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A Multicenter, Open-label, Randomized Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination With Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients With Chronic Hepatitis D

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ClinicalTrials.gov Identifier: NCT03546621
Recruitment Status : Completed
First Posted : June 5, 2018
Last Update Posted : June 5, 2018
Sponsor:
Collaborator:
Data Matrix Solutions
Information provided by (Responsible Party):
Hepatera Ltd.

Brief Summary:
This is a multicenter, open-label, randomized clinical trial to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination with Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients with Chronic Hepatitis D

Condition or disease Intervention/treatment Phase
Chronic Hepatitis D Infection With Hepatitis B Drug: Myrcludex B Drug: Myrcludex-B Drug: Tenofovir Phase 2

Detailed Description:

This is a multicenter, open-label, randomised, phase II study.

The study will be conducted in Russia and Germany. The study is designed to evaluate the benefit of 3 MXB doses versus observation in patients on background therapy with tenofovir, suffering from hepatitis delta with very limited therapeutic options; the patients will be randomized 1:1:1:1 into 3 treatment arms and an observation arm. Patients with compensated cirrhosis at screening will be stratified to allow similar distribution into each treatment arm. If patients were not receiving treatment with nucleoside/nucelotide analogue, the comparator/background drug will be initiated after the eligibility confirmation, for 12 weeks prior to randomization visit; patients who previously received tenofovir will continue the dosing; patients on different nucleoside/nucleotide analogue will be switched to tenofovir. Observation is considered an adequate control group, as daily placebo injections for 24 weeks are regarded not feasible and ethically questionable.

It is planned to screen 200 patients, and 120 patients will be randomised into four treatment arms in the 1:1:1:1 ratio.

  • Arm A (30 patients): Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
  • Arm B (30 patients): Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
  • Arm C (30 patients): Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
  • Arm D (30 patients): tenofovir treatment for 48 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 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 Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination With Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients With Chronic Hepatitis D
Actual Study Start Date : February 16, 2016
Actual Primary Completion Date : January 31, 2018
Actual Study Completion Date : January 31, 2018


Arm Intervention/treatment
Experimental: Arm A
Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
Drug: Myrcludex B
2 mg, once daily, subcutaneously

Drug: Tenofovir
tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Other Name: Viread

Experimental: Arm B
Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
Drug: Myrcludex-B
5 mg, once daily, subcutaneously

Drug: Tenofovir
tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Other Name: Viread

Experimental: Arm C
Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.
Drug: Myrcludex-B
10 mg, once daily, subcutaneously

Drug: Tenofovir
tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Other Name: Viread

Active Comparator: Arm D
tenofovir treatment for 48 weeks
Drug: Tenofovir
tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Other Name: Viread




Primary Outcome Measures :
  1. HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24 [ Time Frame: 24 weeks ]
    HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24


Secondary Outcome Measures :
  1. Durability of HDV RNA response to 24 weeks post treatment [ Time Frame: 24 weeks ]
  2. Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24 [ Time Frame: 24 weeks ]
  3. Changes in ALT values at Week 24 and Week 48 compared to baseline [ Time Frame: 24 and 48 weeks ]
  4. Lack of fibrosis progression based on transient elastometry (Fibroscan) at Week 24 compared to baseline. [ Time Frame: 24 weeks ]
  5. Changes (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline [ Time Frame: 24 and 48 weeks ]
  6. Changes in HBsAg (decreased levels, disappearance of HBsAg, antibodies to HBsAg) at Week 24 and Week 48 compared to baseline. [ Time Frame: 24 and 48 weeks ]
  7. Change in HBV DNA levels at Week 24 and Week 48 compared to baseline [ Time Frame: 24 and 48 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. Age from 18 to 65 years inclusively at the time of signing Informed Consent Form.
  2. Positive serum HBsAg for at least 6 months before Screening.
  3. Positive serum anti-HDV antibody for at least 6 months before screening.
  4. Positive PCR results for serum HDV RNA at Screening.
  5. Patients with liver cirrhosis, irrespective of previous interferon treatment .
  6. Patients without liver cirrhosis, who failed prior interferon treatment or for whom, in the opinion of the Investigator, such treatment is currently contraindicated (including history of interferon intolerance) .
  7. Alanine aminotransferase level >1 x ULN, but less than 10 x ULN.
  8. Previous nucleotide/nucleoside analogue treatment within at least 12 weeks prior to the planned start of study treatment or subject's willingness to take tenofovir for at least 12 weeks prior to the planned start of study treatment.
  9. Negative urine pregnancy test for females of childbearing potential.
  10. 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 throughout the study and for 3 months after the last dose of the study medication.
  11. Male and female subjects must agree to use a highly effective contraception throughout the study and for 3 months after the last dose of the study medication.
  12. Male subjects must agree not to donate sperm throughout the study and for 3 months after the last dose of the study medication.

Exclusion Criteria:

  1. Child-Pugh score of B-C or over 6 points.
  2. HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative.
  3. Creatinine clearance <60 mL/min.
  4. Total bilirubin ≥ 2mg/dL. Patients with higher total bilirubin values may be included after the consultation with the Study`s Medical Monitor, if such elevation can be clearly attributed to Gilbert's syndrome associated with low-grade hyperbilirubinemia.
  5. Any previous or current malignant neoplasms, including hepatic carcinoma.

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): NCT03546621


Locations
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Germany
Ifi-Institut für interdisziplinäre Medizin an der Asklepios Klinik St. Georg
Hamburg, Germany
Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie
Hamburg, Germany
Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
Hannover, Germany
UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie
Heidelberg, Germany
Russian Federation
State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare
Chelyabinsk, Russian Federation
State Autonomous Healthcare Institution "Republican Clinical Infectious Diseases Hospital named after Prof. A.F. Agafonov "(SAHI RCID)
Kazan, 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
LLC "Clinic of Modern Medicine"
Moscow, Russian Federation
Moscow Regional Research Clinical Institute n.a. M.F. Vladimirskiy
Moscow, Russian Federation
State Budget Health Institution of Moscow "Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department"
Moscow, Russian Federation
State Budgetary Healthcare Institution "Moscow Clinical Scientific and Practical Center of the Department of Public Health of Moscow"
Moscow, Russian Federation
State Budgetary Educational Institution of Higher Professional Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
Novosibirsk, Russian Federation
Medical Company "Hepatolog"
Samara, Russian Federation
Stavropol Regional Clinical Hospital
Stavropol', Russian Federation
State Budgetary institution of the Republic of Sakha (Yakutia) "Yakutsk Clinical Hospital"
Yakutsk, Russian Federation
Sponsors and Collaborators
Hepatera Ltd.
Data Matrix Solutions

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Responsible Party: Hepatera Ltd.
ClinicalTrials.gov Identifier: NCT03546621     History of Changes
Other Study ID Numbers: MYR 202
First Posted: June 5, 2018    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hepatera Ltd.:
Hepatitis D
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis D
Hepatitis D, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents