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

September 12, 2023 updated by: Gilead Sciences

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 for treatment of chronic hepatitis delta (CHD) in comparison to delayed treatment.

Study Overview

Status

Active, not recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Essen, Germany
        • Universitätsklinikum Essen (AoR), Klinik für Gastroenterologie und Hepatologie
      • Frankfurt am Main, Germany
        • Universitätsklinikum Frankfurt Medizinische Klinik 1
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Hannover, Germany
        • Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
      • Heidelberg, Germany
        • Heidelberg University Hospital, Departament of Gastroenterology, Infectious Diseases, Intoxication
      • 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
      • 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
      • Stockholm, Sweden
        • Karolinska University Hospital Huddinge, Dept of Infectious Diseases
    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 participants 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 participants 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. (Participants 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. Participants 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. Participants 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 patients 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 participants).
  14. Neutrophil count < 1500 cells/mm^3 (<1000 if African participants).
  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: Participants with medical contraindication for liver biopsy are allowed to participate in this study. Such participants 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Delayed Treatment
Participants will receive delayed treatment with bulevirtide 10 mg/day subcutaneously (SC) for 96 weeks after an observational period of 48 weeks.
Administered via SC injections
Other Names:
  • Myrcludex B
  • Hepcludex®
Experimental: Bulevirtide 2 mg/day
Participants will receive bulevirtide 2 mg/day SC for 144 weeks.
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.
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
Time Frame: 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
Time Frame: Week 48
Week 48
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Percentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)
Time Frame: Week 168
Week 168
Percentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)
Time Frame: Week 192
Week 192
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 144
Time Frame: Baseline, Week 144
Baseline, Week 144
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 192
Time Frame: Baseline, Week 192
Baseline, Week 192
Change From Baseline in Liver Stiffness, as Measured by Elastography at Weeks 240
Time Frame: Baseline, Week 240
Baseline, Week 240
Percentage of Participants With Alanine Aminotransaminase (ALT) Normalization at Week 48
Time Frame: 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
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE) (Week 48)
Time Frame: First dose date up to Week 48
An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily had 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.
First dose date up to Week 48
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE) (Week 96)
Time Frame: Delayed Treatment arm: Week 48 up to Week 96; Bulevertide 2mg/day and 10 mg/day arms: First dose date up to Week 96
An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily had 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 arm: Week 48 up to Week 96; Bulevertide 2mg/day and 10 mg/day arms: First dose date up to Week 96
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE) (Week 144)
Time Frame: First dose date up to Week 144.
An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily had 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.
First dose date up to Week 144.
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 96
Time Frame: Baseline, Week 96
A mixed-effects model for repeated measures (MMRM) was used to test null hypotheses of no difference compared to the control group. Change from baseline in liver stiffness was the dependent variable using data for all post-baseline analysis visits up to Week 96. The model included treatment, region, presence of cirrhosis, visit and treatment-by-visit interaction as fixed-effect factors, and baseline Liver stiffness as covariate
Baseline, Week 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: Gilead Medical Monitor, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2019

Primary Completion (Actual)

November 26, 2020

Study Completion (Estimated)

July 1, 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)

October 5, 2023

Last Update Submitted That Met QC Criteria

September 12, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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