| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic Hepatitis C Infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10008909 |
| E.1.2 | Term | Chronic hepatitis |
| E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
|
| 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 assess the safety and efficacy (the percentage of subjects with HCV RNA <LLOG 12 weeks after the last actual dose of study drug (SVR12 actual)) of ABT-450/r and ABT-267 among HCV subjects as specified in the Substudies 1 and 2 objectives below. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the rates of SVR24 actual (HCV RNA <LL0Q 24 weeks after the last actual dose of study drug), on-treatment virologic failure, and post-treatment relapse among all treated subjects. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Substudy 1 (Non-cirrhotic subjects)
Main objective Substudy 1:
The primary objective is to assess the safety and efficacy of ABT-450/r and ABT-267 with or without RBV among treatment-naive and pegIFN/RBV treatment experienced HCV genotype 1b and 4 infected subjects without cirrhosis
Substudy 2 (Subjects with compensated cirrhosis)
Main objective Substudy 2:
The primary objective is to assess the safety and efficacy of ABT-450/r and ABT-267 among treatment-naive and pegIFN/RBV treatment-experienced HCV genotype 1b-infected subjects with compensated cirrhosis
|
|
| E.3 | Principal inclusion criteria |
1.Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
2.Subjects must meet one of the following categories:
• Treatment-naïve: Subject has never received antiviral treatment for hepatitis C infection (Subjects with HCV genotype 1b infection with or without cirrhosis or HCV genotype 4 infection; Groups 1, 2, 4, and 7); OR•Prior null responders: Subject has documentation that they previously received pegIFN/RBV for at least 10 weeks and failed to achieve a 2 log10 IU/mL HCV RNA decrease at Week 12 (Week 10 to Week 16) (Subjects with HCV genotype 1b infection with or without cirrhosis or HCV genotype 4 infection; Groups 3, 5, 6, and 8); OR•Partial responder: Received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved ≥ 2 log10 reduction in HCV RNA at Week 12 (Weeks 10 – 16), but failed to achieve HCV RNA undetectable at the end of treatment (Subjects with HCV genotype 1b infection and compensated cirrhosis or HCV genotype 4 infection; Group 5, 6, and 8); OR•Relapser: Received at least 36 weeks of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 52 weeks of treatment follow-up (Subjects with HCV genotype 1b infection and compensated cirrhosis or HCV genotype 4 infection; Group 5, 6, and 8).
3.Body mass index (BMI) is ≥ 18 to < 38 kg/m2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
4.Chronic HCV genotype 1b or 4-infection for at least 6 months prior to study screening.
5.Subject has plasma HCV RNA level > 10,000 IU/mL at Screening.
Main Inclusion for Substudy 1:
1. Per local standard practice, documented results of:
- Liver biopsy within 24 months prior to screening or during screening demonstrating the absence of cirrhosis.
- Only in the absence of a biopsy within the 24 months prior to screening or during screening:
- a screening FibroTest score of ≤ 0.72 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 2; or
- a screening FibroScan® result of < 9.6 kPa. Subjects with a non qualifying FibroTest/APRI or FibroScan result may only be enrolled if they have a qualifying liver biopsy performed during screening.
Main Inclusion for Substudy 2:
1. Per local standard practice, documentation of cirrhosis by one of the following methods:
- Previous histologic diagnosis on liver biopsy, e.g., Metavir Score of > 3 (including 3/4 or 3 – 4), Ishak score of > 4 or,
- FibroScan score ≥ 14.6 kPa within 6 months of Screening or during the Screening Period (FibroScan must be locally approved to qualify for entrance criteria). Subjects with a non-qualifying FibroScan result may only be enrolled if they have a qualifying liver biopsy performed during screening.
2. Compensated cirrhosis defined as Child-Pugh score of ≤ 6 at Screening. |
|
| E.4 | Principal exclusion criteria |
1.History of severe, life-threatening or other significant sensitivity to any drug.
2.Females who are pregnant or breastfeeding.
3.Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
4.Positive test result for hepatitis B surface antigen or anti-HIV antibodies.
5.Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis.
Main Exclusion for Substudy 1:
1. Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis.
2. Absolute neutrophil count (ANC) < 1500 cells/µL (< 1200 cells/µL for subjects of black/African descent)
Main Exclusion for Substudy 2:
1. Any current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation such as ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the percentage of subjects with SVR12 actual (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug)in each treatment group. The primary comparison will be between Groups 2 and 3. Additional comparisons between Groups 1 and 4 and between Groups 5 and 6 (if both are enrolled) will be performed. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 12 weeks after last dose of study drug |
|
| E.5.2 | Secondary end point(s) |
● The percentage of subjects with SVR24 actual (HCV RNA < LLOQ 24 weeks after the last actual dose of study drug),
● The percentage of subjects with on-treatment virologic failure
● The percentage of subjects with post-treatment relapse |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 24 weeks after last dose of study drug. |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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 | 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 8 |
| 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 | 25 |
| 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 | No |
| 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 |
| France |
| Hungary |
| Italy |
| Poland |
| Puerto Rico |
| Romania |
| Spain |
| Turkey |
| United States |
|
| 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 | 25 |
| 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 | 25 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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