HIDIT II - PegIFN-alfa2a Plus Tenofovir in Chronic Delta Hepatitis

Hepatitis D Clinical Trial

— HIDIT-II  

Official title:

A Multicenter Randomised Study Comparing the Efficacy of PegIFN-alfa2a Plus Placebo vs. PegIFN-alfa2a Plus Tenofovir for the Treatment of Chronic Delta Hepatitis-The Hep-Net International Delta Hepatitis Interventional Trial II (HIDIT-II)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00932971
• Other study ID #: Hep-Net-HIDIT-II
• Secondary ID: EudraCT-No.: 200
• Status: Completed
• Phase: Phase 2
• First received: July 3, 2009
• Last updated: January 26, 2018
• Start date: June 2009
• Est. completion date: August 2, 2017

Study information

• Verified date: January 2018
• Source: HepNet Study House, German Liverfoundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, double blind study comparing the efficacy of pegylated interferon-alfa2a plus placebo versus pegylated interferon-alfa2a plus tenofovir for the treatment of chronic delta hepatitis. 70 Patients will be randomized 1:1 into the two groups. Treatment duration: 96 weeks. Follow-up: 24 weeks. Long-term-follow-up: until week 358.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: August 2, 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent.

• Age > 18 years.

• Positive HBsAg, for at least the prior 6 months, positive anti-HDV for at least 3 months and positive for HDV-RNA by PCR within the screening period.

• Elevated serum ALT = ULN but = 10X ULN as determined by two abnormal values taken > 1 month apart during the 12 months before the first dose of study drug with at least one of the determinations obtained = 35 days prior to the first dose.

• A liver biopsy obtained within the past 12 months demonstrating liver disease consistent with chronic hepatitis. Patients with cirrhosis on liver biopsy must also have a liver imaging investigation to rule out hepatic carcinoma.

• Negative urine or serum pregnancy test documented within the 24 hour period prior to the first dose of test drug.

• Additionally, all fertile males with partners of childbearing age and females should use two reliable forms of effective contraception (combined) throughout the entire period of the study (treatment and for 4 months after treatment completion)

• Creatinine clearance = 70 mL/min

Exclusion Criteria:

• Patients must not have received antiviral therapy for their chronic hepatitis D within the previous 6 months. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded.

• Positive test at screening for HAV-Ag-IgM, HCV-RNA or HCV-Ag or HIV-Ag.

• Serum concentrations of ceruloplasmin or alpha-1-antitrypsin consistent with an increased risk of metabolic liver disease.

• Evidence of decompensated liver disease (Childs B-C).

• History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia).

• Women with ongoing pregnancy or who are breast feeding.

• WBC count of < 3.000 cells/ mm3; neutrophil count < 1.500 cells/mm3or platelet count < 90.000 cells/mm3.

• Evidence of alcohol and/or drug abuse within one year of entry.

• Patients are excluded if any history of psychiatric disease, especially depression, or of suicidal attempts is evident.

• History of immunologically mediated disease.

• History or other evidence of decompensated liver disease.

• History or other evidence of chronic pulmonary disease associated with functional limitation.

• History of severe cardiac disease

• Evidence of an active or suspected cancer or a history of malignancy where there is a risk of cancer to recur.

• History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) = 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.

• History of any organ transplantation with an existing functional graft

• History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.

• History or evidence of severe retinopathy or clinically relevant ophthalmological disorder.

• Inability or unwillingness to provide informed consent or abide by the requirements of the study.

• History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.

• Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months.

• History or evidence for any intolerance or hypersensitivity to pegylated interferon-alfa-2a, tenofovir or other substances part of the study medication.

• Current participation in any other investigational trial and participation in another investigational trial within 3 months before the trial begins.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis D
• Hepatitis D, Chronic

Intervention

Drug:
• PEG-IFN alfa-2a, Tenofovir
Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Tenofovir disoproxilfumarat, 245mg, once daily, orally
• PEG-IFN alfa-2a, placebo
Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Placebo, once daily, orally

Locations

Country	Name	City	State
Germany	Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie	Berlin
Germany	Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I	Bonn
Germany	Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie	Düsseldorf
Germany	Klinikum der J.W. Goethe-Universität	Frankfurt
Germany	Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin	Hamburg
Germany	Medizinische Hochschule Hannover, Zentrum Innere Medizin	Hannover
Germany	Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV	Heidelberg
Greece	Athens University School of Medicine, Hippokration General Hospital	Athens
Romania	Institutul de Boli Infectioase "Prof. Dr. Matei Bals"	Bucharest
Romania	Spitalul Clinic de Boli Infectioase si	Timisoara

Sponsors (4)

Lead Sponsor	Collaborator
HepNet Study House, German Liverfoundation	Gilead Sciences, Hannover Clinical Trial Center GmbH, Hoffmann-La Roche

Countries where clinical trial is conducted

Germany,  Greece,  Romania, 

References & Publications (3)

Heidrich B, Deterding K, Tillmann HL, Raupach R, Manns MP, Wedemeyer H. Virological and clinical characteristics of delta hepatitis in Central Europe. J Viral Hepat. 2009 Dec;16(12):883-94. doi: 10.1111/j.1365-2893.2009.01144.x. Epub 2009 Jun 28. — View Citation

Heidrich B, Yurdaydin C, Kabaçam G, Ratsch BA, Zachou K, Bremer B, Dalekos GN, Erhardt A, Tabak F, Yalcin K, Gürel S, Zeuzem S, Cornberg M, Bock CT, Manns MP, Wedemeyer H; HIDIT-1 Study Group. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology. 2014 Jul;60(1):87-97. doi: 10.1002/hep.27102. — View Citation

Wedemeyer H, Yurdaydìn C, Dalekos GN, Erhardt A, Çakaloglu Y, Degertekin H, Gürel S, Zeuzem S, Zachou K, Bozkaya H, Koch A, Bock T, Dienes HP, Manns MP; HIDIT Study Group. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011 Jan 27;364(4):322-31. doi: 10.1056/NEJMoa0912696. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Negativation of HDV-RNA at the end of therapy		week 96
Secondary	Negativation of HDV-RNA at week 48 of treatment		week 48
Secondary	Negativation of HDV-RNA 24 weeks after the end of treatment		week 120
Secondary	Normalization of ALT levels at the end of treatment and at the end of follow-up		week 96 and week 356
Secondary	HDV-RNA-levels over time		up to week 356
Secondary	Suppression of HBV-DNA below 6 IU/ml using the Cobas TaqMan assay at treatment weeks 48 and 96 and 24 weeks after treatment		week 48, week 96, week 120
Secondary	Liver histology at end of treatment (Ishak score for inflammation and fibrosis)		week 96
Secondary	Quantitative HBsAg levels over time. Loss of HBsAg and development of anti-HBs antibodies, intrahepatic cccDNA and HBV-DNA levels over time		up to week 356
Secondary	HBV- and HDV-virus-specific T cell responses during therapy and after 24 weeks of follow up if virological and biochemical efficacy has been shown		up week 120
Secondary	Virological long-term outcome		1, 2, 3, 4 and 5 years after the end of treatment
Secondary	Clinical long-term outcome		1, 2, 3, 4 and 5 years after the end of treatment
Secondary	Quality of Life		up to week 356

External Links

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