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Chronic Hepatitis DeltaPhase 2NCT03852433

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

A Phase 2 study testing Bulevirtide and Peginterferon Alfa-2a (PEG-IFN alfa) in people with Chronic Hepatitis Delta, run by Gilead Sciences at 20 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Hepatitis Delta
What is being tested?
Bulevirtide and Peginterferon Alfa-2a (PEG-IFN alfa)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
20 sitesin 4 countries
Study dates
31 May 2019to 28 Sep 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

20 sites in 4 countries.

20 sites in 4 countries

Russia8 sites

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

    Chelyabinsk

  • Specialized clinical Infectious diseases Hospital

    Krasnodar

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

    Moscow

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

    Moscow

  • LLC"Clinic of Modern Medicine"

    Moscow

  • Moscow Regional Scientific and Research Clinical Institute

    Moscow

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

    Moscow

  • LLC Medical Company "Hepatolog"

    Samara

Other trials in Russia

France6 sites

  • Hôpital Beaujon-Pavillon Abrami -Sce Hépatologie

    Clichy

  • Centre Hospitalier Universitaire Grenoble Alpes

    Grenoble

  • Hospital Croix Rousee

    Lyon

  • Hôpital Saint Joseph Hépato-Gastroentérologie

    Marseille

  • CH Pitié-Salpétrière - Hépato-Gastroentérologie

    Paris

  • Hôpital Cochin - Unité d'Hépatologie Pavillon Achard

    Paris

Other trials in France

Romania4 sites

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

    Bucharest

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

    Bucharest

  • "Victor Babes" Centre of Diagnostic and Treatment

    Bucharest

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

    Bucharest

Other trials in Romania

Moldova2 sites

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

    Chisinau

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

    Chisinau

Other trials in Moldova

About this study

Official title: A Multicenter, Open-label, Randomized Phase 2b Clinical Study to Assess Efficacy and Safety of Bulevirtide in Combination With Pegylated Interferon Alfa-2a in Patients With Chronic Hepatitis Delta

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).

Being tested
Bulevirtide, Peginterferon Alfa-2a (PEG-IFN alfa)
Medical subject headings
Hepatitis D, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BulevirtideDrug

    Also called Myrcludex B, Hepcludex®

    Administered via subcutaneous injections

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

    Administered via subcutaneous injections

Study groups in NCT03852433
Study groupRoleWhat they receive
Pegylated Interferon alfa-2a (PEG-IFN alfa)Active comparatorParticipants will receive PEG-IFN alfa 180 microgram (mcg) once a week subcutaneously for 48 weeks with additional 48 weeks follow-up.
Receives: Drug: Peginterferon Alfa-2a (PEG-IFN alfa)
Bulevirtide 2 mg/day + PEG-IFN alfaExperimentalParticipants 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.
Receives: Drug: Bulevirtide; Drug: Peginterferon Alfa-2a (PEG-IFN alfa)
Bulevirtide 10 mg/day + PEG-IFN alfaExperimentalParticipants 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.
Receives: Drug: Bulevirtide; Drug: Peginterferon Alfa-2a (PEG-IFN alfa)
Bulevirtide 10 mg once a dayExperimentalParticipants will receive bulevirtide 10 mg once a day subcutaneously for 96 weeks with additional 48 weeks follow-up
Receives: Drug: Bulevirtide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

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

Secondary outcomes (8)

  1. 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.

    Measured: Week 48

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

    Undetectable HDV RNA at Week 96 means undetectable (< LLOQ, target not detected) HDV RNA at Week 96.

    Measured: Week 96

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

    Combined response was defined as fulfilment of 2 conditions simultaneously: 1) undetectable HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline, alanine aminotransferase (ALT) normalization, 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]).

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

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

    Combined response is defined as fulfilment of 2 conditions simultaneously: 1) undetectable HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline, ALT normalization, 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]).

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

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

    SVR 48 is defined as undetectable hepatitis delta virus (HDV) RNA (HDV RNA value < lower limit of quantitation [LLOQ] with target not detected) at 48 weeks after the scheduled end of treatment.

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

  6. Change From Baseline in Liver Stiffness as Measured by Elastography at Week 48

    The mixed-effects models for repeated measurements (MMRM) model was used for analysis.

    Measured: Baseline, Week 48

  7. Change From Baseline in Liver Stiffness as Measured by Elastography at Week 96

    The MMRM model was used for analysis.

    Measured: Baseline, Week 96

  8. Change From Baseline in Liver Stiffness as Measured by Elastography at Week 144

    The MMRM model was used for analysis.

    Measured: Baseline, 48 weeks after EOT (Week 96 for Arm A and study Week 144 for Arms B, C, and D)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2019
  2. Study start31 May 2019
  3. Primary completion5 Apr 2022
  4. Study completion28 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03852433
Sponsor's protocol ID
MYR204
Other IDs
2019-001485-15, 2019
Status last verified
Sep 2024
First submitted
21 Feb 2019
Last updated
8 Oct 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

  • 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.

    PubMed 34482769

  • 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.

    PubMed 36712949

  • 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.

  • 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.

    PubMed 39648559

  • 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.

    PubMed 38842520

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bulevirtide and Peginterferon Alfa-2a (PEG-IFN alfa) in people with Chronic Hepatitis Delta, run by Gilead Sciences at 20 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Russia, France, Romania, Moldova. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Sustained Virological Response at Week 24 After the Scheduled End of Treatment (SVR24) (time frame: 24 weeks after EOT (Week 72 for Arm A and study Week 120 for Arms B, C, and D)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03852433, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2024.

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