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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Hannover Clinical Trial Center GmbH
Hoffmann-La Roche
Gilead Sciences
Information provided by (Responsible Party):
HepNet Study House, German Liverfoundation
ClinicalTrials.gov Identifier:
NCT00932971
First received: July 3, 2009
Last updated: June 13, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis D
Drug: PEG-IFN alfa-2a, Tenofovir
Drug: PEG-IFN alfa-2a, placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by HepNet Study House, German Liverfoundation:

Primary Outcome Measures:
  • Negativation of HDV-RNA at the end of therapy [ Time Frame: week 96 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Negativation of HDV-RNA at week 48 of treatment [ Time Frame: week 48 ] [ Designated as safety issue: No ]
  • Negativation of HDV-RNA 24 weeks after the end of treatment [ Time Frame: week 120 ] [ Designated as safety issue: No ]
  • Normalization of ALT levels at the end of treatment and at the end of follow-up [ Time Frame: week 96 and week 356 ] [ Designated as safety issue: No ]
  • HDV-RNA-levels over time [ Time Frame: up to week 356 ] [ Designated as safety issue: No ]
  • Suppression of HBV-DNA below 6 IU/ml using the Cobas TaqMan assay at treatment weeks 48 and 96 and 24 weeks after treatment [ Time Frame: week 48, week 96, week 120 ] [ Designated as safety issue: No ]
  • Liver histology at end of treatment (Ishak score for inflammation and fibrosis) [ Time Frame: week 96 ] [ Designated as safety issue: No ]
  • Quantitative HBsAg levels over time. Loss of HBsAg and development of anti-HBs antibodies, intrahepatic cccDNA and HBV-DNA levels over time [ Time Frame: up to week 356 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: up week 120 ] [ Designated as safety issue: No ]
  • Virological long-term outcome [ Time Frame: 1, 2, 3, 4 and 5 years after the end of treatment ] [ Designated as safety issue: No ]
  • Clinical long-term outcome [ Time Frame: 1, 2, 3, 4 and 5 years after the end of treatment ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: up to week 356 ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: June 2009
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: PEG-IFN alfa-2a plus placebo
Pegylated interferon alfa-2a 180 µg once weekly (QW) subcutaneous (sc) plus placebo once daily, orally
Drug: PEG-IFN alfa-2a, placebo
Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Placebo, once daily, orally
Other Name: Pegasys
Active Comparator: PEG-IFN alfa-2a plus Tenofovir
Pegylated interferon alfa-2a 180 µg once weekly (QW) subcutaneous (sc) plus Tenofovir disoproxilfumarat 245mg once daily, orally
Drug: PEG-IFN alfa-2a, Tenofovir
Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Tenofovir disoproxilfumarat, 245mg, once daily, orally
Other Names:
  • Pegasys
  • Viread

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00932971

Locations
Germany
Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie
Berlin, Germany, 13353
Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I
Bonn, Germany, 53105
Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie
Düsseldorf, Germany, 40225
Klinikum der J.W. Goethe-Universität
Frankfurt, Germany, 60590
Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin
Hamburg, Germany, 20246
Medizinische Hochschule Hannover, Zentrum Innere Medizin
Hannover, Germany, 30625
Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV
Heidelberg, Germany, 69120
Universitätsklinikum Leipzig
Leipzig, Germany, 04103
Klinikum Großhadern, Med. Klinik 2
München, Germany, 81366
Med. Poliklinik der Universität Würzburg
Würzburg, Germany, 97080
Greece
Athens University School of Medicine, Hippokration General Hospital
Athens, Greece, 11527
Romania
Institutul de Boli Infectioase "Prof. Dr. Matei Bals"
Bucharest, Romania, 021105
Spitalul Clinic de Boli Infectioase si
Timisoara, Romania, 300312
Sponsors and Collaborators
HepNet Study House, German Liverfoundation
Hannover Clinical Trial Center GmbH
Hoffmann-La Roche
Gilead Sciences
Investigators
Study Director: Michael P. Manns, Prof. Dr. Hannover Medical School
  More Information

Additional Information:
Publications:
Responsible Party: HepNet Study House, German Liverfoundation
ClinicalTrials.gov Identifier: NCT00932971     History of Changes
Other Study ID Numbers: Hep-Net-HIDIT-II, EudraCT-No.: 2008-005560-13
Study First Received: July 3, 2009
Last Updated: June 13, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis D
Hepatitis D, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepatitis, Chronic
Interferon-alpha
Tenofovir
Tenofovir disoproxil
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 30, 2014