| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic hepatitis C virus infection. |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008912 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate the antiviral efficacy (sustained virologic response [SVR]; defined as undetectable HCV RNA 24 weeks following treatment cessation) of 16 and 24 weeks of response guided duration of therapy with GS-9190, GS-9256, ribavirin (RBV), and peginterferon alfa 2a (PEG). |
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| E.2.2 | Secondary objectives of the trial |
| . To evaluate the antiviral efficacy of 24 weeks of therapy with GS-9256, PEG and RBV • To evaluate the safety and tolerability of therapy in each treatment arm. • To evaluate the emergence of viral resistance following initiation of therapy with GS 9190 and GS-9256. • To characterize the viral dynamics and steady state pharmacokinetics of GS 9190 and GS 9256 when administered in combination with PEG and RBV. Exploratory objectives of this study include the following: • Assess genetic variation in the human IL28B gene as a predictor of virologic response in each treatment arm. • Through genetic discovery research (i.e., pharmacogenomics) in subjects who provide their additional and specific consent: to identify or validate genetic markers that may be predictive of the natural history of HCV disease, the virologic response to therapy, and the tolerability of drugs used in HCV therapeutics. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:Amend. 1 Data:2010/08/18 Titolo:Sottostudio farmacocinetico e della dinamica virale Obiettivi:Circa 80 soggetti (40 soggetti del braccio 1 e 20 soggetti rispettivamente dei bracci 2 e 3) saranno arruolati nei centri di studio selezionati per partecipare a un sottostudio farmacocinetico (PK) e della dinamica virale. L’arruolamento dei soggetti nel sottostudio PK/dinamica virale sara` gestito in modo tale che 20 soggetti nella coorte del braccio 1 e 10 soggetti rispettivamente nelle coorti del braccio 2 e del braccio 3 avranno il genotipo IL28B CC; i restanti soggetti arruolati avranno il genotipo IL28B CT oppure il TT. I campioni plasmatici per la valutazione HCV RNA e un campione plasmatico da archiviare saranno prelevati a 4, 6 e 8 ore dalla somministrazione della dose iniziale in giornata 1. I soggetti ritorneranno per un prelievo di HCV RNA plasmatico e di un campione per la conservazione circa 24 ore (giornata 2) e 48 ore (giornata 3) dopo la somministrazione della dose iniziale. I soggetti ritorneranno ancora una volta in giornata 5, 6 o 7 (in base alle preferenze di programmazione) per un prelievo di HCV RNA plasmatico e di un campione per la conservazione. Oltre alle visite ambulatoriali programmate in settimana 1 (giornata 8), 2 e 4, i soggetti arruolati in questo sottostudio ritorneranno in giornata 10 per la valutazione dell’HCV RNA e per il prelievo di un campione di plasma da conservare. Sara` effettuata una raccolta seriale PK in settimana 1 (qualunque momento dalla giornata 8 alla giornata 11, a seconda del basale) e in settimana 4 (giornata 29 � 3 giorni, in relazione al basale). Dopo un digiuno di 8 ore, i soggetti verranno trattenuti per circa 8 ore onde consentire la raccolta di un profilo farmacocinetico seriale, con il campionamento pre-dose (≤ 5 minuti) e a 0,5, 1, 2, 3, 4, 6 e 8 ore dopo il dosaggio del mattino di GS-9190 in cieco, piu` GS-9256 e RBV ai pasti.
ALTRI SOTTOSTUDI: Sottostudio sul registro della resistenza; Sottostudio sul registro SVR a lungo termine.
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| E.3 | Principal inclusion criteria |
| Adults, aged at least 18 with Chronic HCV infection for at least 6 months prior to Baseline (Day 1) in subjects currently positive for HCV RNA and anti-HCV antibody documented by: • a positive anti-HCV antibody test, positive HCV RNA assay, or HCV genotype test at least 6 months prior to Baseline (Day 1) or • a liver biopsy performed prior to Baseline (Day 1) with evidence of chronic HCV infection (i.e., there must be some degree of fibrosis, in addition to inflammation, for the biopsy criterion to be accepted as the historic data for chronic infection) 4. Subjects must have liver biopsy results (performed no more than 2 years prior to screening) indicating the absence of cirrhosis. Alternatively, in countries where the Competent Authority recommends use of a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging), a test result indicating the absence of cirrhosis is allowed, if the test was performed no more than 6 months prior to screening. 5. HCV infection limited to genotype 1a or 1b. 6. Detectable plasma HCV RNA at Screening. 7. BMI between 18 and 36 kg/m2 8. Eligible subjects must also be HCV treatment-na�ve, defined as no prior exposure to IFN-α, RBV, or other approved or experimental HCV therapy, and must be eligible to start standard of care therapy with PEG/RBV. 9. QTcF interval (QT corrected using Fridericia’s formula) must be less than or equal to 450 msec as determined from screening ECG. |
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| E.4 | Principal exclusion criteria |
| Pregnant women or women who may wish to become pregnant. Male with a female partner who is pregnant or is planning to become pregnant within 7 months of anticipated last dose of RBV. Evidence of infection or co-infection with a non-genotype 1 HCV strain. Poorly controlled diabetes mellitus . History of hemoglobinopathy, known retinal disease, sarcoidosis, invasive malignancy within 5 years. Psychiatric illnesses. Co-infection with HBV or HIV. Chronic use of systemic immunosuppressive agents. Presence of autoimmune disorders. Severe chronic obstructive pulmonary disease. History of significant cardiac disease or a family history of Long QT Syndrome. Known cirrhosis. Chronic liver disease of a non-HCV etiology. History of solid organ transplantation. Suspicion of hepatocellular carcinoma. et al. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is SVR (HCV RNA undetectable 24 weeks after cessation of therapy). |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 76 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Ultima visita dell`ultimo soggetto inserito nel sottostudio sul registro SVR a lungo termine |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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