E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HCV Genotype 1 and HCV Genotype 1/HIV-1 co-infected subjects |
|
E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Virus Infection |
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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 | 20.0 |
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 |
|
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 show the non-inferiority of the SVR12 rates among mono-infected HCV GT1 DAA-naïve subjects (the percentage of subjects achieving a 12-week sustained virologic response, SVR12, [HCV RNA < LLOQ 12 weeks following therapy]) of 12 weeks of treatment with the combination regimen ABT 493/ABT-530 to the historical SVR rate established by current approved standard of care regimens for mono-infected HCV GT1 DAA-naïve subjects (ombitasvir/paritaprevir/ritonavir + dasabuvir ± RBV or SOF/LDV for 12 weeks);
● To show the non-inferiority in SVR12 rates among mono-infected HCV GT1 DAA-naïve subjects of the ABT-493/ABT-530 regimen for 8 weeks versus 12 weeks of treatment; and
● To assess the safety of 8 and 12 weeks of treatment with the combination regimen ABT-493/ABT-530. |
|
E.2.2 | Secondary objectives of the trial |
● The percentage of subjects with SVR12 among mono-infected HCV GT1 subjects;
● The percentage of subjects with SVR12 among all HCV GT1 subjects;
● The percentage of subjects with SVR12 among subjects with HCV GT1/HIV-1 co-infection;
● The percentage of subjects with SVR12 among prior SOF treatment experienced HCV GT1 subjects;
● The percentages of subjects with on-treatment virologic failure;
● The percentages of subjects with post-treatment relapse. |
|
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 |
- optional pharmacogenetic
- optional pharmacokinetic |
|
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age at time of screening.
2. Screening laboratory result indicating HCV GT1 infection.
3. Chronic HCV infection.
4. Subject must be HCV treatment-naïve (i.e., patient has never received a single dose of any approved or investigational regimen) or treatment-experienced (has failed prior IFN or pegIFN with or without RBV, or SOF plus RBV with or without pegIFN therapy).
5. Subjects must be non-cirrhotic.
Additional Inclusion Criteria for GT1 HCV/HIV-1 co-infected patients:
6. HIV-1 ART naïve with CD4 ≥ 500 cells/mm3 [or CD4+ % ≥29%] at Screening and plasma HIV-1 RNA <1,000 copies/mL at Screening and at least once during the 12 months prior to Screening.
Or
On a stable, qualifying HIV-1 ART regimen (Section 5.2.3.2) for at least 8 weeks prior to screening, with CD4 ≥ 200 cells/mm3 [or CD4+ % ≥14%] at Screening and plasma HIV-1 RNA <LLOQ at Screening and at least once during the 12 months prior to Screening. |
|
E.4 | Principal exclusion criteria |
1. History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs.
2. Female who is pregnant, planning to become pregnant during the study or breastfeeding; or male whose partner is pregnant or planning to become pregnant during the study.
3. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator.
4. Positive test result at Screening for hepatitis B surface antigen (HBsAg).
5. HCV genotype performed during screening indicating co-infection with more than one HCV genotype.
6. Chronic human immunodeficiency virus, type 2 (HIV-2) infection. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Efficacy of the 12-week treatment duration (Arm A): lower bound of the two-sided 95% confidence interval for the percentage of subjects in Arm A achieving SVR12 is greater than 91% among mono-infected HCV GT1 DAA-naive subjects.
2. Non-inferiority of the 8-week treatment duration (Arm B) to Arm A in SVR12 using a non-inferiority margin of 5% in the per protocol (PP) population among mono-infected HCV GT1 DAA-naïve subjects, as described below.
3. Non-inferiority of Arm B to Arm A in SVR12 using a non-inferiority margin of 5% among
mono-infected HCV GT1 DAA-naïve subjects. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks following the last dose of study drug |
|
E.5.2 | Secondary end point(s) |
● the percentage of subjects with SVR12 in the ITT-MS population (ITT mono-infected HCV GT1 subjects);
● the percentage of subjects with SVR12 in the ITT population;
● the percentage of subjects with SVR12 among subjects with HCV GT1/HIV-1 co-infection;
● the percentage of subjects with SVR12 among prior SOF-treatment experienced HCV GT1 subjects;
● the percentage of subjects with on-treatment virologic failure (defined as confirmed increase of > 1 log10 IU/mL above nadir during treatment, confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at the end of treatment with at least 6 weeks of treatment), and
● the percentage of subjects 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 who completed treatment as planned with HCV RNA < LLOQ at the end of treatment; excluding subjects who have been shown to be reinfectedwith further breakdown by relapse versus reinfection based on HCV population sequencing). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 weeks following the 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 |
Chile |
Israel |
Korea, Republic of |
Mexico |
New Zealand |
Puerto Rico |
Russian Federation |
Switzerland |
Taiwan |
United States |
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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
|
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |