E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Genotype 1 or Genotype 4 Hepatitis C Virus Infection |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Virus Infection |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070218 |
E.1.2 | Term | Hepatitis C virus test positive |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019751 |
E.1.2 | Term | Hepatitis C virus |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 as follows: • To determine the antiviral efficacy of LDV/SOF FDC Tablet as measured by the proportion of subjects who attain SVR at 12 weeks after discontinuation of therapy (SVR12) • To evaluate the safety and tolerability of LDV/SOF FDC as assessed by review of the accumulated safety data |
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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 weeks after discontinuation of study treatment (SVR4) • To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation • To evaluate the emergence of HCV viral resistance to SOF and LDV during treatment and after treatment discontinuation • To evaluate the change in HIV RNA from Day 1 to end of treatment • To assess, among subjects receiving ART for HIV-1, the proportion of subjects that maintain HIV-1 RNA <50 copies/mL while on HCV treatment and at Post-Treatment Week 4 • To assess the change from Day 1 in CD4 T-cell count at the end of treatment and at Post-Treatment Week 4 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. 1) Willing and able to provide written informed consent 2) Male or female, age >/=18 years 3) Body mass index (BMI) >/=18 kg/m2 4) HCV genotype 1 or 4 at Screening as determined by the Central Laboratory. Any non definitive genotype results will exclude the subject from study participation 5) Documented acute hepatitis C infection with detectable HCV-RNA (PCR-assay) with an estimated duration less than 24 weeks as defined in the protocol 6) Confirmed HIV-1 infection and are either: - Receiving an HIV ARV regimen as described in 5.6 with HIV RNA <200 copies/mL or - Not receiving ART with no immediate plans to start ART during the 6 week study duration 7) CD4 T cell count >200/µl at screening in patients under receiving ART, CD4 T cell count >500/µl at screening in patients without ART 8) Females of childbearing potential (as defined in Appendix 4) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to enrollment 9) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 4
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 1) Current or prior history of specific illness/ disorders detailed in the protocol 2) Active HBV infection with positive HBsAg. Subjects not receiving tenofovir-containing ART must also have positive HBV DNA to be excluded. 3) Prior exposure to any IFN, RBV, or other approved or experimental HCV-specific direct acting antiviral agent within the previous 6 months 4) Pregnant or nursing female 5) Chronic liver disease of a non HCV etiology (e.g., hemochromatosis, Wilson’s disease, alfa 1 antitrypsin deficiency, cholangitis) 6) In the opinion of the Investigator, active clinically-relevant alcohol or drug abuse that would present difficulties with protocol compliance 7) Use of any prohibited concomitant medications as described in Section 7.5 or 7.6 8) Drugs disallowed per respective Summary of Product Characteristics depending on subject’s ARV medication 9) ECG with clinically significant abnormalities 10) Serious abnormality on screening blood tests 11) Pregnant or nursing female or male with pregnant female partner 12) Known hypersensitivity to one of the trial drugs or its excipients 13) Any other reason why, in the opinion of the investigator, the patient should not be enrolled in the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is sustained virological response (SVR12), defined as HCV RNA <LLoQ at 12 weeks after completion of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks post last treatment dose |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include the following: • The proportion of subjects with: HCV RNA < LLOQ at 4 weeks after discontinuation of study treatment (SVR4) • The proportion of subjects with HCV RNA < LLOQ on treatment • HCV RNA change from Baseline/Day 1The proportion of subjects with virologic failure |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoints will be assessed on treatment or 4 weeks following discontinuation of treatment |
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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 | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |