E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment with three-class (NRTI, NNRTI, and PI) experienced HIV positive patients with HCV or HBV co-infection, with a minimum of 3-months duration for each class and have documented resistance to more than one PI. They must be TPV naïve, have at least two available active ARV drugs to construct a background regimen. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020192 |
E.1.2 | Term | HIV-1 |
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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 objective of this study is to assess the safety and efficacy of TPV/r (500 mg/200 mg BID) in ARV therapy experienced HIV-1 infected patients co-infected with HCV or HBV in the presence of an NRTI-based, resistance-driven optimized background regimen.
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E.2.2 | Secondary objectives of the trial |
The objective of the TDM pilot evaluation is to determine the potential utility of therapeutic drug monitoring in the use of TPV/r in co-infected patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. HIV-1 infected males or females ≥18 years of age. 2. Three-class (NRTI, NNRTI, and PI) treatment-experienced (a minimum of 3-months duration for each class) with resistance to more than one PI (on the screening resistance testing). Patients that are NNRTI-naïve patients but who have genotypically documented NNRTI-resistance mutations on past or screening resistance testing would be eligible. 3. Chronic hepatitis C Virus infection demonstrated by HCV-RNA positivity or, Chronic hepatitis B infection demonstrated by anti-HBc-IgG Antibody and HB Surface Antigen positivity. 4. The ARV study treatment regimen must consist of new TPV/r in combination with an OBR of 2-4 agents of the following: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or, where available, an Expanded Access Program (EAP) investigational agent (Section 3.3). In total, patients are to have an ARV study treatment regimen consisting of at least 3 agents (TPV/r and two OBRs).
The following considerations must be applied in construction of the OBR:
• At least one of the OBR agents must be new (defined as first time patient use). • If two N(t)RTIs are used for the OBR, at least one of the RTIs must be new to the patient with a “maximal response” on the Virco resistance analysis report. The other N(t)RTIs in the regimen may have either a “maximal or reduced response” on the Virco resistance analysis report. • If either new ENF and/or potentially approved new agents (e.g., raltegravir and maraviroc) are used for the OBR, the N(t)RTIs may have either a “maximal or reduced response” on the Virco resistance analysis report. Raltegravir and maraviroc may be accessed commercially if approved or through EAPs where available. • N(t)RTIs that are classified as having a “minimal or resistant response” on the Virco resistance analysis report may be used but will not count as one of the 2-4 active agents required to be in the OBR. • For patients who had previously taken lamivudine (3TC) or emtricitabine (FTC), neither of these drugs is considered as sensitive regardless of the genotype report. If previously taken, either 3TC or FTC may be included in the OBR but will not count as one of the 2-4 agents required to be in the OBR.
Patients co-infected with HBV already treated at screening with anti-HBV drugs which have also an anti-HIV activity (lamivudine, emtricitabine, tenofovir) should remain on these drugs during the trial. These drugs, however, will not be counted as active anti HIV drugs in the background regimen.
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E.4 | Principal exclusion criteria |
1. Prior tipranavir use 2. ARV medication naïve. 3. Genotypic resistance to TPV (defined as a TPV mutation score >7). 4. Decompensated liver disease, including presence or history of ascites, variceal bleeding, or hepatic encephalopathy or having ever been diagnosed as having hepatic insufficiency of Child Pugh class B or C. 5. Use of immunomodulatory drugs (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2) or antineoplastic agents within 30 days before study entry or during the trial. 6. Anticipated need for any interferon-based regimen in the 48 weeks following the study entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is treatment response at Week 48. Treatment response is a confirmed virologic response, defined as a viral load <50 copies/mL at two consecutive measurements at least 5 days apart, without death, premature discontinuation of the study drug or loss to follow up, or introduction of a new antiretroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background drug.
Occurrence of dose-limiting hepatotoxicity during the study. Dose-limiting hepatotoxicity is defined as Grade 4 ALT or AST elevation confirmed in 48h or any evocative symptoms or signs of hepatitis, if it not clearly attributable to another cause.
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Pilot evaluation of therapeutic drug monitoring; retrospective pharmacogenetic is optional |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 |
Randomisation for pilot evaluation of TDM |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | Information not present in EudraCT |
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 |
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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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The end of the trial is when the last patient will have his last visit (study completion visit which has to be planned 30 days after the week-48 visit). |
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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 | |
E.8.9.1 | In the Member State concerned months | 22 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 22 |