| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C, Genotype 1 |
| Epatite C Cronica, Genotipo 1 |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| 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 efficacy of telaprevir in combination with peginterferon alfa-2a (Peg-IFN-alfa-2a) and ribavirin (RBV) in treatment-naive subjects with genotype 1 chronic hepatitis C. |
| Dimostrare l'efficacia del telaprevir in combinazione con peginterferone alfa-2a (Peg-IFN-alfa-2a) e ribavirina (RBV) in soggetti naive affetti da epatite C cronica genotipo 1 |
|
| 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-naive subjects with genotype 1 chronic hepatitis C. |
| Valutare la sicurezza del telaprevir in combinazione con Peg-IFN-alfa-2a e RBV in soggetti naive affetti da epatite C cronica genotipo 1. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Male and female subjects, 18 to 70 years of age inclusive. - Genotype 1, chronic hepatitis C with detectable HCV RNA. Genotype will be confirmed at screening. Chronic disease is defined as one of the following: <Diagnosis of HCV >6 months before the screening period, or <History of a remote risk factor, or <Abnormal alanine aminotransferase (ALT) levels for >6 months before the screening period (Note, elevated ALT is not an inclusion criterion if one of the otehr criteria for chronic hepatitis C was met) - Aside from hepatitis C, judged to be in good health on the basis of medical history and physical examination (including vital signs and screening ECG), with any chronic medical conditions under stable medical control. - Seronegative for Hepatitis B surface antigen and Human Immunodeficiency Virus (HIV) 1 and 2. - Parameters for Absolute neutrophil count, platelet count, hemoglobin, uric acid and other hematology and clinical chemistry results within ranges specified in Section 9 of the protocol. - Documentation of a liver biopsy within 1 year (+/- 3 months) before the screening visit or agree to have a biopsy performed during screening. The 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. - Female and Male subjects and female partners of male subjects must consent to following contraception instructions detailed Protocol section 9. - Willing to refrain from the concomitant use of any medications, substances, or foods noted in section 10.11 of the Protocol. - Able to read and understand, and willingness to sign the informed consent and abide by study restrictions. |
| Male and female subjects, 18 to 70 years of age inclusive. - Genotype 1, chronic hepatitis C with detectable HCV RNA. Genotype will be confirmed at screening. Chronic disease is defined as one of the following: <Diagnosis of HCV >6 months before the screening period, or <History of a remote risk factor, or <Abnormal alanine aminotransferase (ALT) levels for >6 months before the screening period (Note, elevated ALT is not an inclusion criterion if one of the otehr criteria for chronic hepatitis C was met) - Aside from hepatitis C, judged to be in good health on the basis of medical history and physical examination (including vital signs and screening ECG), with any chronic medical conditions under stable medical control. - Seronegative for Hepatitis B surface antigen and Human Immunodeficiency Virus (HIV) 1 and 2. - Parameters for Absolute neutrophil count, platelet count, hemoglobin, uric acid and other hematology and clinical chemistry results within ranges specified in Section 9 of the protocol. - Documentation of a liver biopsy within 1 year (+/- 3 months) before the screening visit or agree to have a biopsy performed during screening. The 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. - Female and Male subjects and female partners of male subjects must consent to following contraception instructions detailed Protocol section 9. - Willing to refrain from the concomitant use of any medications, substances, or foods noted in section 10.11 of the Protocol. - Able to read and understand, and willingness to sign the informed consent and abide by study restrictions. |
|
| E.4 | Principal exclusion criteria |
| Previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C. - Any contraindications to Peg-IFN-alfa-2a or RBV therapy. - Decompensated liver disease. - Any other cause of significant liver disease in addition to hepatitis C, which may include, but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), or primary biliary cirrhosis. - Diagnosed or suspected hepatocellular carcinoma. - Use of prohibited medications identified in Section 10.11 within 14 days before day 1. - A history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subjects. This may include but is not limited to a history of relevant drug or food allergies, history of cardiovascular or central nervous system disease, history or presence of clinically significant illness, or history of mental illness that may affect compliance with study requirements. - History