Phase 2b Study of Bulevirtide (With Peginterferon Alfa-2a) in Patients With CHD
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| ClinicalTrials.gov Identifier: NCT03852433 |
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Recruitment Status :
Recruiting
First Posted : February 25, 2019
Last Update Posted : December 19, 2019
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Sponsor:
MYR GmbH
Collaborator:
Hepatera Ltd.
Information provided by (Responsible Party):
MYR GmbH
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Brief Summary:
This is Phase 2b Clinical Study to Assess Efficacy and Safety of Bulevirtide in Combination with Pegylated Interferon alfa-2a in Patients with Chronic Hepatitis Delta
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis D, Chronic | Drug: Bulevirtide Drug: Peginterferon Alfa-2a | Phase 2 |
A Multicenter, Open-label, Randomized Phase 2b Clinical Study. Approximately 25 study sites in approximately 4 countries globally which may include Russia, France, Moldova, Romania.
There is currently no approved drug for treatment of chronic hepatitis Delta (CHD). Pegylated interferon alfa -2a (PEG-IFN alfa) is approved for treatment of chronic hepatitis И virus (HBV) infection which is required for the propagation of hepatitis Delta virus (HDV), and used to treat patients with HDV infection with evidence of some virologic efficacy. Interferon has a complex mode of action, whereas direct antiviral effects and immunomodulatory mechanisms have been described. Bulevirtide is an entry inhibitor has demonstrated significant virologic and biochemical activity in patients with HDV infection during the Phase 2 clinical trials. A combination of the both drugs demonstrated significant synergistic effects in the 201 clinical trial. It is therefore warranted to further investigate the combination therapy with the aim of improvement of sustained virologic response rates.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 175 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 2b Clinical Study to Assess Efficacy and Safety of Bulevirtide in Combination With Pegylated Interferon Alfa-2a in Patients With Chronic Hepatitis Delta |
| Actual Study Start Date : | May 31, 2019 |
| Estimated Primary Completion Date : | February 28, 2023 |
| Estimated Study Completion Date : | February 28, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Peginterferon Alfa-2a
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm A - Peginterferon alfa-2a
Peginterferon alfa-2a for 48 weeks with additional 48 weeks follow up
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Drug: Peginterferon Alfa-2a
weekly subcutaneus injections at a dose 180 mcg |
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Experimental: Arm B - Bulevirtide 2 mg/day
Bulevirtide 2 mg/day in combination with peginterferon alfa-2a for 48 weeks followed by Bulevirtide 2 mg/day for 48 weeks and additional 48 weeks follow up
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Drug: Bulevirtide
daily subcutaneus injections
Other Name: Myrcludex B Drug: Peginterferon Alfa-2a weekly subcutaneus injections at a dose 180 mcg |
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Experimental: Arm C - Bulevirtide 10 mg/day
Bulevirtide 10 mg/day in combination with peginterferon alfa-2a for 48 weeks followed by Bulevirtide 10 mg/day for 48 weeks and additional 48 weeks follow up
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Drug: Bulevirtide
daily subcutaneus injections
Other Name: Myrcludex B Drug: Peginterferon Alfa-2a weekly subcutaneus injections at a dose 180 mcg |
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Experimental: Arm D - Bulevirtide 10 mg/day
Bulevirtide 10 mg/day for 96 weeks with additional 48 weeks follow up
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Drug: Bulevirtide
daily subcutaneus injections
Other Name: Myrcludex B |
Primary Outcome Measures :
- Sustained virological response 24 (SVR 24) defined as undetectable HDV RNA (HDV RNA <LLoD) at week 24 after the scheduled end of treatment (study week 120 for arms B, C and D) [ Time Frame: 24 weeks after the scheduled end of treatment ]Sustained virological response 24 (SVR 24) defined as undetectable HDV
Secondary Outcome Measures :
- Number of Participants with undetectable HDV RNA at week 48 (all arms), 96 (arms B, C and D) [ Time Frame: 48 weeks, 96 weeks ]Number of Participants with undetectable HDV RNA at week 48 (all arms), 96
- Number of Participants with combined sustained response after the scheduled end of treatment: undetectable HDV RNA or decrease by ≥ 2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization [ Time Frame: 24 weeks, 48 weeks ]Number of Participants with combined sustained response after the scheduled end of treatment: undetectable HDV RNA or decrease by ≥ 2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization
- Number of Participants with sustained virological response 48 (SVR 48) defined as undetectable HDV RNA at week 48 after the scheduled end of treatment [ Time Frame: 48 weeks ]Number of Participants with sustained virological response 48 (SVR 48)
- Number of Participants with change from baseline in liver stiffness as measured by elastography at week 48, 96, and 144 [ Time Frame: 48 weeks, 96 weeks, 144 weeks ]Number of Participants with change from baseline in liver stiffness as
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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:
- Provision of signed and dated informed consent form.
- Male or female, aged 18-65 years (inclusive).
- Positive serum hepatitis Delta virus (HDV) antibody results or polymerase chain reaction (PCR) results for serum/ plasma HDV 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 >2.8 mg/dL.
- Thyroid stimulating hormone (TSH) within normal ranges (including on medication for control of thyroid function)
- Negative urine pregnancy test for females of childbearing potential.
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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 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 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 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. Child-Pugh hepatic insufficiency score of 6 points is allowed. Only patients with compensated cirrhosis are allowed. Uncomplicated oesophageal varices allowed; Subjects with current bleeding or ligation, or history of bleeding or ligation within the last 2 years are excluded.
- Hepatitis С virus (HCV) or HIV coinfection. Subjects 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. [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.]
- 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.
- 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].
- Previous or unstable concurrent diseases or conditions that prevent subject's enrolment into the study.
- Patients 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 patients from participation in this trial.
- White blood cells (WBC) count < 3000 cells/mm3 (<1500 if African patients).
- Absolute neutrophil count < 1500 cells/mm3 (<1000 if African patients).
- Platelet count < 90,000 cells/mm3.
- 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. 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.
- 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.
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): NCT03852433
Contacts
| Contact: Yana Deloveri, MD | +74957265253 | deloveri@myr-pharma.com | |
| Contact: Alexander Alexandrov, MD | +491777168259 | alexandrov@myr-pharma.com |
Locations
Show 20 study locations
Sponsors and Collaborators
MYR GmbH
Hepatera Ltd.
Investigators
| Principal Investigator: | Pavel Bogomolov, MD | Moscow Regional Scientific and Research Clinical Institute |
| Responsible Party: | MYR GmbH |
| ClinicalTrials.gov Identifier: | NCT03852433 |
| Other Study ID Numbers: |
MYR 204 |
| First Posted: | February 25, 2019 Key Record Dates |
| Last Update Posted: | December 19, 2019 |
| Last Verified: | August 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | 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 Peginterferon alfa-2a Interferon-alpha Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs |