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Phase 3 Study of Bulevirtide in Patients With CHD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03852719
Recruitment Status : Active, not recruiting
First Posted : February 25, 2019
Last Update Posted : March 3, 2020
Sponsor:
Collaborator:
Hepatera Ltd.
Information provided by (Responsible Party):
MYR GmbH

Brief Summary:
This study is to evaluate the efficacy of Bulevirtide administered subcutaneously for 48 weeks at a dose of 2 mg or 10 mg once daily for treatment of chronic hepatitis delta in comparison to delayed treatment.

Condition or disease Intervention/treatment Phase
Hepatitis D, Chronic Drug: Bulevirtide Phase 3

Detailed Description:

This study is designed to assess the long-term efficacy and safety of Bulevirtide in patients with chronic hepatitis Delta (CHD). Primary efficacy and safety data will be assessed at week 48, when Bulevirtide at 2 and 10 mg daily doses will be compared with delayed treatment. After week 48 patients of delayed treatment arm in this study will be switched to Bulevirtide at 10 mg daily dose for additional 96 weeks. The total duration of treatment period in this phase 3 study will be 144 weeks.

The period of 48 weeks of no-treatment in this phase 3 study is justified by the absence of any approved therapy or an effective treatment regime for the respective indication; furthermore, patients of the delayed treatment arm shall receive a 96 weeks treatment of the 10 mg Bulevirtide after the assessment of the primary endpoint.

After the analysis of the primary endpoint, the treatment will be continued for the period of up to 3 years to investigate the optimal therapy duration. During the treatment free follow up period, the possibility of the sustained virologic response shall be assessed. Whereas the study is not powered to investigate the difference in clinical outcomes such as death, cirrhosis decompensation or liver transplantation, those endpoints will be captured, and the information will be used in the overall concept of the clinical confirmation.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter, Open-label, Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized Phase 3 Clinical Study to Assess Efficacy and Safety of Bulevirtide in Patients With Chronic Hepatitis Delta
Actual Study Start Date : April 17, 2019
Estimated Primary Completion Date : February 28, 2025
Estimated Study Completion Date : February 28, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A - Bulevirtide 10 mg/day
Observation for 48 weeks followed by Bulevirtide 10 mg/day for 96 weeks and further follow-up period for 96 weeks
Drug: Bulevirtide
daily subcutaneus injections
Other Name: Myrcludex B

Experimental: Arm B - Bulevirtide 2 mg/day
Bulevirtide 2 mg/day for 144 weeks with a further follow-up period of 96 weeks
Drug: Bulevirtide
daily subcutaneus injections
Other Name: Myrcludex B

Experimental: Arm C - Bulevirtide 10 mg/day
Bulevirtide 10 mg/day for 144 weeks with a further follow-up period of 96 weeks
Drug: Bulevirtide
daily subcutaneus injections
Other Name: Myrcludex B




Primary Outcome Measures :
  1. Combined response: Undetectable (< LLoD) hepatitis Delta virus ribonucleic acid (HDV RNA) or decrease by ≥ 2 log10 IU/ml from baseline and ALT normalization [ Time Frame: 48 weeks ]
    Combined response: Undetectable (< LLoD) hepatitis Delta virus ribonucleic


Secondary Outcome Measures :
  1. Undetectable HDV RNA at week 48 [ Time Frame: 48 weeks ]
    Undetectable HDV RNA at week 48

  2. ALT normalization at week 48 [ Time Frame: 48 weeks ]
    ALT normalization at week 48

  3. Undetectable HDV RNA 24 weeks after scheduled end of treatment (sustained virological response) [ Time Frame: 24 weeks ]
    Undetectable HDV RNA 24 weeks after scheduled end of treatment (sustained

  4. Undetectable HDV RNA 48 weeks after scheduled end of treatment (sustained virological response) [ Time Frame: 48 weeks ]
    Undetectable HDV RNA 48 weeks after scheduled end of treatment (sustained

  5. Change from baseline in liver stiffness as measured by elastography at week 48, 96, 144, 192 and 240 [ Time Frame: 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks ]
    Change from baseline in liver stiffness as measured by elastography at week



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of signed and dated informed consent form.
  2. Male or female, aged 18-65 years (inclusive).
  3. Positive serum anti-HDV antibody results or PCR results for serum/ plasma HDV RNA for at least 6 months before Screening.
  4. Positive PCR results for serum/ plasma HDV RNA at Screening.
  5. Alanine transaminase level >1 x ULN, but less than 10 x ULN.
  6. Serum albumin >2.8 mg/dL.
  7. Negative urine pregnancy test for females of childbearing potential.
  8. Inclusion criteria for female subjects:

    • 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.
  9. Male subjects 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.

Exclusion Criteria:

  1. Child-Pugh hepatic insufficiency score over 7 points. Uncomplicated oesophageal varices allowed; Subjects with current bleeding or ligation, or history of bleeding or ligation within the last 2 years are excluded.
  2. HCV or uncontrolled HIV coinfection. Subjects with HCV antibodies can be enrolled, if screening HCV RNA test is negative. Subjects with HIV infection can be enrolled if 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. [Patients 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. NYHA (New York Heart Association) class III-IV congestive heart failure.
  8. Patients with uncontrolled arterial hypertension within 3 months prior to start of clinical phase of the study. [Patients with systolic blood pressure > 150 mm Hg or diastolic blood pressure > 100 mm Hg despite antihypertensive treatment at Screening can be included after the confirmation of the Study Medical Monitor].
  9. Previous or unstable concurrent diseases or conditions that prevent subject's enrolment into the study.
  10. Patients 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.
  13. White blood cells (WBC) count < 3000 cells/mm3 (<1500 if African patients).
  14. Neutrophil count < 1500 cells/mm3 (<1000 if African patients).
  15. Platelet count < 60,000 cells/mm3.
  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: Patients with medical contraindication for liver biopsy are allowed to participate in this study. Such patients will exempt from liver biopsy requirements in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03852719


Locations
Show Show 18 study locations
Sponsors and Collaborators
MYR GmbH
Hepatera Ltd.
Investigators
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Principal Investigator: Pavel Bogomolov, MD Limited Liability Company "Clinic of Modern Medicine"
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Responsible Party: MYR GmbH
ClinicalTrials.gov Identifier: NCT03852719    
Other Study ID Numbers: MYR 301
First Posted: February 25, 2019    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Hepatitis D
Hepatitis D, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Hepatitis, Chronic