HIDIT II - PegIFN-alfa2a Plus Tenofovir in Chronic Delta Hepatitis
Information source: HepNet Study House, German Liverfoundation
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis D
Intervention: PEG-IFN alfa-2a, Tenofovir (Drug); PEG-IFN alfa-2a, placebo (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: HepNet Study House, German Liverfoundation Official(s) and/or principal investigator(s): Michael P. Manns, Prof. Dr., Study Director, Affiliation: Hannover Medical School
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.
Clinical Details
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)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Negativation of HDV-RNA at the end of therapy
Secondary outcome: Negativation of HDV-RNA at week 48 of treatmentNegativation of HDV-RNA 24 weeks after the end of treatment Normalization of ALT levels at the end of treatment and at the end of follow-up HDV-RNA-levels over time Suppression of HBV-DNA below 6 IU/ml using the Cobas TaqMan assay at treatment weeks 48 and 96 and 24 weeks after treatment Liver histology at end of treatment (Ishak score for inflammation and fibrosis) Quantitative HBsAg levels over time. Loss of HBsAg and development of anti-HBs antibodies, intrahepatic cccDNA and HBV-DNA levels over time 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 Virological long-term outcome Clinical long-term outcome Quality of Life
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie, Berlin 13353, Germany
Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I, Bonn 53105, Germany
Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Düsseldorf 40225, Germany
Klinikum der J.W. Goethe-Universität, Frankfurt 60590, Germany
Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin, Hamburg 20246, Germany
Medizinische Hochschule Hannover, Zentrum Innere Medizin, Hannover 30625, Germany
Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV, Heidelberg 69120, Germany
Universitätsklinikum Leipzig, Leipzig 04103, Germany
Klinikum Großhadern, Med. Klinik 2, München 81366, Germany
Med. Poliklinik der Universität Würzburg, Würzburg 97080, Germany
Athens University School of Medicine, Hippokration General Hospital, Athens 11527, Greece
Institutul de Boli Infectioase "Prof. Dr. Matei Bals", Bucharest 021105, Romania
Spitalul Clinic de Boli Infectioase si, Timisoara 300312, Romania
Additional Information
Related publications: 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. Wedemeyer H, Yurdaydìn C, Dalekos GN, Erhardt A, Çakaloğlu Y, Değertekin 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.
Starting date: June 2009
Last updated: December 3, 2014
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