of organ transplant, with the exception of corneal transplants and skin grafts which are permissible. - History of hemophilia. - History of acute or chronic pancreatitis. - Alcohol abuse or excessive use (in the opinion of the investigator, as judged by medical history) in the last 12 months. - Active drug abuse in the last 12 months. - Participation in any investigational drug study within 90 days before drug administration, or participation in more than 2 drug studies in the last 12 months (exclusive of the current study), or participation in any concurrent study. - Hypersensitivity to tartrazine (yellow dye #5). - Women who are pregnant, planning to become pregnant, or breastfeeding, and male partners of women who are pregnant or planning to become pregnant. |
| Previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C. - Any contraindications to Peg-IFN-alfa-2a or RBV therapy. - Decompensated liver disease. - Any other cause of significant liver disease in addition to hepatitis C, which may include, but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), or primary biliary cirrhosis. - Diagnosed or suspected hepatocellular carcinoma. - Use of prohibited medications identified in Section 10.11 within 14 days before day 1. - A history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subjects. This may include but is not limited to a history of relevant drug or food allergies, history of cardiovascular or central nervous system disease, history or presence of clinically significant illness, or history of mental illness that may affect compliance with study requirements. - History of organ transplant, with the exception of corneal transplants and skin grafts which are permissible. - History of hemophilia. - History of acute or chronic pancreatitis. - Alcohol abuse or excessive use (in the opinion of the investigator, as judged by medical history) in the last 12 months. - Active drug abuse in the last 12 months. - Participation in any investigational drug study within 90 days before drug administration, or participation in more than 2 drug studies in the last 12 months (exclusive of the current study), or participation in any concurrent study. - Hypersensitivity to tartrazine (yellow dye #5). - Women who are pregnant, planning to become pregnant, or breastfeeding, and male partners of women who are pregnant or planning to become pregnant. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary endpoint: Proportion of subjects achieving sustained viral response (SVR), demonstrated by achieving undetectable hepatitis C virus (HCV) RNA 24 weeks after last planned dose of study treatment. Key secondary endpoint: Proportion of subjects who have undetectable HCV RNA at Week 72 (i.e., 24 weeks after the last planned dose for subjects receiving 48 weeks of study treatment, and 48 weeks after the last planned dose for subjects receiving 24 weeks of study treatment). Other secondary endpoints: - Proportion of subjects achieving RVR, demonstrated by achieving undetectable HCV RNA 4 weeks after starting study treatment. - Proportion of subjects who have early viral response (EVR, defined as >/= 2-log10 decrease in HCV RNA at Week 12 compared to baseline). - Proportion of subjects who have undetectable HCV RNA at the end of treatment (EOT). - Proportion of subjects who have undetectable HCV RNA 12 weeks after last planned dose of study treatment. - Proportion of subjects who complete treatment with undetectable HCV RNA, and subsequently relapse between EOT and SVR assessment. - Biochemical response including transaminase levels and noninvasive markers of fibrosis. - Total Fatigue Score from the Fatigue Severity Scale (FSS). - Adverse events, physical examination findings, and clinical laboratory, vital sign, and electrocardiogram (ECG) assessments Tertiary Endpoints: - Amino acid sequence of the HCV NS3 protease domain - Pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of telaprevir, VRT-127394, Peg-IFN-alfa-2a, and RBV - Patient reported outcomes including EQ-5D and assessment of work productivity. |
| Percentuale di soggetti che raggiungono una risposta virale sostenuta (SVR, sustained viral response), dimostrata dal raggiungimento dell'HCV RNA non rilevabile 24 settimane dopo l'ultima dose di trattamento prevista nello studio. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| HCV sequencing, gene expression profiling, HLA and CYP gene sequencing, plasma proteomics |
|
| 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 |
| All groups double-blinded to week 12. Group A unblinded after Week 24 if HCV RNA is detectable |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 30 |
| 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 | No |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 30 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 30 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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