| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008912 |
| E.1.2 | Term | Chronic hepatitis C |
|
| 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 objective of the trial is to assess the activity of telaprevir on HCV genotype 4 replication by evaluating early viral kinetic parameters, when administered during 2 weeks, alone or in combination with Peg-IFN alfa2a and RBV. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- to evaluate the single-dose and steady-state pharmacokinetics of telaprevir and VRT-127394, and the pharmacokinetic-pharmacodynamic relationship of telaprevir in subjects chronically infected with HCV genotype 4;
- to evaluate the pharmacokinetics of Peg-IFN alfa2a and RBV alone and in combination with telaprevir;
- to assess and characterize phenotype and genotype resistant variants potentially arising after 2 weeks of telaprevir treatment (with or without Peg-IFN alfa2a and RBV), during the 48-week standard treatment phase, and during the 24-week follow-up phase, in subjects chronically infected with HCV genotype 4;
- to evaluate the safety and tolerability of a 2-week treatment with telaprevir with or without PegIFN alfa2a and RBV in subjects chronically infected with HCV genotype 4.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and female subjects, 18 to 65 years of age, inclusive.
2. Subjects with chronic genotype 4 hepatitis C infection.
Chronic disease status must be confirmed by a diagnosis of hepatitis C > 6 months before the screening period.
3. Plasma HCV RNA level of > 10000 IU/mL at screening.
4. Subject has never received treatment for HCV (including investigational products).
5. Screening laboratory values of the following variables must meet the acceptable values defined below:
Laboratory variable Acceptable values
Absolute neutrophil count >= 1500/mm3
Platelet count >= 100000/mm3
Hemoglobin Within normal range
All other hematology and biochemistry results must show no clinically significant abnormalities, in the opinion of the investigator.
6. Subjects judged to be in good health (besides HCV infection), in the opinion of the investigator, on the basis of medical history and physical examination (including vital signs and screening ECG), with any chronic medical conditions under stable medical control.
7. If heterosexually active, female subjects of childbearing potential must agree to the use of two effective methods of contraception from screening until 4 months after last dose of RBV, as outlined in Section 5.2.4.
If heterosexually active, non-vasectomized male subjects who have a female partner of childbearing potential must agree to the use of the two effective methods of contraception from screening until 7 months after last dose of RBV, as outlined in Section 5.2.4.
Note: Oral contraceptives may not be reliable when taking telaprevir. Therefore, in order to be eligible for this trial, female subjects must use 2 barrier methods during telaprevir/placebo treatment and the subsequent month. Barrier contraceptives include the following methods: male condom, diaphragm with spermicidal gel, cervical cap, or female condom (note that the female condom should not be used simultaneously with a latex male condom because the friction between the condoms may cause the condoms to break). As of one month after completion of telaprevir/placebo treatment until 24 weeks after the last dose of RBV, oral contraceptives can be used as one of the 2 required efficient methods of birth control.
Note: The use of birth control methods does not apply if the male sexual partner has undergone a vasectomy or if the female sexual partner has had a bilateral oophorectomy, or a total hysterectomy, or if she is post-menopausal for at least 2 years.
8. Subject is willing to refrain from the concomitant use of any medications or substances noted in Section 5.3.11.
9. Subject has signed the ICF voluntarily before the first trial-related activity.
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|
| E.4 | Principal exclusion criteria |
1. Subject has a concomitant medical condition that in the opinion of the investigator could influence the results of the trial or that could represent an additional risk for the administration of the study medication to the subject.
2. Subject has medical contraindications to the administration of an IFN (Peg-IFN alfa2a in particular) or RBV treatment, including but not limited to the following:
- abnormal thyroid stimulating hormone (TSH) levels or poorly controlled thyroid function;
- evidence of clinically significant cardiac dysfunction;
- history of psychiatric disorders determined by the investigator to contraindicate the use of IFN-based therapy;
- Evidence of autoimmune disease;
- History of hemoglobinopathies.
3. Subject has a history or evidence of cirrhosis, end-stage or decompensated liver disease, or hepatocellular carcinoma as shown by screening laboratory results of any of the following:
- international normalized ratio (INR) ³ 1.7;
- serum albumin < 3.5 g/dL;
- serum total bilirubin > 1.8 times the upper limit of laboratory normal range (ULN), unless isolated and for subjects with Gilbert’s Syndrome;
- history of ascitis, hepatic encephalopathy, or bleeding esophageal varices;
- alfa fetoprotein (AFP) > 50 ng/mL, unless absence of a mass can be documented on an ultrasound or Magnetic Resonance Imaging (MRI) within the screening period.
4. Subject has history or suspicion of alcohol, barbiturate, or amphetamine recreational or narcotic drug use, which in the investigator’s opinion would compromise the subject’s safety and/or compliance with study procedures.
5. Subject has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection.
6. Women who are pregnant, planning to become pregnant, or breastfeeding, and partners of women who are pregnant or breastfeeding.
7. Subject has hypersensitivity to tartrazine.
8. Subject participated in any clinical trial for an investigational drug within 90 days before drug administration or participated in more than 2 drug studies in the last 12 months (exclusive of the current trial).
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Plasma Hepatitis C Virus RNA level |
|
| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| 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 | No |
| 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 | Information not present in EudraCT |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 3 |
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