CHRONIC HEPATITIS C MedDRA version: 20.0 Level: PT Classification code 10019744 Term: Hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: PEGASYS - 180MCG-SOLUZ. INIETTABILE-USO SOTTOCUT.-PENNA PRERIEMPITA-0.5 ML (360MCG/ML) 1 PENNA PRERIEMPITA
Product Name: PEGINTERFERONE ALFA-2A
Product Code: N.A.
Pharmaceutical Form: Solu
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA DI PARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, age = 18 years 2. Evidence of genotype 1 HCV infection (molecular assay) 3. Quantifiable plasma HCV RNA 4. Documented mild or moderate liver fibrosis (Metavir F0-F3 or Ishak 0-4) assessed by liver biopsy in the past 24 months or by FibroScan™/Elastography (=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Infection or coinfection with HCV of another genotype than genotype 1 2. Contraindication to the administration of Peg-IFN-alfa or RBV, or medical history or laboratory values that preclude treatment with Peg-IFN-alfa or RBV according to the respective local prescribing information 3. Prior exposure to anti-HCV treatment, including any approved or investigational DAA therapy 4. Signs or symptoms of HCC. Serum alpha-fetoprotein (AFP) level and ultrasonography should be available at screening for all subjects (both tests should have been done a maximum of 4 months before the screening visit). 5. History of decompensated liver disease: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, and/or any of the following screening laboratory results: a. International Normalized Ratio (INR) of =1.5 b. Serum albumin 1.8 times the upper limit of the laboratory normal range, unless isolated or in subjects with Gilbert’s Syndrome. 6. Coinfection with active hepatitis B or HIV 7. Any of the following laboratory abnormalities (assessed at local laboratory) as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS): Absolute neutrophil count (ANC) 10% of the body, where the palm of one hand equals 1%, or if the hands and feet are affected], rheumatoid arthritis requiring more than intermittent nonsteroidal anti inflammatory medications for management); in case of patients with both autoimmune and viral hepatitis, the sponsor will make the decision about enrollment. 14. Clinical evidence of chronic pulmonary disease associated with functional impairment 15. History of uncontrolled severe seizure disorders 16. Has a history or other evidence of a clinically relevant ophthalmologic disorder due to diabetes mellitus or hypertension or history or other evidence of severe retinopathy (eg, cytomegalovirus, macular degeneration) 17. Has a history of major organ transplantation with an existing functional graft with the exception of corneal transplants and skin grafts 18. Pregnant or breast-feeding woman 19. eGFR <30 ml/min/1.73 mq2 or ESRD 20. Use of any medications listed below, within 2 weeks prior to study drug administration: amiodarone, rosuvastatine, proton pump inhibitors at a dosage of omeprazole higher than 20 mg, metotrexate, sulfasalazin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether antiviral therapy with last generation DAA is associated with restoration of HCV-specific T cell responses and whether level of restoration is negatively influenced by simultaneous administration of IFN-alfa;Secondary Objective: To assess: - whether early changes in NK cell phenotype can be detected in DAA treated patients in the search of putative predictors of accelerated response or non response to therapy to be validated in future extended studies; - whether HCV genetic heterogeneity at baseline may influence the anti-HCV specific immune response, and/or wheter the emergence under treatment of HCV mutants resistant to therapy may impair anti-viral T cell responses. ;Primary end point(s): - the percentage of patients showing improvement of CD4- and CD8-mediated HCV-specific T cell responses ex vivo and following in vitro expansion (cytokine production by intracellular cytokine staining and cytotoxicity by CD107 degranulation in flow cytometry) during treatment and follow-up compared to pre-treatment responses and the magnitude of improvement of the anti-viral T cell response; - the difference in functional T cell restoration between patients receiving DAA with or without ¿-inteferon by comparing levels of T cell responses during treatment and follow-up in the two groups of patients; - the time required for restoration of individual anti-viral T cell functions (cytotoxicity, IL2, TNF-alfa and IFN-gamma production) from start of therapy in each group of patients to assess which functions are more deeply exhausted and more difficult to be restored. ;Timepoint(s) of evaluation of this end point: end of the follow-up period of all enrolled patients | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - the identification of NK cell phenotypic parameters showing changes in their expression detected by flow cytometry during therapy compared to pre-treatment time points; - the correlation between baseline HCV variants carrying mutations potentially affecting response to therapy or contained within potential T cell epitopic regions and intensity/specificity of HCV-specific T cell responses; - the effect of HCV mutants potentially resistant to therapy emerging during treatment on HCV-specific T cell responses. ;Timepoint(s) of evaluation of this end point: end of the follow-up period of all enrolled patients | — |
Countries
Italy
Contacts
Public ContactSEGRETERIA COMITATO ETICO
AZIENDA OSPEDALIERO-UNIVERSITARIA DI PARMA
Outcome results
None listed