E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Genotype 1 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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019751 |
E.1.2 | Term | Hepatitis C virus |
E.1.2 | System Organ Class | 100000004848 |
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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 antiviral efficacy of combination treatment with sofosbuvir/GS-5885 fixed-dose combination ± RBV as measured by the proportion of subjects with SVR
12 weeks after discontinuation of therapy (SVR12).
• To evaluate the safety and tolerability of each treatment regimen 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:
• 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 sofosbuvir and GS-5885 during treatment and after treatment discontinuation
• To characterize the steady state pharmacokinetics of study drugs
• To assess the effect of treatment on health related quality of life |
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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 |
Pharmacokinetic Substudy:
An intensive serial PK sample collection will be performed at the Week 2 or Week 4 on-treatment
visit to determine the steady-state pharmacokinetics of sofosbuvir (and its metabolites GS-566500 and GS-331007), GS-5885, and RBV (if appropriate).
Pharmacogenomics Substudy:
The objective of this substudy is to identify or validate host markers that may be predictive of the natural history of disease, virologic response to therapy and/or the tolerability of medical therapies through genetic discovery research (e.g., pharmacogenomics), in subjects who provide their separate and specific consent. |
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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
3) Body mass index (BMI) ≥ 18
4) HCV RNA ≥ 104 IU/mL at Screening
5) HCV treatment-naïve
6) HCV genotype 1a, 1b, or mixed 1a/1b at Screening.
7) Confirmation of chronic HCV infection
8) Cirrhosis determination [up to 20% of study subjects may have cirrhosis]
9) Liver imaging within 6 months of Baseline/Day 1 to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis
10) Screening ECG without clinically significant abnormalities
12) Subject has not been treated with any investigational drug or device within 30 days of the Screening visit.
14) All male study participants must agree to consistently and correctly use a condom while their female partner agrees to use 1 highly effective method of birth control from the date of screening until 7 months after their last dose of RBV or 90 days after their last dose of study drug if not taking RBV.
15) Male subjects must agree to refrain from sperm donation from the date of screening until at least 7 months after the last dose of RBV or 90 days after their last dose of study drug if not taking RBV.
16) Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator.
17) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments. |
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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;
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) Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage);
e) Solid organ transplantation;
f) Significant pulmonary disease, significant cardiac disease or porphyria;
g) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years;
h) Malignancy diagnosed or treated within 5 years;
i) Significant drug allergy (such as anaphylaxis or hepatotoxicity).
2) Pregnant or nursing female or male with pregnant female partner.
3) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis).
4) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
5) Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1
6) Clinically-relevant drug abuse within 12 months of screening.
7) Alcohol misuse as defined by a Alcohol Use Disorders Identification Test (AUDIT) score ≥ 8
8) Contraindications to RBV therapy, including significant history of clinically significant hemoglobinopathy (e.g., sickle cell disease, thalassemia).
9) Use of any prohibited concomitant medications within 21 days of the Baseline/Day 1 visit.
10) Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day).
11) Known hypersensitivity to RBV, GS-5885, sofosbuvir, or formulation recipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is sustained viral response 12 weeks post last dose of any treatment (HCV RNA <LOQ 12 weeks after cessation of therapy) in the ITT population (SVR12). |
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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) |
1) Safety: Adverse events (AE), safety labs, electrocardiograms (ECGs) and vital signs
2) Sustained viral response 24 weeks post last dose of any treatment (HCV RNA <LOQ 24weeks after cessation of therapy) in the ITT population (SVR24). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety and tolerability will be assessed throughout the study
SVR24 will be assessed 24 weeks post the last treatment dose |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Verträglichkeit |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Comparative treatment regimens and durations |
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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
| 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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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, defined as last vist 24 weeks after discontinuation 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 | 1 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |