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.1.3 | 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 of this study is to assess the efficacy (the percentage of subjects achieving a 12-week sustained virologic response, SVR12 [HCV ribonucleic acid {RNA} < lower limit of quantification {LLOQ} 12 weeks following treatment]) of coformulated ombitasvir/paritaprevir/ritonavir and dasabuvir for 8 weeks in treatment-naïve adults with HCV genotype 1b infection without cirrhosis. |
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E.2.2 | Secondary objectives of the trial |
• Secondary objectives are to assess the percentage of subjects with virologic failure during treatment, the percentage of subjects with virologic relapse post-treatment, and the percentage of female subjects with SVR12 and the percentage of subjects with low baseline viral load (HCV RNA < 6,000,000 IU/mL) with SVR12 in previously untreated adults with genotype 1b HCV infection. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female at least 18 years of age at time of Screening.
2. HCV infection at Screening defined as: Positive for anti-HCV antibody (Ab) at Screening and HCV RNA > 1,000 IU/mL at Screening
3. Screening laboratory result indicating HCV genotype 1b infection only
4. Subject has never received commercial or investigational anti-HCV agents for hepatitis C infection (treatment-naïve subject).
5. Absence of cirrhosis, as documented by meeting one of the following criteria (per local standard practice):
• A liver biopsy within 12 months prior to or during screening demonstrating the absence of cirrhosis, e.g., a METAVIR Score of 3 or less, Ishak score of 4 or less;
• A FibroScan performed within 3 months prior to or during screening with a score of < 12.5 kPa; or
• A screening FibroTest score of ≤ 0.72 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 2 (Subjects with a screening FibroTest result that is ≤ 0.72 and an APRI > 2, or a FibroTest result that is > 0.72 and an APRI ≤ 2 must have a FibroScan or liver biopsy performed during screening to document absence of cirrhosis. These subjects will be allowed to enroll only with approval of the AbbVie Scientific Director).
If more than one method is used to determine the presence or absence of cirrhosis, the results of a liver biopsy will take precedence over FibroScan and FibroTest and the results of FibroScan will take precedence over FibroTest.
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E.4 | Principal exclusion criteria |
1. Evidence of HCV genotype or subtype other than GT1b during screening, including the presence of GT1b with another genotype or GT1 subtype.
2. Positive test result for Hepatitis B surface antigen (HbsAg) or confirmed positive anti-HIV antibody (HIV Ab) (test).
3. Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices or prior biopsy showing cirrhosis.
4. Screening laboratory analyses showing any of the following abnormal laboratory results:
• Calculated creatinine clearance (using Cockcroft-Gault method) < 30 mL/min
• Albumin < 3.5 g/dL
• Hemoglobin < 10 g/dL
• Platelets < 120,000 cells per mm3
• Total bilirubin ≥ 3.0 mg/dL
• International normalized ratio (INR) > 1.5. Subjects with a known inherited blood disorder and INR > 1.5 may be enrolled with permission of the AbbVie Scientific Director.
5. Clinically significant abnormalities or co-morbidities, other than HCV infection that make the subject an unsuitable candidate for this study or to receive ombitasvir/paritaprevir/ritonavir or dasabuvir in the opinion of the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is number and percentage of ITT subjects with SVR12 (HCV RNA < LLOQ 12 weeks after the last dose of study drugs). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after the last subject last dose |
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E.5.2 | Secondary end point(s) |
1. The percentage of subjects with on-treatment virologic failure, defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment, or confirmed increase of at least 1 log10 IU/mL from nadir during treatment, failure to suppress during treatment (all on-treatment values of HCV RNA ≥ LLOQ) among subjects with at least 6 weeks (active study drug duration ≥ 36 days) of treatment;
2. The percentage of subjects with post-treatment relapse, defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last dose of study drug (up to and including the SVR12 assessment time point) among subjects completing treatment and with HCV RNA < LLOQ at the end of treatment.
3. The percentage of female subjects with SVR12.
4. The percentage of subjects with baseline HCV RNA < 6,000,000 IU/mL with SVR12.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 weeks after the last subject last dose |
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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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Australia |
Canada |
France |
Germany |
Israel |
Italy |
Spain |
United Kingdom |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 10 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 10 |