E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic hepatitis C infection |
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E.1.1.1 | Medical condition in easily understood language |
Chronic hepatitis C 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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019752 |
E.1.2 | Term | Hepatitis C virus (HCV) |
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 |
to determine the efficacy of telaprevir administered as 750 mg every 8 hours (q8h) in combination with pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) in genotype 1 chronic HCV infected liver transplant patients as measured by sustained virologic response (SVR12planned). SVR12planned is defined as
having HCV ribonucleic <25 IU/mL acid (RNA) level 12 weeks after the last planned dose of study medication. |
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E.2.2 | Secondary objectives of the trial |
- to compare the SVR rate from this study to a historical control SVR rate derived from the literature in subjects treated with Peg-IFN and RBV;
- to evaluate HCV RNA levels and responses over time, on treatment and during follow-up;
- to evaluate changes in liver graft biopsy histology comparing the last pre-treatment biopsy to the 24-week post-treatment biopsy;
- to evaluate safety and tolerability of telaprevir in combination with Peg-IFN-alfa-2a, RBV, and tacrolimus (TAC) or cyclosporin A (CsA);
- to evaluate the pharmacokinetics (PK) of telaprevir and concentrations of TAC or CsA;
- to evaluate dose titration requirements for TAC and CsA;
- to evaluate the incidence of liver graft rejection;
- to evaluate relapse rates and virologic failure rates;
- to evaluate changes from baseline in the amino acid sequence of HCV NS3-4A protease. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- First time liver transplant recipient whose primary pre-transplant diagnosis was chronic hepatitis C genotype 1
- More than 6 months to 10 years post-liver transplant - Patient did or did not receive treatment for HCV prior to liver transplantation
- Patient must agree to have a liver graft biopsy within the screening period with exception made if recent serial biopsy with stable stage of hepatic fibrosis
- A female patient of childbearing potential and a nonvasectomized male patient who has a female partner of childbearing potential must agree to the use of 2 effective methods of birth control from screening until 6 months (female patient) or 7 months (male patient) after the last dose of ribavirin |
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E.4 | Principal exclusion criteria |
- Patient is currently infected or co-infected with HCV of another genotype than genotype 1
- Patient received treatment for hepatitis C following liver transplantation
- Patient has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C
- Patient has human immunodeficiency virus or hepatitis B virus coinfection
- Patient has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients achieving sustained virologic response (SVR) 12planned (SVR12planned is defined as having plasma HCV (hepatitis C virus) RNA (ribonucleic acid) level <25 IU/mL 12 weeks after the last planned dose of study medication.) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Number of patients achieving SVR12planned(c) (SVR12planned(c) is defined as having undetectable plasma HCV RNA levels 12 weeks after the last planned dose of study drugs.)
- Number of patients achieving SVR24planned (SVR24planned is defined as having plasma HCV RNA levels <25 IU/mL 24 weeks after the last planned dose of study medication.)
- Number of patients achieving SVR24planned(c) (SVR24planned(c) is defined as having an undetectable plasma HCV RNA level 24 weeks after the last planned dose of study medication.)
- Number of patients having an undetectable HCV RNA level at Week 4 of treatment
- Number of patients having an undetectable HCV RNA level at Week 12 of treatment
- Number of patients having undetectable HCV RNA levels at Week 4 and Week 12 of treatment
- Number of patients having an undetectable HCV RNA level at the actual end of treatment
- Number of patients having an undetectable HCV RNA level at the planned end of treatment
- Number of patients having < 25 IU/mL at the planned end of treatment
- Number of patients with ontreatment virologic failure
- Number of patients with relapse at actual end of treatment
- Number of patients with relapse at planned end of treatment
- Number of patients with viral breakthrough
- Change from baseline in log HCV RNA values
- Number of patients who have changes in liver graft biopsy histology
- Number of patients with adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Week 60
- Week 72
- Week 72
- Week 4
- Week 12
- Week 4 and Week 12
- Up to week 48
- Week 48
- Week 48
- Up to week 48
- Up to week 48
- Up to week 48
- Up to week 48
- Up to week 48
- Up to week 72
- Up to week 72 |
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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) | 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 | No |
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 | 23 |
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 | 1 |
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 | 1 |
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 |