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.1.3 | 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 |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Provide a signed and dated written informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. 2. Men or women at least 16 years of age (or minimum age as deterined by local regulattory authorities or as legal requirements dictate). 3. HIV-1 RNA superior to or equal to 5000 copies/mL measured by Roche Amplicor HIV-1 monitor at screening visit. 4. Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks. 5. Documented genotypic or phenotypic resistance to 3 of the 4 antiretroviral drug classes or antiretrovial-class experience superior to or equal to 6 months (sequential or cumulative) with at least three of the following: a. One nucleoside or nucleotide reverse transcriptase inhibitor; b. One non-nucleoside reverse transcriptase inhibitor, c. Two protease inhibitors (excluding low-dose ritonavir); d. Enfuvirtide. 6. Be willing to initiate and remain on randomized treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure. 7. A negative urine pregnancy test at the baseline visit prior to receiving the first dose of study medication for women child bearing protential. 8. Effective barrier contraception for WOCBP and males. In addition, WOCBP must use another acceptable method of contraception for the duration of the study. Acceptable contraception includes, but is not limited to, oral, implanted or injected hormone therapy and intrauterine devices.
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the trial: 1. Patient requiring treatment with more than 6 antiretroviral agents (excluded low dose ritonavir). 2. Prior treatment with UK-427,857 or another experimental HIV entry inhibitor for more than 14 days 3. Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow-up 4. Lactating women, or planned pregnancy during the trial period 5. Suspected or documented active, untreated HIV-1 related opportunistic infection (OI) or other conditions requiring acute therapy (eg Hepatitis C virus infection) at the time of randomisation. 6. Treatment for an active OI, or unexplained temperature >38,5°C for 7 consecutive days, within 30 days prior to randomization 7. Malignancy requiring parenteral chemotherapy that must be continued for the duration of the trial 8. Initiating therapy with potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 60 days prior to randomization, or the expected need for such therapy during the study period 9. Documented or suspected acute hepatitis or pancreatitis within 30 days prior to randomization 10. Renal insufficiency defined as a serum creatinine greater than 3 times the ULN 11. Total bilirubin, greater than 2.5 times the ULN 12. AST or ALT greater than 5 times the ULN 13. Cirrhosis of the liver 14. Absolute neutrophil count inferior to or equal 750 cells/mm³ 15. Platelet count inferior to or equal 50.000 cells/mm³ 16. Hemoglobin inferior to or equal 7g/dL 17. Clinically significant malabsorption syndrome 18. Inability to tolerate oral medication 19. X4- or dual/mixed-tropic virus detected by PhenoSense viral entry assay or repeated assay failure. 20. Concomitant therapy with other investigational agents 21 Contraindicated medications (eg, immunomodulators for the treatment of HIV-1 infection; interferon for the ongoing treatment of hepatitis C infection is permitted) being tyken by the subject at the time of randomization that must be continued during the study period 22. Any safety, behavioral, clinical or administrative reasons that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
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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 | 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) | 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 | 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 | 28 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |