| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hepatitis C Virus Infection |
|
| 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 | 10019752 |
| E.1.2 | Term | Hepatitis C virus (HCV) |
|
| 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 estimate the difference in SVR rates between T12/PR24 and T12/PR48 treatment regimens in subjects who achieve eRVR. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety of telaprevir in combination with Peg-IFN-alfa-2a and RBV in treatment-naïve subjects with genotype 1 chronic hepatitis C. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. May not have received any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C
2. Male and female subjects, 18 to 70 years of age, inclusive
3. Genotype 1, chronic hepatitis C with detectable HCV RNA. Genotype must be confirmed during screening. Confirmation that the disease is chronic (as opposed to acute disease of less than 6 months duration) must be by at least 1 of the following criteria:
• Diagnosis of HCV >6 months before the screening visit
• Abnormal alanine aminotransferase (ALT) levels for >6 months before the screening period (Note: ALT does not have to be elevated to be eligible for the study, but history of elevated ALT can indicate duration of the infection).
4. Screening laboratory values within acceptable ranges
5. Subject must have documentation of a liver biopsy within 1 year before the screening visit, or the subject must agree to have a biopsy performed within the screening period. Liver biopsy must show evidence of hepatitis (demonstrated by inflammation and/or fibrosis). If a biopsy more than 1 year prior to screening has already demonstrated histological cirrhosis, the biopsy does not need to be repeated if this biopsy report can be provided.
6. Subjects (or their female partners) must not be pregnant, or planning to become pregnant throughout the study dosing period and through 6 months post-dosing for female study subjects, 7 months post-dosing for female partners of male study subjects; or they must be permanently sterile or otherwise of non childbearing potential. They must also not be breastfeeding. If of child-bearing potential, female subjects must agree to use 2 effective methods of contraception from screening through 6 months after the last dose of RBV. Male subjects who have a female partner of childbearing potential must agree to use 2 effective methods of contraception from Screening through 7 months after the last dose of RBV unless vasectomized.
7. Willing and able to refrain from the concomitant use of any medications, substances, or foods noted in protocol Section 10.12, from 14 days prior to the first day of dosing through the end of treatment.
8. Able to read and understand, and willing to sign the informed consent form and abide by the study restrictions. |
|
| E.4 | Principal exclusion criteria |
1. Subject has any contraindications to Peg IFN alfa 2a or RBV therapy, including but not limited to any of the following:
• Hypersensitivity to any component of Peg-IFN –alfa-2a or RBV
• Hemoglobinopathies (including thalassemia major, sickle-cell disease)
• History or other 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 ≤ 50mL/min at screening
• Antinuclear antibody (ANA) titer 1:640 at screening and/or evidence of autoimmune hepatitis on liver biopsy
2. Evidence of hepatic decompensation in cirrhotic subjects: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, and/or screening laboratory results of any of the following:
• International Normalized Ratio (INR) of 1.5
• Serum albumin <3.3 g/dL
• Serum total bilirubin >1.8 times the upper limit of normal (ULN), unless history of Gilbert’s disease
3. Any other cause of significant liver disease in addition to hepatitis C, which may include, but is not limited to malignancy with hepatic involvement, hepatitis B, drug or alcohol related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, nonalcoholic steatohepatitis (NASH), or primary biliary cirrhosis
4. Diagnosed or suspected hepatocellular carcinoma as evidenced by screening alfa fetoprotein (AFP) of ≥ 50 ng/mL. If AFP is ≥ 50 ng/mL, absence of a mass must be demonstrated by ultrasound within two months prior to the screening period
5. Active malignant disease or history of malignant disease within 5 previous years (with the exception of treated basal cell carcinoma)
6. Pre-existing psychiatric condition that could interfere with the subject’s participation in and completion of the study, 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. History of significant craniocerebral trauma or active seizure disorders requiring medication
8. History of organ transplant, with the exception of corneal transplants and skin grafts
9. Medical condition that requires frequent or prolonged use of systemic corticosteroids (e.g., severe asthma, severe arthritis or autoimmune conditions, organ transplantation, adrenal insufficiency, etc.)
10. Autoimmune-mediated disease (e.g., Crohn’s disease, ulcerative colitis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis)
11. History of acute pancreatitis within 5 years prior to the screening visit
12. History or other evidence of severe retinopathy or clinically significant ophthalmological disorder due to diabetes mellitus or hypertension. For subjects with a history of hypertension or diabetes, written clearance from an ophthalmologist has to be obtained before the start of treatment
13. History or other clinical evidence of chronic pulmonary disease associated with functional impairment
14. History of hemophilia
15. Evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis
16. Currently abusing illicit drugs (narcotics or other controlled substances) or alcohol, or has a history of illicit substance or alcohol abuse within 2 years prior to the screening visit. Subjects who have a history of abuse of illicit drugs or alcohol should have had no incidents of abuse within the 2 years prior to the screening visit. Patients with a history of abuse of narcotics or other controlled substances should be known by the investigative site and considered to be a good candidate for this clinical research study. Patients treated with methadone should be on a stable methadone program for at least 6 months prior to screening.
17. Participation in any investigational drug study within 90 days before study drug dosing, or participation in more than 2 drug studies in the 12 months before study drug dosing, or participation in any concurrent research study including non-drug studies from screening until the end of the subject’s participation in this study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of randomized subjects achieving sustained viral response (SVR), demonstrated by achieving undetectable HCV RNA 24 weeks after last dose of study treatment |
|
| 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 | No |
| 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 | 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 | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| HCV RNA results will be double-blinded up to Week 24 |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Continuing peginterferon alfa-2a and ribavirin therapy to Week 48 |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 7 |
| 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 | 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| 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 | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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