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.1.2 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 are to assess the safety of ABT- 450/r/ABT-267 with and without ABT-333 coadministered with and without RBV for 12 and 24 weeks in HCV GT 1- or 4-infected subjects with HIV-1 coinfection and to evaluate the percentage of subjects achieving SVR12 (HCV RNA < lower limit of quantification [LLOQ] 12 weeks following treatment). These objectives will be assessed separately within each part of the study. For Part 1a, the 12- and 24-week treatment arms will be assessed separately; For Part 1b, the darunavir (DRV) QD and BID arms will be assessed separately as well as in combination; And for Part 2, the GT 1-infected subjects will be assessed separately from the GT 4-infected subjects, and the percentage of GT 1-infected subjects achieving SVR12 will be compared to a threshold based on the historical SVR12 rate of sofosbuvir (SOF) plus ribavirin (RBV). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess the percentage of subjects with on-treatment HCV virologic failure, the percentage of subjects with HCV virologic relapse, and the percentage of subjects with plasma HIV-1 viral suppression at the end of treatment and at Post-Treatment Week 12 within each part of the study; and to compare the SVR12 rates between the 12-week (Arm A) and 24-week (Arm B) treatment arms in Part 1a of the study and between the DRV QD (Arm C) and BID (Arm D) arms in Part 1b of the study |
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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 |
Both substudies are described in the M14-004 Protocol Amendment 4.02.01 (15 Apr 2016). Specific purposes of the optional pharmacogenetic and pharmacogenomic substudies include: •identifying genetic reasons why certain people respond differently to ABT-450/r/ABT-267 and ABT-333 (if applicable); •finding out more information about how ABT-450/r/ABT-267 and ABT-333 (if applicable) work; •finding out information needed for research, development, and regulatory approval for tests to predict response to ABT-450/r/ABT-267 and ABT-333 (if applicable). |
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E.3 | Principal inclusion criteria |
1. Male or female at least 18 years of age at the time of screening. 2. Chronic HCV infection defined as: Positive anti-HCV Ab at Screening, and HCV RNA > 1,000 IU/ml at screening. 3. Plasma HIV-1 RNA < 40 copies/mL during screening using Abbott RealTime HIV-1 assay. 4. On a stable, qualifying HIV-1 antiretroviral (ART) regimen for at least 8 weeks prior to screening. The HIV-1 ART regimen must include at least one of the following ARV agents: • Atazanavir (ATV) PO QD coadministered with ritonavir (RTV) PO QD • Darunavir (DRV) PO QD coadministered with ritonavir (RTV) PO QD (for all subjects in Part 1b and genotype 4 subjects in Part 2 only) • Raltegravir (RAL) PO BID • Dolutegravir (DTG) PO QD or PO BID (Part 2 only) |
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E.4 | Principal exclusion criteria |
1. Positive test result at screening for Hepatitis B surface antigen (HBsAg). 2. Evidence of HCV genotype other than GT 1 or GT 4 during screening. 3. Receipt of any other investigational or commercially available anti-HCV agents (e.g., telaprevir, boceprevir, simeprevir, daclatasvir and ledipasvir) with the exception of interferon, (including pegIFN), SOF and RBV. 4. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-450, ABT-267, ABT-333, ritonavir or RBV. 5. Chronic human immunodeficiency virus, type 2 (HIV-2) infection. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of subjects in the GT 1 Analysis Group in Part 2 achieving SVR12 (HCV RNA < LLOQ 12 weeks after the last actual dose of study drug) compared to the historical SVR12 rate for sofosbuvir plus RBV as reported in the PHOTON-1 study. The percentage of subjects achieving SVR12 will be calculated and a 2-sided 95% confidence interval (CI) of the percentage will be computed using the Wilson score method for the binomial proportion. The lower confidence bound of the 2-sided 95% Confidence Interval (LCB) for the percentage of subjects achieving SVR12 must exceed 74% to achieve non-inferiority. |
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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: 1. The percentage of Part 1a subjects achieving SVR12 in the 24-week treatment group compared to the 12-week treatment group using Fisher's exact test. 2. The percentage of subjects of Part 1b subjects achieving SVR12 in the DRV QD arm compared to the DRV BID arm using Fisher's exact test. 3. The percentage of Part 1b subjects achieving SVR12. 4. The percentages of Part 2 GT 1b cirrhotic subjects achieving SVR12 in Arm F (without RBV) compared to Arm G (with RBV). 5. The percentage of GT 4 subjects in Part 2 achieving SVR12 by arm and overall. 6. The percentage of subjects with on treatment HCV virologic failure during the Treatment Period for the 12-week and 24-week treatment arms in Part 1a, the DRV QD and BID arms as well as the set of all subjects in Part 1b, the GT 1 Analysis Group in Part 2, and the GT4 Analysis Group in Part 2 by arm and overall. 7. The percentage of subjects with HCV post-treatment relapse (analyses performed as described for secondary endpoint 7). 8. The percentage of subjects with plasma HIV-1 RNA suppression at end of treatment and Post Treatment Week 12 using the FDA Snapshot Algorithm (analyses performed as described for secondary endpoint 7). Comparison of the DRV QD and BID arms in Part 1b will be made using Fisher's exact test. For each of the secondary endpoints, the percentages (with 2-sided 95% confidence intervals using the Wilson score method for the binomial proportion) will be calculated. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment Day 1 to end of treatment (week 12 or week 24) 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 | 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) | 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 | 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 | No |
E.8.2.4 | Number of treatment arms in the trial | 12 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
European Union |
Mexico |
New Zealand |
Puerto Rico |
Russian Federation |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |