E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent Chronic HCV Post Liver Transplant |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C in patients who have received a liver transplant |
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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 |
To determine the antiviral efficacy of combination therapy with GS-7977 + ribavirin for 24 weeks in subjects with recurrent HCV post liver transplant as measured by sustained virologic response 12 weeks after discontinuation of therapy (SVR12 defined as HCV RNA < lower limit of quantitation [LLoQ] 12 weeks after last dose of study drug). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of this regimen in this patient population
• To determine the proportion of subjects who attain sustained virologic response at 4, 24 and 48 weeks after discontinuation of therapy (SVR4, SVR24 and SVR48)
• To evaluate the emergence of viral resistance to GS-7977 during and after treatment discontinuation.
• To evaluate the kinetics of circulating HCV RNA during and after treatment |
|
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 |
Pharmacogenomics substudy
To identify or validate genetic 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, in subjects who provide a separate and specific consent |
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E.3 | Principal inclusion criteria |
1. Willing and able to provide written informed consent
2. Males or females, age ≥ 18 years old
3. Subjects with evidence of chronic HCV (all genotypes) documented pretransplantation
4. HCV RNA ≥ 10000 IU/mL at screening
5. Absence of organ rejection as documented by post transplant liver biopsy taken no more than 12 months prior to Baseline/Day 1 visit
6. Primary or secondary (retransplant), liver alone or liver and kidney transplant recipient from deceased or living donor (regardless of the HCV status of the liver donor)
7. Liver transplant ≥ 6 months and ≤ 150 months prior to screening
8. Naïve to all nucleotides/nucleoside treatments for chronic HCV infection
9. A body mass index (BMI) of ≥18 kg/m2 |
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E.4 | Principal exclusion criteria |
1. Multi-organ transplant that includes heart or lung recipient
2. Subjects with de novo or recurrent Hepatocellular Carcinoma (HCC) post transplant based on center specific screening protocol
3. Current use of corticosteroids at any dose ≥ 5mg of prednisone/day (or equivalent dose of corticosteroid)
4. Child-Pugh-Turcotte Score CPT > 7 at screening
5. MELD score > 17 at screening
6. Recipient of ABO incompatible organ
7. Histological evidence of unresolved rejection
8. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) at screening
9. Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis
10. Serum creatinine >2.5x upper limit of normal or stage 4 chronic kidney disease (CrCl <30ml/min)
18. Treatment with IFN, RBV, telaprevir or boceprevir or any other approved or experimental medication with known anti-HCV activity within 3 months prior to Baseline/Day 1 visit
19. Screening ECG with clinically significant abnormalities
20. Participation in a clinical study with an investigational drug, or biologic within 3 months prior to first dose administration at the Baseline/Day 1 Visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is SVR12 (HCV RNA < lower limit of quantitation [LLoQ] 12 weeks after last dose of study drug) for subjects in the Full Analysis Set. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after last dose of study drug |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include the proportion of subjects who attain sustained virologic response at 4, 24 and 48 weeks after discontinuation of therapy (SVR4, SVR24 and SVR48); proportion of subjects who have HCV RNA < LLoQ by visit while on treatment; absolute and change from baseline in HCV RNA through Week 8; and virologic failure. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4, 24 and 48 weeks after 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) | 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.8.3 |
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 | 3 |
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 |
New Zealand |
United States |
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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
|
LVLS (48 weeks after last dose of study drug) |
|
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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |