E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
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 purpose of this study is to determine whether the BMS Attachment Inhibitor (BMS-663068) effective in the treatment of heavily treatment experienced HIV-1 patients with multi-drug resistance |
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E.2.2 | Secondary objectives of the trial |
- The proportion of subjects with HIV-1 RNA decreases from baseline that exceed 0.5 log10c/mL and 1 log10 c/mL is determined
-The durability of response (HIV-1 RNA < 40 c/mL) at Week 24 of OBT is assessed using the FDA snapshot algorithm
-The frequency of SAEs, AEs leading to discontinuation, and Grade 3-4 laboratory abnormalities during OBT are tabulated from Case Report Forms (CRFs) and laboratory data
-Disease progression during OBT is assessed is assessed using the occurrence of new AIDS defining
events (CDC Class C events) or death as tabulated from CRFs
-Drug resistance is assessed
-The changes in CD4+ T-cells counts and percentages, for BMS-663068 and placebo are determined using the mean changes from baseline (Day 1) to Day 8.
-The changes from baseline in HIV-1 RNA, CD4+ cell counts, and percentage of CD4+ T-cells, for BMS-663068 when given with OBT, are assessed using laboratory results collected through Week 24
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and non-pregnant women with chronic HIV-1 infection
• Antiretroviral-experienced with documented historical or baseline resistance, intolerability, and/or contraindications to antiretrovirals in at least three classes
• Failing current antiretroviral regimen with a confirmed plasma HIV-1 RNA ≥ 400 c/mL (first value from Investigator, second from Screening labs)
• Must have ≤ 2 classes with at least 1 but no more than 2 fully-active antiretrovirals remaining which can be effectively combined to form a viable new regimen, based on current and/or documented historical resistance testing and tolerability and safety
• Able to receive ≥ 1 fully active approved antiretroviral as part of the OBT from Day 9 onwards in the Randomized Cohort
• Subjects without any remaining fully active approved antiretroviral may be enrolled in the Non-Randomized Cohort
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E.4 | Principal exclusion criteria |
• Chronic untreated HBV (however, patients with chronic treated HBV are eligible)
• HIV-2 infection
• ALT or AST > 7 x ULN
• Alkaline Phosphatase > 5 x ULN
• Bilirubin ≥ 1.5 x ULN (unless subject is currently on atazanavir and has predominantly unconjugated hyperbilirubinemia)
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E.5 End points |
E.5.1 | Primary end point(s) |
The efficacy of BMS-663068, relative to placebo, is assessed using the mean change in log10 HIV-1 RNA from
Day 1(baseline) to Day 8 as determined by maximum likelihood methods.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At day 8 follow the start of Blinded BMS-663068 (or Placebo) + optimized background therapy (OBT) |
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E.5.2 | Secondary end point(s) |
- The proportion of subjects with HIV-1 RNA decreases from baseline that exceed 0.5 log10c/mL and 1 log10 c/mL is determined by comparing each subject’s HIV-1 RNA baseline measurement to their Day 8 measurement. Subjects without data at Day 8 are classified as failures
-The durability of response (HIV-1 RNA < 40 c/mL) at Week 24 of OBT is assessed using the FDA snapshot algorithm
-The frequency of SAEs, AEs leading to discontinuation, and Grade 3-4 laboratory abnormalities during OBT are tabulated from Case Report Forms (CRFs) and laboratory data
-Disease progression during OBT is assessed is assessed using the occurrence of new AIDS defining events (CDC Class C events) or death as tabulated from CRFs
-Drug resistance is assessed through phenotypic and genotypic resistance testing of isolates from subjects identified as meeting the criteria for virologic failure
-The changes in CD4+ T-cells counts and percentages, for BMS-663068 and placebo are determined using the mean changes from baseline (Day 1) to Day 8.
-The changes from baseline in HIV-1 RNA, CD4+ cell counts, and percentage of CD4+ T-cells, for BMS-663068 when given with OBT, are assessed using laboratory results collected through Week 24
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 |
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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 | 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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
Colombia |
Denmark |
France |
Germany |
Greece |
Ireland |
Italy |
Mexico |
Netherlands |
Norway |
Peru |
Poland |
Portugal |
Puerto Rico |
Romania |
Russian Federation |
South Africa |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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Last follow-up visit of the last subject |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 15 |