E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
The primary objectives of this study in HCV genotype 4-infected subjects with compensated cirrhosis receiving treatment with co-formulated ombitasvir/ABT-450/ritonavir co-administered with RBV for 12, 16, or 24 weeks are to assess the safety and to compare the percentage of subjects, who are either treatment-naïve or who have previously received only IFN/RBV treatment for HCV, achieving a 12-week sustained virologic response, SVR12 (HCV ribonucleic acid [RNA] < lower limit of quantification [LLOQ] 12 weeks following treatment), to a clinically relevant threshold (based on SVR rates for HCV genotype 4-infected subjects treated with pegIFN/RBV). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess the following in HCV genotype 4-infected subjects with compensated cirrhosis who are either treatment-naïve or who have previously received only IFN/RBV treatment for HCV:
To compare the SVR12 following 12 weeks of treatment (Arm A) to the SVR12 following 16 weeks of treatment (Arm B),
To compare the SVR12 following 16 weeks of treatment (Arm B) to the SVR12 following 24 weeks of treatment (Arm C),
To assess the percentage of subjects with on-treatment virologic failure during 12, 16, or 24 weeks of treatment (each of Arms A, B and C), and
To assess the percentage of subjects experiencing post-treatment relapse within 12 weeks following the end of either 12, 16, or 24 weeks of treatment (Relapse12) (each of Arms A, B and C). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Arms A, B and C:
-Subjects must meet one of the following:
* Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR
* Treatment Experienced (Prior null responders, Partial responders or Relapsers to IFN/RBV);
- Chronic HCV genotype 4 infection with cirrhosis.
- Subject has plasma HCV RNA level > 1,000 IU/mL at Screening
Arm D:
-Subject must have prior treatment experience with SOF/pegIFN/RBV or SOF/RBV and meet one of the following categories:
* Prior SOF breakthrough/non-responder: HCV RNA detectable at the end of treatment with SOF/pegIFN/RBV or SOF/RBV;
* Prior SOF relapser: achieved HCV RNA undetectable at end of a prior treatment course SOF/pegIFN/RBV or SOF/RBV, but HCV RNA was detectable within 52 weeks following completion of therapy. |
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E.4 | Principal exclusion criteria |
-Positive test result at Screening for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab)
-Current enrollment in another interventional clinical study, previous enrollment in this study, or previous use of any protease inhibitor, non-nucleoside polymerase inhibitor, or NS5a inhibitor, either investigational or commercially available (including previous exposure to ABT-450 or ombitasvir), or receipt of any investigational product within 6 weeks prior to study drug administration. Prior use of any direct-acting antiviral will not be allowed, except for Arm D where prior experience with the nucleoside polymerase inhibitor, sofosbuvir with pegIFN/RBV or RBV, is required
-Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites, variceal bleeding, or hepatic encephalopathy
-Confirmed presence of hepatocellular carcinoma
-Any cause of liver disease other than chronic HCV infection
-Abnormal laboratory tests. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of subjects with SVR12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after last dose of study drugs |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
a)The percentage of subjects with SVR12 in Arm B compared to Arm A;
b)The percentage of subjects with SVR12 in Arm C compared to Arm B;
c)The percentage of subjects in Arms A, B, and C with on-treatment virologic failure during the Treatment Period (defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment or confirmed HCV RNA ≥ LLOQ at the end of treatment);
d)The percentage of subjects in Arms A, B, and C with post-treatment relapse (defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drug among subjects completing treatment and with HCV RNA < LLOQ at the end of treatment). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) 12 weeks after last dose of study drug;
b) 12 weeks after last dose of study drug;
c) up to 24 weeks after first dose of study drug
d) within 12 weeks after the last dose of study drug |
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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 | 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 | Yes |
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 |
Threshold based on historical SVR rates |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Canada |
European Union |
United States |
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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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |