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 | 19.1 |
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 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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 |
|
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 |
To determine the efficacy of treatment with SOF/VEL/VOX FDC for 12 weeks as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR12)
To evaluate the safety and tolerability of treatment with SOF/VEL/VOX FDC |
|
E.2.2 | Secondary objectives of the trial |
To determine the proportion of subjects who attain SVR at 4 weeks after cessation of treatment (SVR4) To evaluate the proportion of subjects with virologic failure To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment To evaluate the emergence of viral resistance to SOF, VEL, and VOX during treatment and after cessation of treatment |
|
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 ≥18 years 3) HCV RNA ≥ LLOQ at Screening 4) Received SOF/VEL/VOX for 8 weeks or SOF/VEL for 12 weeks in GS-US-367-1172 (POLARIS-2), GS-US-367-1173 (POLARIS-3), or GS-US-367-1170 (POLARIS-4), or received HCV treatment with a DAA-based regimen in another Gilead-sponsored study, with approval from Gilead Sciences prior to Screening 5) Cirrhosis Determination 6) Liver imaging within 6 months prior to Day 1 is required in cirrhotic subjects to exclude hepatocellular carcinoma (HCC) 7) Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to enrollment 8) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception 9) Lactating females must agree to discontinue nursing before starting study drug 10) Subject must be of generally good health, with the exception of chronic HCV infection, 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) Current or prior history of any of the following: a. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded b. Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug c. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy d. Hepatic decompensation (e.g., clinical ascites, encephalopathy, and/or variceal hemorrhage) e. Solid organ transplantation f. Significant cardiac disease g. Unstable psychiatric condition including hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within 2 years prior to Screening h. Malignancy within the 5 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection. Subjects under evaluation for possible malignancy are not eligible. i. Significant drug allergy (e.g., hepatotoxicity) 2) Screening ECG with clinically significant abnormalities 3) Subjects with laboratory parameters at screening as defined in the protocol 4) Prior treatment with SOF/VEL/VOX±RBV for ≥12 weeks 5) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alfa-1 antitrypsin deficiency, cholangitis) 6) Infection with human immunodeficiency virus (HIV) 7) Hepatitis B surface antigen positive (HBsAg+) at Screening 8) Clinically-relevant alcohol or drug abuse within 12 months of Screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator 9) Use of any prohibited concomitant medications 10) Known hypersensitivity to the study drug, the metabolites, or formulation excipient. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is SVR12 in the Full Analysis Set (FAS) population.
The primary safety endpoint is any AE leading to permanent discontinuation of study drug. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks post last treatment dose |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints include the following: - SVR4 - The proportion of subjects with HCV RNA < LLOQ on treatment - The proportion of subjects with virologic failure - HCV RNA change from Baseline/Day 1 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy endpoints will be assessed on treatment and 4 and 12 weeks following discontinuation of treatment |
|
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 | 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) | 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 | 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
| 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 | 4 |
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 |
Canada |
France |
Germany |
New Zealand |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
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 | 0 |
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 |