E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV infection (R5-tropism only) with previous therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10200172 |
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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 |
To evaluate antiviral efficacy of 2 doses of vicriviroc maleate compared to placebo in combination with a ritonavir-boosted protease inhibitor (PI) containing optimized antiretroviral therapy (ART) regimen in CCR5-tropic HIV infected individuals failing a standard ART regimen. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the dose–response relationship of the two dosages of vicriviroc maleate along with an optimized background ART regimen. • To evaluate the pharmacokinetic–pharmacodynamic (PK–PD) relationship of vicriviroc maleate through the use of PK–PD population analyses. • To evaluate clinical efficacy with respect to the following: • Time to occurrence of AIDS-defining clinical events. • Incidence of AIDS-defining clinical events. • Frequency of emergence of viral resistance to vicriviroc • Frequency of emergence of CXCR4-tropic virus • Frequency of emergence of CXCR4-tropic virus with concomitant decline in CD4 count by more than or equal to 50% below baseline • Frequencies of AEs and clinically significant abnormalities in ECGs, laboratory findings, or CNS findings.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult subjects with documented HIV infection with R5-only tropism. • Prior therapy for at least 3 months with at least 3 classes of currently marketed (US FDA-approved) antiretroviral agents (NRTIs, NNRTIs, PIs, or fusion inhibitors) at any time prior to screening. • HIV RNA level of at least 1000 copies/mL on a stable ART regimen for at least 6 weeks • At least 1 genotypically documented resistance mutation to a reverse transcriptase (RT) inhibitor and at least 1 primary resistance mutation to a PI • Acceptable hematologic, renal and hepatic laboratory parameters • QTc internal less than 470 msec (female) and less than 450 msec male
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E.4 | Principal exclusion criteria |
• Detectable X4 or R5/X4 virus • History of recurrent seizure of CNS condition that may predispose the subject to seizure • Active AIDS defining opportunistic infection • Prior history of malignancy (with the exceptions of cutaneous Kaposi's sarcoma that resolved with HAART but without systemic anticancer treatment); or prior receipt of cytotoxic cancer chemotherapy that may increase the risk of malignancy • Known liver cirrhosis, or clinical symptoms, signs or laboratory abnormalities consistent with cirrhosis
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is the log10 change from baseline in HIV RNA at 48 weeks. Key secondary endpoints are: Proportion of subjects with at least a 1.0 log10 change from baseline HIV RNA at 48 weeks Proportion of subjects with HIV RNA <400 copies/mL at 48 weeks Time to virologic failure, defined as the time from randomization to either: - failure to experience HIV RNA decline of at least 0.5 log10 at 4 weeks after baseline, in which case time will be set to 0, OR - rebound of HIV RNA to within 0.5 log10 of baseline at any time after maximal suppression Either event of virologic failure must be confirmed on a repeat test
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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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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 | 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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |