E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus Infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 objectives of this study are:
• To determine the efficacy of treatment with SOF + RBV as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR12)
• To evaluate the safety and tolerability of SOF + RBV as assessed by review of the accumulated safety data, including HIV-RNA and CD4 T-cell percent |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are as follows:
• To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
• To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation
• To evaluate the emergence of viral resistance to SOF during treatment and after treatment discontinuation |
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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 |
Pharmacogenomic Substudy
The objective of this substudy is to identify or validate genetic markers that may predict the natural history of disease, response to therapy and/or the tolerability of medical therapies through genetic discovery research, in subjects who provide their separate and specific consent and provided this substudy is approved locally. |
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E.3 | Principal inclusion criteria |
1. Willing and able to provide written informed consent
2. Male or female, age ≥ 18 years with chronic HCV and HIV-1 infection
3. HCV RNA > 1 x 104 IU/mL at Screening
4. Infection with HCV genotype 1, 2, 3, or 4 as determined at Screening
5. HIV-1 infection confirmed with positive ELISA and Western blot at Screening (if necessary)
6. The subject’s medical records must be sufficient to be categorized on IFN eligibility or prior treatment with PEG/RBV into one of the following categories as defined in Section 6.4.2:
a) Treatment Naïve - IFN-eligible (genotypes 1, 2, 3 and 4)
b) Treatment Naïve - IFN-ineligible (genotypes 1, 2, 3 and 4)
c) Treatment Experienced - IFN Intolerant (genotypes 2 and 3)
d) Treatment Experienced - Non-Response (genotypes 2 and 3)
e) Treatment Experienced - Relapse/Breakthrough (genotypes 2and 3)
7. Confirmation of chronic HCV infection
8. Ability to determine the presence/absence of cirrhosis |
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E.4 | Principal exclusion criteria |
1. Non-genotype 1/2/3/4 or mixed genotype at Screening
2. Genotype 1 or 4 with prior treatment for HCV
3. Poor control with ARV regimen requiring a possible dose modification of therapy within 4 weeks of SOF dosing
4. Prior exposure to a direct-acting antiviral targeting the HCV NS5B polymerase.
5. Pregnant or nursing female or male with pregnant female partner
6. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, α1 antitrypsin deficiency, cholangitis)
7. A new AIDS-defining condition diagnosed within 30 days prior to screening
8. Active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to Baseline
9. Infection with hepatitis B virus (HBV)
10. Contraindication to RBV therapy
11. History of malignancy diagnosed or treated within 5 years |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after cessation of therapy). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 Weeks post last dose of study drug. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include the proportion of subjects with: HCV RNA < LLOQ at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24); HCV RNA < LLOQ on-treatment virologic failure, and change in HCV RNA from baseline through Week 8. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 and 24 Weeks post last dose of study drug. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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 |
Australia |
France |
Germany |
Italy |
Portugal |
Spain |
United Kingdom |
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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
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LVLS, 24 weeks after cessation of therapy |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |