To compare the virological efficacy (HDV-RNA) and safety of 96 weeks of therapy with pegylated interferon-alfa-2a plus tenovofir to 96 weeks of therapy with pegylated interferon-alfa-2a plus placebo for the treatment with chronic delta hepatits virus. MedDRA version: 15.1 Level: LLT Classification code 10047455 Term: Viral hepatitis B without mention of hepatic coma, with hepatitis delta System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Viread
Pharmaceutical Form: Tablet
INN or Proposed INN: TENOFOVIR
CAS Number: 147127206
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 245-
Pharmaceuti
Sponsors
Medizinische Hochschule Hannover
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years; 2. 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. 3. Elevated serum ALT >= ULN but 1 month apart during the 12 months before the first dose of study drug with at least one of the determinations obtained = 70 mL/min by the following formula: ((140-age in years) (body weight (kg)):((72) (serum creatinine [mg/dl])) [Note: multiply estimated rate by 0.85 for women] 7. written informent consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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. Exception: patients who have had a limited (100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. 22. Reassessments: If a patient fails to meet the above inclusion /e
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the virological efficacy (HDV-RNA) and safety of 96 weeks of therapy with PEG-IFN-2a plus tenofovir to 96 weeks of therapy with PEG-IFN-2a plus placebo for the treatment of patients with chronic delta hepatitis virus.;Secondary Objective: To explore the effects of the two treatment regimens on HDV-RNA-levels, HBsAg levels, HBV DNA, biochemical disease activity and liver histology. Virus-specific T cell responses during therapy and after 24 weeks of the treament will be analysed on stored PBMC samples if virological and biochemical efficacy has been shown. In addition, the objective of this study is to determine the virological and clinical long-term outcome of treatment of delta hepatitis. ;Primary end point(s): Primary endpoint: • Negativation of HDV-RNA at the end of therapy ;Timepoint(s) of evaluation of this end point: Week 96 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Negativation of HDV-RNA 2. Negativation of HDV-RNA 3. Normalization of ALT levels 4. HDV-RNA-levels 5. Quantitative HBsAg levels over time and loss of HBsAg and development of anti-HBs antibodies. 6. Suppression of HBV-DNA below 6 IU/ml using the Cobas TaqMan assay 7. Liver histology: Changes in Ishak scores for inflammation and fibrosis 8. Intrahepatic HBVcccDNA in patients with samples available 9. HBV- and HDV-virus-specific T cell responses 10. Quality of life (SF36 questionnaire) 11. Virological long-term outcome (HBsAg, HBeAg, anti-HBs, anti-HBe, HBV-DNA, HDV-RNA) 12. Clinical long-term outcome (normalization of ALT, development of hepatocellular carcinoma, hepatic decompensation, liver transplantation, death);Timepoint(s) of evaluation of this end point: 1. Week 48 of treatment 2. 24 weeks after the end of treatment 3. End of therapy and at the end of follow-up 4. Over time of study 5. Over time of study 6. At treatment weeks 48 and 96 and 24 weeks after treatment 7. End of treatment as compared to pre-treatment biopsies at and after treatment 8. Only when available 9. During therapy and after 24 weeks of follow up if virological and biochemical efficacy has been shown, including measurements of serum cytokines and chemokines 10. Week 24, 48 and 96 11. 1, 2, 3, 4 and 5 years after the end of treatment 12. 1, 2, 3, 4 and 5 years after the end of treatment | — |
Countries
Germany, Greece
Contacts
Public ContactMichael Manns
Medizinische Hochschule Hannover
Outcome results
None listed