| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C Virus |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic Hepatitis C Virus |
|
| 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 | 16.0 |
| 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 |
To evaluate the antiviral efficacy of a quadruple drug regimen (VX-222,
telaprevir, Peg-IFN and RBV) in subjects with genotype 1 CHC with
compensated cirrhosis, who are treatment naive or were nonresponders
(partial or null) or relapsers to previous Peg-IFN/RBV therapy. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of the quadruple regimen in
subjects with compensated cirrhosis
To assess the efficacy of quadruple regimen across interleukin-28B (IL-
28B) genotypes
To characterize HCV variants in subjects on the quadruple regimen who
have treatment failure
To characterize the pharmacokinetics (PK) of VX-222 and telaprevir in
the quadruple regimen in subjects with compensated cirrhosis |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
must be between the ages of 18 and 70 years
- Subjects must have genotype 1 CHC and laboratory evidence of HCV
infection for at least 6 months before the Screening Visit
- Subjects must have documentation of compensated cirrhosis
- Subjects must fit one of the following categories:
• Treatment-naïve: never received treatment for hepatitis C
• Prior null responder: had <2-log10 decrease from baseline in HCV RNA
concentration at the Week 12 assessment after prior Peg-IFN/RBV
treatment of at least 12 weeks.
• Prior partial responder: had a ≥2-log10 decrease in HCV RNA
concentration at the Week 12 assessment after prior Peg-IFN/RBV
treatment of at least 12 weeks but never had undetectable HCV RNA
levels while on treatment.
• Prior relapser: had undetectable HCV RNA at EOT after prior Peg-
IFN/RBV treatment of at least 12 weeks but detectable HCV RNA after
the end of prior treatment.
For null and partial responders, the Week 12 assessment of HCV RNA
response used should be from a sample collected between no earlier
than Week 11 and no later than Week 16. If more than one assessment
from this time period is available, the assessment closest to Week 12
should be used.
The following information related to the virologic response to the last
course of Peg IFN/RBV therapy, if applicable, must be available in the
medical records of the subject:
• HCV RNA results before the start of treatment and at Week 12
assessment after start of treatment or documentation of the total
treatment duration and log fold-change in HCV RNA.
• Last dose of prior therapy must be at least 12 weeks before first dose
of study drug given under this protocol.
- Subject s must have plasma HCV RNA of ≥4.0 log10 IU/mL (10000
IU/mL).
|
|
| E.4 | Principal exclusion criteria |
- Any previous treatment with an investigational drug or drug regimen
for the treatment of hepatitis C, or previous treatment with an approved
protease inhibitor
-History of any illness that, in the opinion of the investigator or general
practitioner might confound the results of the study or pose an
additional risk to the subject
- Any contraindication to Peg-IFN or RBV therapy, or history of severe
AEs while on Peg-IFN or RBV
- Child-Pugh Score ≥7, or other clinical evidence of hepatic
decompensation
- Any other cause of significant liver disease in addition to hepatitis C
- Diagnosed or suspected hepatocellular carcinoma
- History of organ transplant, with the exception of corneal transplants
and skin grafts
- A medical condition that requires frequent or prolonged use of systemic
corticosteroids or immunosuppressive drugs
- History of acute pancreatitis
- History or other clinical evidence of chronic pulmonary disease
associated with functional impairment
- History of other evidence of sever retinopathy or clinically significant
ophthalmological disorder
- History of illicit substance or alcohol abuse within 1 year before the
Screening Visit
- Blood donation of approximately 1 pint (500 mL) within 56 days before
dosing
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of subjects who have an SVR (i.e., sustain an HCV RNA concentration below the lower limit of quantitation at 12 weeks after last planned dose of treatment (SVR12) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
-The safety and tolerability as assessed by AEs, vital signs, 12-lead
electrocardiograms (ECG), and laboratory assessments (serum
chemistry, hematology, and urinalysis)
- Proportion of subjects who have an SVR24 weeks after the last planned
dose of the study drug (SVR24)
- Proportion of subjects who achieve undetectable HCV RNA at Weeks
2,4,8, and 12 and <LLOQ at the end of treatment
-Proportion of subjects who have on-treatment virologic failure, defined
as subjects who either meet a futility rule or complete assigned
treatment duration and have detectable HCV RNA at the end of study
drug treatment
- Proportion of subjects who relapse at end of treatment
- The association of IL-28B genotype with SVR12
- The amino acid sequence of the NS3 and NS5B proteins in subjects who
have treatment failure
- VX-222, telaprevir, RBV plasma concentrations; and Peg-IFN serum
concentrations |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | 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
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 |
| Belgium |
| Canada |
| Germany |
| Poland |
| United Kingdom |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 5 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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