E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus Infection
Human Immunodeficiency Virus Infection
Chronic Hepatitis C
Compensated Cirrhosis and Non-cirrhotics |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Virus Infection
Human Immunodeficiency Virus Infection |
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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 objectives of this study are to are to compare the SVR12 rates (12-week sustained virologic response, SVR12 [HCV RNA < LLOQ 12 weeks following therapy]) of 8 or 12 weeks of treatment with ABT-493/ABT-530 combination in HCV genotype 1 – 6 infected subjects with HIV-1 co-infection to a pre-defined threshold, based on the historical SVR12 rate of the current standard of care (i.e., sofosbuvir/ledipasvir for 12 weeks or grazoprevir/elbasvir for 12 weeks) and to assess the safety of treatment with the combination regimen ABT-493/ABT-530 for 8 or 12 weeks in HCV genotype 1 – 6 infected subjects with HIV-1 co-infection. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess:
● The percentages of subjects with on-treatment HCV virologic failure;
● The percentages of subjects with post-treatment HCV relapse.
Additional objectives are:
● To estimate the pharmacokinetics of ABT-493 and ABT-530.
● To evaluate the percentage of HIV-1/HCV co-infected participants on stable ART who maintain HIV RNA suppression at the end of DAA treatment and at 12 week post DAA treatment.
● To evaluate the emergence of HCV resistance-associated variants among the participants who developed HCV virologic failure.
● To evaluate the emergence of HIV drug resistance-associated variants among the participants who developed HIV virologic failure. |
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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 |
The Pharmacogenetic Substudy is described in the M14-730 Protocol Amendment 3 (12 July 2016).
Specific purposes of the optional pharmacogenetic sub-study include:
● To find out why some patients with HCV respond better or worse to ABT-493 and ABT-530 or drugs of the same or similar class
● To possibly find out how HCV and related conditions develop and progress and how they can be diagnosed, monitored or treated
● To possibly develop tests that identify which patients are likely to have specific diseases, respond to ABT-493 and ABT-530 or drugs of the same or similar class, or to predict the progression of HCV
● To possibly develop new therapies, research methods or technologies. |
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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-, 2-, 3-, 4-, 5-, or 6-infection.
3. Subject has positive anti-HCV Ab and plasma HCV RNA viral load ≥ 1000 IU/mL at Screening Visit.
4. Subjects must be HCV treatment-naïve (i.e., subject has not received a single dose of any approved or investigational anti-HCV medication) or HCV treatment-experienced (subject has failed prior IFN or pegIFN with or without RBV, or SOF plus RBV with or without pegIFN). GT3 subjects must be HCV treatment-naïve. Previous HCV treatment must have been completed ≥ 2 months prior to Screening.
5. Subjects naïve to ART must have CD4+ count ≥ 500 cells/mm3 (or CD4+ % ≥ 29%) at Screening; or
Subjects on a stable ART regimen must have the following:
• CD4+ count ≥ 200 cells/mm3 (or CD4+ % ≥ 14%) at Screening; and
• Plasma HIV-1 RNA below LLOQ at Screening and at least once during
the 12 months prior to Screening.
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E.4 | Principal exclusion criteria |
1. 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.
2. Positive test result at Screening for hepatitis B surface antigen (HBsAg).
3. Positive Human Immunodeficiency virus, type 2 (HIV-2) Ab at Screening.
4. Receipt of any other investigational or commercially available direct acting anti-HCV agents other than sofosbuvir (e.g., telaprevir, boceprevir, simeprevir, paritaprevir, grazoprevir, daclatasvir, ledipasvir, ombitasvir, elbasvir or dasabuvir).
5. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-493/ABT-530.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) in the ITT population |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks after the last dose of study drug |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
● The percentage of subjects with on-treatment HCV 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),
● The percentage of subjects with post-treatment HCV 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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Day 1 to end of treatment and end of treatment to 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 | No |
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.8.3 |
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 | 14 |
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 |
Belarus |
Puerto Rico |
Russian Federation |
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
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |