Myrcludex B Plus Pegylated Interferon-alpha-2a in Patients With HBeAg Negative HBV/HDV Co-infection

NCT02637999 | Completed Phase 1 Results

• 1 other identifier: MYR 201 (HDV)
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Randomized open-label substudy of daily Myrcludex B (MXB) plus pegylated interferon-alpha-2a (PEG-INF-a) in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B virus (HBV) co-infected with hepatitis delta virus (HDV).

Conditions

Chronic Hepatitis D Infection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 12 of Therapy

  HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 12 compared to baseline (including the patient with negative baseline level)

  Baseline and 12 weeks

Secondary Outcomes (8)

• Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 24 of Therapy

  Baseline and 24 weeks

• Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 24 of Therapy

  Baseline and 24 weeks

• Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 12 of Therapy

  Baseline and 12 weeks

• Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 12 of Therapy

  Baseline and 12 weeks

• Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 24 of Therapy

  Baseline and 24 weeks

Study Arms (3)

MXB then PEG IFN

EXPERIMENTAL

Myrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL weekly for 48 weeks

Drug: PEG IFN alfa-2a; Drug: Myrcludex B

MXB + PEG IFN then PEG IFN

EXPERIMENTAL

Myrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL weekly for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL weekly for 24 weeks

Drug: PEG IFN alfa-2a; Drug: Myrcludex B

PEG IFN

ACTIVE COMPARATOR

PEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks

Drug: PEG IFN alfa-2a

Interventions

PEG IFN alfa-2a DRUG

Also known as: Pegasys

MXB + PEG IFN then PEG IFN; MXB then PEG IFN; PEG IFN

Myrcludex B DRUG

Also known as: Myrcludex

MXB + PEG IFN then PEG IFN; MXB then PEG IFN

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic hepatitis B defined by the presence of HBsAg for at least 6 months prior to screening period. Co-infection with hepatitis D virus defined as positive anti-HDV antibodies for at least 3 months and positive for HDV-RNA within the screening period.
• Liver biopsy performed within one year prior to screening or during screening period.
• HBeAg negative
• All women of childbearing potential must have a negative urine pregnancy test prior to enrolment.
• Women must:
• Be menopausal for at least 2 years, or
• Be surgically sterile (total hysterectomy or bilateral ovariectomy or bilateral tubal ligation/clips or otherwise be incapable of pregnancy), or
• Not be heterosexually active during the study, or
• Agree to use a highly effective method of birth control (double barrier method or combination of barrier method with hormonal or intrauterine device) during the study and for 3 month after the last dosing of the investigational medicinal product.
• Men must agree to use a highly effective method of birth control (double barrier methods or combination of barrier method with hormonal or intrauterine device in their women-partner) and not to donate a sperm during the study and for 3 month after the last dosing of the investigational medicinal product.
• An understanding, ability and willingness to fully comply with study procedures and restrictions.
• An ability to provide the written informed consent to participate in the study

You may not qualify if:

• Decompensated liver disease (Child-Pugh-Score \>6).
• Co-infected with hepatitis C virus (HCV), or HIV.
• Patients with presence of anti-HCV antibody and negative HCV RNA in two separate occasions within 12 months prior to screening could be enrolled into the study after sponsor written permission.
• ALT \> 6 ULN.
• Creatinine clearance \< 60 mL/min.
• Total bilirubin \> 2 mg/dL.
• Confirmed contraindication for treatment with PEG-INF-a.
• History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein (AFP) levels. In patients with such findings, HCC will be ruled-out prior to screening for the present study.
• 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, e.g. congestive heart failure or other severe cardiopulmonary disease). Patients with Gilbert's syndrome and Dubin-Johnson syndrome, two benign disorders associated with low-grade hyperbilirubinemia can be enrolled into the trial.
• History of clinically evident pancreatitis.
• History of alcohol or drug abuse within the preceding two years. For the purposes of the present study, alcohol abuse is arbitrarily defined as frequent consumption of alcoholic beverages with an average daily intake of more than 40 g of ethanol.
• Participation in another study with an investigational drug within less than one month prior to this study or simultaneously to this study.
• Patients who are unable or unwilling to follow the protocol requirements.
• Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator.
• Patients with limited mental capacity to the extent that she/he cannot provide informed consent or information regarding adverse events of the study drug.

Sponsors & Collaborators

• Hepatera Ltd.: lead

Related Publications (6)

• Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004 Mar;11(2):97-107. doi: 10.1046/j.1365-2893.2003.00487.x.

  PMID: 14996343 BACKGROUND

• Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13;1:e00049. doi: 10.7554/eLife.00049.

  PMID: 23150796 BACKGROUND

• Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 2003 Apr;83(2):633-71. doi: 10.1152/physrev.00027.2002.

  PMID: 12663868 BACKGROUND

• Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R, Ronchi G, Colombo M. A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009 May;136(5):1629-38. doi: 10.1053/j.gastro.2009.01.052. Epub 2009 Jan 29.

  PMID: 19208358 BACKGROUND

• Cornberg M, Protzer U, Dollinger MM, Petersen J, Wedemeyer H, Berg T, Jilg W, Erhardt A, Wirth S, Schirmacher P, Fleig WE, Manns MP. Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: the German guidelines for the management of HBV infection. Z Gastroenterol. 2007 Dec;45(12):1281-328. doi: 10.1055/s-2007-963714. No abstract available.

  PMID: 18080231 BACKGROUND

• Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T, Alexandrov A, Haag M, Schwab M, Urban S, Haefeli WE. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016 Sep;65(3):483-9. doi: 10.1016/j.jhep.2016.04.013. Epub 2016 Apr 27.

  PMID: 27132172 BACKGROUND

MeSH Terms

Interventions

peginterferon alfa-2a; myrcludex-B

Results Point of Contact

• Title: Dr. med. Alexander Alexandrov
• Organization: MYR GmbH

alexandrov@myr-pharma.com

+491777168259

Study Officials

• Pavel Bogomolov, PhD

  LLC "Clinical Hospital of Tsentrosoyuz"

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 22, 2015
• Study Start: February 13, 2014
• Primary Completion: January 21, 2016
• Study Completion: January 21, 2016
• Last Updated: April 13, 2018
• Results First Posted: April 13, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share