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 | 17.1 |
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 |
El objetivo de este estudio es determinar si el inhibidor del acoplamiento de BMS (BMS-663068) es eficaz en pacientes con fracasos múltiples al tratamiento antirretroviral, infectados por VIH 1 resistente a múltiples fármacos |
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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 |
- Proporción de sujetos con descensos del ARN del VIH 1 respecto al basal que superen 0,5 log10 c/ml y 1 log10 c/ml - Durabilidad de la respuesta (ARN del VIH 1 < 40 c/ml) del TBO en la semana 24 utilizando el algoritmo snapshot de la FDA - Frecuencia de AAG, AA que conducen a suspensión y anomalías de laboratorio de grado 3-4 durante el TBO según los cuadernos de recogida de datos (CRD) y datos de laboratorio - Progresión de la enfermedad durante el TBO según la aparición de nuevos eventos definitorios de SIDA (clase C de los CDC) o muerte a partir de los CRD - Resistencias al fármaco - Cambios en los recuentos y porcentajes de linfocitos T CD4+, para BMS-663068 y placebo se determinan usando los cambios medios desde el basal (día 1) hasta el día 8. - Los cambios respecto al momento basal en el ARN del VIH 1, los recuentos y el porcentaje de linfocitos T CD4+ para BMS-663068 cuando se administra con TBO, se evalúan usando resultados de laboratorio recogidos hasta la semana 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, AI438-047 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. |
El objetivo de esta enmienda es permitir la recogida y conservación de muestras de sangre para utilizar en futuras investigaciones exploratorias de farmacogenética. Bristol-Myers Squibb utilizará el ADN obtenido de las muestras de sangre y la información de salud recogida del estudio principal AI438-047 para estudiar la asociación entre la variación genética y la respuesta al fármaco. Bristol-Myers Squibb puede utilizar también el ADN para estudiar las causas de progresión del VIH. Las muestras de este estudio también pueden ser utilizadas en conjunto con los resultados de la investigación farmacogenética de otros estudios clínicos para cumplir este objetivo. |
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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 |
- Hombres y mujeres no embarazadas con infección crónica por el VIH 1 - Antecedentes de TAR con resistencia histórica o basal documentada, falta de tolerabilidad y/o contraindicaciones a los ARV en al menos tres familias - Fracaso del TAR actual con un ARN del VIH 1 plasmático ? 400 c/ml confirmado (primer valor del investigador, segundo de los laboratorios de selección) - Tener ? 2 familias con al menos 1 pero no más de 2 ARV plenamente activos restantes que se puedan combinar eficazmente para constituir un régimen viable nuevo, basado en el test de resistencias histórico documentado y/o actual y en la tolerabilidad y la seguridad - Capaces de recibir ? 1antirretroviral plenamente activo aprobado como parte del TBO desde el día 9 en adelante en la cohorte aleatorizada - Los sujetos sin ARV aprobados plenamente activos restantes se pueden reclutar en la cohorte no aleatorizada |
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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) |
- Infección crónica por el VHB no tratada (sin embargo, los pacientes con infección crónica por el VHB tratada son elegibles) - Infección por el VIH-2 - ALT o AST > 7 x límite superior de normalidad (LSN) - Fosfatasa alcalina > 5 x LSN - Bilirrubina ? 1,5 x LSN (salvo que el sujeto esté tomando actualmente atazanavir y tenga predominantemente hiperbilirrubinemia no conjugada) |
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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. |
La eficacia de BMS-663068, en relación con placebo, se evalúa usando el cambio medio en el log10 del ARN del VIH 1 desde el día 1 (momento basal) hasta el día 8, determinado por métodos de máxima verosimilitud. |
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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) |
En el día 8 tras el inicio de BMS-663068 enmascarado (o Placebo) + tratamiento de base optimizado (TBO). |
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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 |
- Proporción de sujetos con descensos del ARN del VIH 1 desde la basal superiores a 0,5 log10 c/ml y 1 log10 c/ml comparando la medición basal del ARN del VIH 1 de cada sujeto con su medición del día 8. Los sujetos sin datos a día 8 se clasifican como fracasos. - Durabilidad de la respuesta (ARN del VIH 1 < 40 c/ml) a semana 24 de TBO usando el algoritmo snapshot de la FDA. - Frecuencia de AAG, AA que conducen a suspensión y anomalías de laboratorio de grado 3-4 durante el TBO según los cuadernos de recogida de datos (CRD) y datos de laboratorio. -Progresión de la enfermedad durante el TBO según la aparición de los nuevos eventos definitorios de SIDA (clase C de los CDC) o la muerte a partir de los CRD. - Resistencias al fármaco evaluadas mediante tests de resistencias fenotípicos y genotípicos de aislados de sujetos identificados como cumplidores de los criterios de fracaso virológico. - Los cambios en los recuentos y porcentajes de linfocitos T CD4+, para BMS-663068 y placebo, se determinan usando los cambios medios desde el momento basal (día 1) hasta el día 8. - Los cambios respecto al momento basal en el ARN del VIH 1, los recuentos y el porcentaje de linfocitos T CD4+ para BMS-663068 cuando se administra con TBO, se evalúan usando resultados de laboratorio recogidos hasta la semana 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 |
Resistance testing |
Test de resistencia |
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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 | 5 |
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 |
Última visita de seguimiento del último sujeto |
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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 |