Chronic Hepatitis D Infection Clinical Trial
Official title:
Randomized Open-label Substudy of Daily Myrcludex B Plus Pegylated Interferon-alpha-2a in Patients With HBeAg Negative Chronic Hepatitis B Co-infected With Hepatitis Delta
Verified date | April 2018 |
Source | Hepatera Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 24 |
Est. completion date | January 21, 2016 |
Est. primary completion date | January 21, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - 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: 1. Be menopausal for at least 2 years, or 2. Be surgically sterile (total hysterectomy or bilateral ovariectomy or bilateral tubal ligation/clips or otherwise be incapable of pregnancy), or 3. Not be heterosexually active during the study, or 4. 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 Exclusion Criteria: - 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. - Clinically significant renal, respiratory or cardiovascular disease. - Pregnancy and lactation. - Patients who have previously participated in this study. |
Country | Name | City | State |
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n/a |
Lead Sponsor | Collaborator |
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Hepatera Ltd. |
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. — View Citation
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. — View Citation
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. Review. — View Citation
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. — View Citation
Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 2003 Apr;83(2):633-71. Review. — View Citation
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. Erratum in: Elife. 2014;3:e05570. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 24 of Therapy | HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 24 compared to baseline (including the patient with negative baseline level) | Baseline and 24 weeks | |
Secondary | Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 24 of Therapy | HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level) | Baseline and 24 weeks | |
Secondary | Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 12 of Therapy | HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level) | Baseline and 12 weeks | |
Secondary | Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 12 of Therapy | HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level) | Baseline and 12 weeks | |
Secondary | Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 24 of Therapy | HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level) | Baseline and 24 weeks | |
Secondary | Number of Participants With Biochemical Response at Week 12 of Therapy | Biochemical response was defined as normalization of ALT level as compared to baseline. | Baseline and 12 weeks | |
Secondary | Number of Participants With Biochemical Response at Week 24 of Therapy | Biochemical response was defined as normalization of ALT level as compared to baseline. | Baseline and 24 weeks | |
Secondary | Number of Participants With Covalently Closed Circular Deoxyribonucleic Acid (cccDNA) Response at Week 72 of Therapy | Virological cccDNA response was defined as reduction of intrahepatic cccDNA by 0.5 log in comparison to baseline at the end of follow up. | Baseline and 72 weeks for arm A and 48 weeks for arms B and C |
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