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 | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The objective of this Amendment is to permit the collection and storage of blood samples for use
in future exploratory pharmacogenetic research. Bristol-Myers Squibb will use DNA obtained
from the blood sample and health information collected from the main clinical trial, AI438047 to
study the association between genetic variation and drug response. Bristol-Myers Squibb may
also use the DNA to study the causes and further progression of HIV Samples from this study
may also be used in conjunction with pharmacogenetic research results from other clinical
studies to accomplish this objective. |
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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
| 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 | 8 |
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 |