E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CHRONIC GENOTYPE 1 HEPATITIS C |
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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 |
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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 demonstrate the superior efficacy of telaprevir in combination with Peg-IFN alfa-2a and RBV compared to standard treatment in subjects with chronic HCV genotype 1 infection who failed prior treatment with Peg-IFN plus RBV. |
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E.2.2 | Secondary objectives of the trial |
To evaluate: - the effect of delayed start of telaprevir on the efficacy (SVR and secondary parameters) of telaprevir in combination with Peg-IFN alfa-2a and RBV; − the efficacy of 2 telaprevir-based regimens versus standard treatment for the 2 subgroups within the non-responders, namely (1) the null-responders (defined as subjects who had < 2 log drop in HCV RNA at Week 12 of previous therapy) and (2) the partial responders (defined as subjects who had ≥ 2 log drop in HCV RNA at Week 12 of previous therapy, but who never achieved undetectable HCV RNA levels while on treatment); − safety and tolerability of telaprevir in combination with Peg-IFN alfa-2a and RBV; − changes from baseline in the HCV NS3 protease domain; − the pharmacokinetics of telaprevir, telaprevirs R-diastereomer VRT-127394, Peg-IFN alfa-2a, and RBV, and the pharmacokinetic-pharmacodynamic relationship with virologic response, safety and tolerability parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is male or female, 18 to 70 years of age, inclusive. 2. Subject has chronic hepatitis C infection genotype 1 with HCV RNA level ≥ 1000 IU/mL. Genotype must be confirmed during screening. Chronic infection status must be confirmed by diagnosis of HCV > 6 months before the screening period. 3. Subject failed at least 1 prior course of Peg-IFN/RBV therapy, defined as: − Subject had an undetectable HCV RNA level (by branched-chain DNA [bDNA], reverse transcription-polymerase chain reaction [RT-PCR], or transcription mediated amplification [TMA]-based assay) at the end (6 weeks or less after the last dose of medication) of a prior course of at least 42 weeks of Peg-IFN/RBV therapy but did not achieve SVR (viral relapser); or − Subject never had an undetectable HCV RNA level (by bDNA, RT-PCR, or TMA-based assay) during or at the end of a prior course of at least 12 weeks of Peg-IFN/RBV therapy (null-responder and partial responder). Subject must have received 80% or more of the intended dose of Peg-IFN/RBV. The following information related to the virologic response to the last course of Peg-IFN/RBV therapy (that qualifies as an adequate course as defined above) must be available in the medical records of the subject: - start and end date of the previous treatment course; - HCV RNA values at start of treatment (all subjects), at 12 weeks after start of treatment (all subjects), at end of treatment (all subjects), and during follow-up (relapsers); - HCV RNA assay used and limit of detection. 4. Subject must have received the last dose of Peg-IFN or RBV at least 12 weeks before the screening visit. 5. Subject is 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 electrocardiogram [ECG]), with any chronic medical conditions under stable medical control. 6. Subject must have had a liver biopsy within 18 months prior to the screening visit and the biopsy report should be available, or he/she should agree to have a biopsy performed within the screening period. 7. Subjects with cirrhosis should have serum alpha-fetoprotein (AFP) ≤ 50 ng/mL and normal abdominal ultrasound. If AFP > 50 ng/mL or ultrasound abnormal, subjects must have a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan to exclude hepatocellular carcinoma. 8. If heterosexually active, a female subject of childbearing potential and a non-vasectomized 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. |
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E.4 | Principal exclusion criteria |
1. Subject is a previous non-responder that is classified as a viral breakthrough case i.e., subject had an undetectable HCV RNA level (by bDNA, RT-PCR, or TMA-based assay) during prior course of Peg-IFN/RBV therapy but regained detectable HCV RNA before therapy ended. 2. Subject is infected with HCV genotype 1 exhibiting more than one subtype. 3. Subject has HCV genotype 1 and exhibits co-infection with any other genotype. 4. Subject discontinued prior course(s) of Peg-IFN/RBV therapy due to a tolerance issue instead of lack of response. 5. Subject has any contraindication to the administration of Peg-IFN alfa-2a or RBV, including but not limited to any of the following: − hypersensitivity to Peg-IFN alfa-2a, RBV, or any of their components; − hemoglobinopathies (including thalassemia major, sickle-cell disease); − history or clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction, significant arrhythmia) and/or clinically significant ECG abnormalities; − abnormal thyroid function that cannot be controlled effectively by medication; − poorly controlled diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening; − creatinine clearance ≤ 50 mL/min at screening; − antinuclear antibody (ANA) titer ≥ 1:640 at screening, evidence of autoimmune-mediated disease (e.g., Crohns disease, ulcerative colitis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis), and/or evidence of autoimmune hepatitis. 6. Subject has a pre-existing psychiatric condition that could interfere with the subjects participation in and completion of the trial, including but not limited to: − severe depression or hospitalization for depression; − schizophrenia, bipolar illness, severe anxiety, or personality disorder; − a period of disability or impairment due to a psychiatric disease within the past 5 years. 7. Subject has history of decompensated liver disease: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, and/or any of the following screening laboratory results: − International Normalized Ratio (INR) of ≥ 1.5; − Serum albumin < 3.3 g/dL; − Serum total bilirubin > 1.8 times upper limit of laboratory normal range (ULN), unless isolated and for subjects with Gilberts Syndrome. 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, Wilsons 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. 11. Subject has history of organ transplant that requires chronic immunosuppression. 12. Subject has a medical condition that requires use of systemic corticosteroids (e.g. severe asthma, severe arthritis, or autoimmune conditions, organ transplantation, adrenal insufficiency, etc.). 13. Diabetic or hypertensive subject with clinically significant ocular exam findings, e.g., retinopathy, cotton wool spots, and optic nerve disorder. 14. Subject has history or other clinical evidence of chronic pulmonary disease associated with functional impairment. 15. Subject has hemophilia. 16. Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis. 17. Subject has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection. |
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | Yes |
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 |
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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 | 53 |
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 |
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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
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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 | 10 |
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 | 0 |