hôpital Cochin - Unité d'Hépatologie Pavillon Achard

Paris, France

Location

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

Chisinau, Moldova

Location

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

Chisinau, Moldova

Location

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

Bucharest, Romania

Location

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

Bucharest, Romania

Location

"Victor Babes" Centre of Diagnostic and Treatment

Bucharest, Romania

Location

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

Bucharest, Romania

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 Institute of Science "Central Research Institute for Epidemiology" of Federal Service on Consumers 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

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

Moscow, Russia

Location

LLC Medical Company "Hepatolog"

Samara, Russia

Location

Related Publications (6)

• 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.

  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.

  PMID: 34482769 BACKGROUND

• 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.

  PMID: 36712949 BACKGROUND

• 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.

  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.

  PMID: 39648559 DERIVED

• 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.

  PMID: 38842520 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Hepatitis D, Chronic

Interventions

bulevirtide; myrcludex-B; peginterferon alfa-2a

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 2
• 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: May 31, 2019
• Primary Completion: April 5, 2022
• Study Completion: September 28, 2022
• Last Updated: October 8, 2024
• Results First Posted: July 29, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

RO (4); MO (2); FR (6); RU (8)