E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infection |
Infección por VIH |
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E.1.1.1 | Medical condition in easily understood language |
HIV-1 infection |
Infección por VIH |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020192 |
E.1.2 | Term | HIV-1 |
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 primary objective is to demonstrate non-inferiority in terms of the percentage of subjects who have plasma HIV-1 RNA levels <50 copies/mL after 48 weeks of follow-up after switching to DRV/rtv monotherapy versus triple therapy containing DRV/rtv (FDA Snapshot method). |
El objetivo principal es demostrar la no inferioridad en términos del porcentaje de sujetos con unos niveles de ácido ribonucleico (ARN) del virus de la inmunodeficiencia humana de tipo 1 (VIH-1) en plasma <50 copias/mL a las 48 semanas de seguimiento tras el cambio a la monoterapia con DRV/ritonavir (rtv), en comparación con una triterapia que contiene DRV/rtv (método Snapshot de la FDA). |
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E.2.2 | Secondary objectives of the trial |
1. the correlation of plasma HIV-1 RNA, cerebrospinal fluid (CSF) HIV-1 RNA, and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at week 48 2. change in neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks 3. the rate of plasma HIV-1 RNA suppression after 48 and 96 weeks of follow-up to DRV/rtv monotherapy versus triple therapy containing DRV/rtv, using the time to loss of virologic response (TLOVR) method. 4. the correlation of plasma HIV-1 RNA and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96 5. the loss of treatment options as defined by treatment-emergent phenotypic drug resistance 6. the viral genotype of subjects 7. To evaluate and compare safety and tolerability |
?Evaluar la correlación entre ARN del VIH-1 en plasma, ARN del VIH-1 en líquido cefalorraquídeo (CSF) y función neurocognitiva ?Evaluar y comparar los cambios en la función neurocognitiva con la monoterapia con DRV/rtv frente a una triterapia que contiene DRV/rtv a lo largo de 48 y 96 semanas. ?Evaluar y comparar la tasa de supresión del ARN del VIH-1 en plasma autilizando el método del tiempo hasta la pérdida de la respuesta virológica (TLOVR). ?Evaluar la correlación entre el ARN del VIH-1 en plasma y la función neurocognitiva con la monoterapia con DRV/rtv frente a una triterapia que contiene DRV/rtv en las Semanas 48 y 96. ?Comparar la pérdida de opciones terapéuticas en su definición mediante la resistencia fenotípica a la medicación emergente en el tratamiento. ?Evaluar la evolución del genotipo viral de los sujetos ?Evaluar y comparar la seguridad y la tolerabilidad |
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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 |
a lumbar puncture (extraction of cerebrospinal fluid [CSF] from the spinal canal) for laboratory testing (antiviral effectiveness, pharmacokinetic analysis, biochemistry and immune markers) and an additional blood sample for pharmacokinetic analysis (to measure the drug level in blood) will be taken. The study hypothesis is that, after 48 weeks of randomised treatment, DRV/rtv monotherapy is as effective as the triple therapy containing DRV/rtv plus plus 2 nucleoside analogues |
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E.3 | Principal inclusion criteria |
HIV-1 infection; receiving HAART for at least 48 weeks; Have plasma HIV-1 RNA <50 copies/mL for at least 48 weeks prior to screening; Be taking the same antiretroviral (ARV) combination for at least 8 weeks before screening; Have the preference, together with the physician, to change the current HAART regimen for reasons of simplification and/or toxicity |
1Presentar infección documentada por el VIH-1; Estar recibiendo un TARGA desde como mínimo 48 semanas antes; Poseer un ARN del VIH-1 en plasma <50 copias/mL desde como mínimo 48 semanas antes de la selección; Estar recibiendo la misma combinación de antirretrovirales desde como mínimo 8 semanas antes de la selección; Preferencia, junto con su médico, a cambiar su régimen de TARGA actual por razones de simplificación y/o toxicidad |
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E.4 | Principal exclusion criteria |
Has a history of virologic failure defined as 2 consecutive plasma HIV-1 RNA >500 copies/mL while on previous or current antiretroviral therapy; Has a history of any primary PI mutations; Has clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency); Is diagnosed with acute viral hepatitis at screening or before Baseline 1; Is co-infected with hepatitis B |
Tiene antecedentes de fracaso virológico, definido como 2 valores consecutivos de ARN del VIH-1 en plasma >500 copias/mL durante su tratamiento antirretroviral previo o actual. Tiene historia de cualquier mutación primaria frente a PI; Presenta evidencia clínica o de laboratorio de afectación significativa de la función hepática o de descompensación hepática, independientemente de sus niveles de enzimas hepáticas (insuficiencia hepática); Está co-infectado con hepatitis B |
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E.5 End points |
E.5.1 | Primary end point(s) |
the percentage of patients who have plasma human immunodeficiency virus type-1 (HIV-1) ribonucleic acid (RNA) levels <50 copies/mL after 48 weeks of follow-up after switching to DRV/ritonavir (rtv) monotherapy versus triple therapy containing DRV/rtv |
Porrcentaje de sujetos con una carga viral plasmática confirmada <50 copias/mL en la Semana 48 de segumiento |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
the correlation of plasma HIV-1 RNA, cerebrospinal fluid (CSF) HIV-1 RNA, and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at week 48
change in neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks
the rate of plasma HIV-1 RNA suppression after 48 and 96 weeks of follow-up to DRV/rtv monotherapy versus triple therapy containing DRV/rtv, using the time to loss of virologic response (TLOVR) method.
the correlation of plasma HIV-1 RNA and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96
the loss of treatment options of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96, as defined by treatment-emergent phenotypic drug resistance
the viral genotype of subjects treated with DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks
To evaluate and compare safety and tolerability of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
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 |
Tolerability |
Tolerabilidad |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
monotherapy vs triple combination therapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |