E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C virus infection |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 17.0 |
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 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
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 |
|
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 evaluate the safety of sofosbuvir (SOF) 200mg or 400mg + ribavirin (RBV) for 24 weeks as assessed by review of the accumulated safety data in each treatment arm
* To evaluate the efficacy of sofosbuvir (SOF) 200mg or 400mg + ribavirin (RBV) for 24 weeks measured by the proportion of subjects with renal insufficiency who have achieved a sustained viral response 12 weeks after treatment discontinuation (SVR12) in each treatment arm
* To evaluate the steady state pharmacokinetics of SOF and its metabolites upon dosing SOF 200mg or 400mg in subjects with renal insufficiency |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
* To evaluate the proportion of subjects with renal insufficiency who attain SVR at 4 and 24 weeks after discontinuation of treatment (SVR4 and SVR24)
* To evaluate the kinetics of plasma HCV RNA during and after treatment discontinuation
* To evaluate the emergence of viral resistance to SOF during and after treatment discontinuation |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Willing and able to provide written informed consent
2) Male or female, age greater or equal to 18 years
3) Chronic HCV infection
4) Infection with HCV GT 1 or 3 as determined at Screening
6) INR less than or equal to 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR.
7) A negative serum pregnancy test for female subjects of childbearing potential
8) Male subjects and female subjects of childbearing potential must agree to use protocol specified method(s) of contraception
9) Lactating females must agree to discontinue nursing before administration of study drug
10) Subject must be of generally good health as determined by the Investigator
11) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments. |
|
E.4 | Principal exclusion criteria |
1) BMI < 18
2) Prior exposure to an direct-acting antiviral targeting the HCV NS5B polymerase
3) Prior null response to PEG+RBV therapy
4) Male with pregnant female partner
5) Chronic liver disease of a non-HCV etiology
6) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
7) Unstable psychiatric condition
8) Significant cardiac disease
9) Clinically significant abnormality on ECG at Screening
10) History of clinically significant hemoglobinopathy
11) History of porphyria
12) Malignancy within the 5 years prior to screening
13) Chronic use of systemically administered immunosuppressive agents
14) Clinically-relevant drug or alcohol abuse within 12 months of Screening.
15) Current or prior history of clinical hepatic decompensation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety endpoints include incidences of AEs, laboratory, 12-lead ECG, and vital sign abnormalities.
The primary PK endpoints are parameters AUCtau, Cmax, and Ctau for analytes SOF, its metabolites and RBV as applicable.
The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after discontinuation of therapy). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The safety and PK endpoints are evaluated during the course of treatment. The efficacy endpoint is evaluated 12 weeks after discontinuation of therapy. |
|
E.5.2 | Secondary end point(s) |
Secondary PK endpoints are parameters AUClast, Clast, Tmax, Tlast, λz, and t1/2 for analytes SOF, its metabolites and RBV as applicable.
Secondary efficacy endpoints include the proportion of subjects with SVR4 and SVR24, the proportion of subjects with virologic failure including viral breakthrough and relapse. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The PK endpoints are evaluated during the course of treatment. The efficacy endpoints are evaluated 4 and 24 weeks after discontinuation of therapy. |
|
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 | No |
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 | 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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
2 doses of SOF - 200mg and 400mg - in 2 pt pops (severe renal insuff. and end-stage renal disease) |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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 |
Argentina |
Austria |
Germany |
Netherlands |
New Zealand |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |