| 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 | 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 | 10022891 - Investigations |
|
| 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 is to demonstrate the non-inferiority in sustained viral response (SVR24planned) of telaprevir administered as 1125 mg twice daily (b.i.d.) versus 750 mg every 8 hours (q8h) in combination with pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) in treatment-naïve subjects with chronic HCV genotype 1 infection. SVR24planned is defined as having undetectable plasma HCV ribonucleic acid (RNA) levels 24 weeks after the last planned dose of study drugs. |
|
| E.2.2 | Secondary objectives of the trial |
- to evaluate tolerability and safety of telaprevir when administered as 750 mg q8h or 1125 mg b.i.d. in combination with Peg-IFN-alfa-2a and RBV;
- to investigate the effect of IL28B genotype on viral response;
- to evaluate pharmacokinetics of telaprevir, Peg-IFN-alfa-2a, and RBV and pharmacokinetic-pharmacodynamic relationships for safety and efficacy;
- to evaluate changes from baseline in the amino acid sequence of the HCV NS3-4A region. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is a man or a woman between 18 and 70 years of age, inclusive.
2. Subject has chronic HCV infection genotype 1 with HCV RNA level > 1,000 IU/mL. Genotype must be confirmed during screening. Chronic infection status must be confirmed by detectable HCV RNA more than 6 months before the screening visit or by histological diagnosis of chronic hepatitis based on the liver biopsy.
3. Subjects should not have had any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C.
4. Subject is judged to be medically stable on the basis of physical examination, medical history, vital signs, and 12 lead electrocardiogram (ECG) performed at screening.
5. Subject must have documentation of a liver biopsy within 2 years before the screening visit or the subject must agree to have a biopsy performed within the screening period. If a biopsy more than 2 years prior to screening has already demonstrated histological cirrhosis, the biopsy does not need to be repeated if the biopsy report can be provided.
6. Subjects with cirrhosis should have serum alpha-fetoprotein (AFP) ≤ 50 ng/mL and normal abdominal ultrasound. If AFP > 50 ng/mL or ultrasound abnormal, absence of a mass must be demonstrated by a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan. If a subject was screened for hepatocellular carcinoma within 5 months of the screening visit, this screening (ultrasound, CT, MRI) can be used to fulfill the inclusion criterion.
7. If heterosexually active, a female subject of childbearing potential and a nonvasectomized male subject who has a female partner of childbearing potential must agree to the use of 2 effective methods of contraception from screening onwards until 6 months (female subject) or 7 months (male subject) after the last dose of RBV.
Note: Hormonal contraceptives may not be reliable when taking telaprevir. Therefore, to be eligible for this study, subjects should use 2 other effective birth control methods during telaprevir treatment and for 2 months after the last intake of telaprevir.
8. Subject or female partner is not pregnant, planning to become pregnant, or breastfeeding.
All female subjects must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
9. Subject is willing/able to adhere to the prohibitions and restrictions specified in this protocol.
10. Subject must have signed an Informed Consent Form (ICF) including consent to IL28B testing, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
11. Subjects should agree not to participate in other clinical studies for the duration of their participation in this study, except for noninterventional or observational studies and only after prior approval of the sponsor. |
|
| E.4 | Principal exclusion criteria |
1. Subject is infected or co-infected with HCV of another genotype than genotype 1.
2. Subject is infected with HCV genotype 1 exhibiting more than one subtype.
Note: exclusion criterion 2 is deleted from the protocol as per general protocol amendment III dated 10 Feb 2011.
3. Subject presents a contraindication to the administration of Peg-IFN-alfa-2a or RBV
4. Subject has known allergies, hypersensitivity, or intolerance to telaprevir or its excipients
5. Subject uses disallowed therapies
6. Subject has a pre-existing psychiatric condition
7. Subject has history of decompensated liver disease: history of ascites, hepatic encephalopathy, or bleeding esophageal varices
8. Subject shows evidence of significant liver disease in addition to hepatitis C, which may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, Nonalcoholic Steatohepatitis (NASH), or primary biliary cirrhosis.
9. Subject has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma).
10. Subject has history of seizure disorders (except for childhood seizures that have not persisted).
11. Subject has congenital or acquired prolonged QT interval, a history of nonsustained or sustained ventricular tachycardia, or a history of drug-induced QT prolongation and/or Torsade de Pointes.
12. Subject has history of organ transplant that requires chronic immunosuppression. Note: corneal, skin, and hair grafts are allowed.
13. Subject has a medical condition that requires chronic or intermittent use of systemic corticosteroids (e.g., severe asthma, severe arthritis, or autoimmune conditions, organ transplantation, adrenal insufficiency, etc.).
14. Subject has history or other evidence of clinically significant retinopathy or ophthalmological disorder
15. Subject has clinical evidence of chronic pulmonary disease associated with functional impairment.
16. Subject has evidence of hemophilia or other bleeding disorder.
17. Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis.
18. Subject has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co infection.
19. Subject has a history of acute or chronic pancreatitis.
20. Knowledge or suspicion exists of alcohol, barbiturate, or amphetamine recreational or narcotic drug use (current or within 2 years prior to the screening visit) that in the investigator’s opinion would compromise the subject’s safety and/or compliance with study procedures.
21. Subject has a condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting or performing study requirements.
22. Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
23. Subject received an investigational drug or used an investigational medical device within 90 days before the planned start of treatment.
24. Subject has a grade 4 laboratory abnormality |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective is to demonstrate the non-inferiority in sustained viral response (SVR24planned) of telaprevir administered as 1125 mg twice daily (b.i.d.) versus 750 mg every 8 hours (q8h) in combination with pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) in treatment-naïve subjects with chronic HCV genotype 1 infection. SVR24planned is defined as having undetectable plasma HCV ribonucleic acid (RNA) levels 24 weeks after the last planned dose of study drugs |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Yes |
| 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 | 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 | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 150 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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