E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
UK-427,857 is an antagonist of the human chemokine receptor, and is intended to help prevent the development and progression of AIDS in indivuduals HIV-1 positive. |
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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 | 10020180 |
E.1.2 | Term | HIV positive |
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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 confirm the hypothesis that UK-247,857 added to Optimised Background Therapy (OBT) provides an additional reduction in plasma HIV-1 RNA compared to OBT alone, as measured by the difference between each of the two UK-427,857 regimens versus the placebo regimen in the mean changes from baseline in plasma HIV-1 RNA at week 48. An interim analysis will be performed at week 24. |
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E.2.2 | Secondary objectives of the trial |
To compare the percentage of subjects with HIV-RNA less than 400 copies/mL and 5O copies/mL at week 24 and 48. To compare the percentage of subjects who achieve at least a 0.5 log10 and 1log10 reduction in HIV-RNA from baseline at week 24 and 48. To compare the time to loss of virological response through week 48. To compare the differences in the magnitude of changes in the CD4 and CD8 cell counts from baseline through week 24 and 48. To compare the Time Average Difference in log10 HIV-1 RNA at week 24 and 48. To assess HIV-1 genotype, phenotype and tropism at baseline and at the time of failure, and the association between baseline resistance and virological response. To assess the safety and the tolerability of the 2 UK-427,857 regimens versus placebo regimen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
HIV-1 RNA superior to or equal to 5000 copies/mL measured by Roche Amplicor HIV-1 monitor at screening visit. Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks. Documented genotypic or phenotypic resistance to 3 of 4 antiretroviral drug classes. A negative urine pregnancy test at the baseline visit prior to receiving the first dose of study medication for women child bearing protential. |
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E.4 | Principal exclusion criteria |
Patient requiring treatment with more than 6 antiretroviral agents (excluded low dose ritonavir). Prior treatment with UK-427,857 or another experimental HIV entry inhibitor for more than 14 days. Suspected or documented active, untreated HIV-1related opportunistic infection (OI) or other conditions requiring acute therapy (eg Hepatitis C virus infection) at the time of randomisation. X4- or dual/mixed-tropic virus detected by PhenoSense viral entry assay or repeated assay failure. Renal insuffiecency, increased bilirubin/AST/ALT. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to 48 weeks in HIV-1 RNA measured on a logarithmic (base 10) scale. An interim analysis will be performed at week 24. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | 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) | Yes |
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 | 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 | No |
E.8.2.3 | Other | No |
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 | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
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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End of Trial is defined as when Last Subject reaches 5 years from the first dose of blinded medication. |
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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 | 5 |
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 | 5 |
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 |