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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Hepatitis D

Intervention / Treatment
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* Drug: PEG-IFN alfa-2a, Tenofovir
* Drug: PEG-IFN alfa-2a, placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PEG-IFN alfa-2a plus placebo<br>Pegylated interferon alfa-2a 180 µg once weekly (QW) subcutaneous (sc) plus placebo once daily, orally | Drug: PEG-IFN alfa-2a, placebo<br>* Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Placebo, once daily, orally<br>* Other names: Pegasys;|
| Active Comparator: PEG-IFN alfa-2a plus Tenofovir<br>Pegylated interferon alfa-2a 180 µg once weekly (QW) subcutaneous (sc) plus Tenofovir disoproxilfumarat 245mg once daily, orally | Drug: PEG-IFN alfa-2a, Tenofovir<br>* Pegylated interferon alfa-2a, 180µg once weekly, subcutaneously; Tenofovir disoproxilfumarat, 245mg, once daily, orally<br>* Other names: Viread;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negativation of HDV-RNA at the end of therapy |  | week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negativation of HDV-RNA at week 48 of treatment |  | week 48 | 
| Negativation of HDV-RNA 24 weeks after the end of treatment |  | week 120 | 
| Normalization of ALT levels at the end of treatment and at the end of follow-up |  | week 96 and week 356 | 
| HDV-RNA-levels over time |  | up to week 356 | 
| 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 | 
| Liver histology at end of treatment (Ishak score for inflammation and fibrosis) |  | week 96 | 
| 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 | 
| 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 | 
| Virological long-term outcome |  | 1, 2, 3, 4 and 5 years after the end of treatment | 
| Clinical long-term outcome |  | 1, 2, 3, 4 and 5 years after the end of treatment | 
| Quality of Life |  | up to week 356 |