E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infection |
Infección por VIH-1 |
|
E.1.1.1 | Medical condition in easily understood language |
HIV infection |
Infección por VIH |
|
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 | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 assess the extend of persistent viral reservoir and the level of immune activation in patients receiving suppressive treatment with protease inhibitors. |
Evaluar la extensión del reservorio viral persistente y el nivel de activación inmune en los pacientes que recibieron tratamiento de supresión con inhibidores de la proteasa. |
|
E.2.2 | Secondary objectives of the trial |
? To asses the slope of decay of integrated and unintegrated viral DNA. ? An ultrasensitive RT-PCR assay with a lower limit of quantification of 3 copies/ml will be used to assess the possible decay of residual HIV-1 replication under RAL intensification. ? Effect of RAL intensification on the frequency of blips during the study. ? Changes in soluble CD14 |
? Evaluar la pendiente de la caída de ADN viral integrado y no integrado. ? Se utilizará PCR ultrasensible con un límite inferior de cuantificación de 3 copias / ml para evaluar la posible caida de replicación residual de VIH-1 bajo intensificación con RAL. ? Efecto de la intensificación con RAL en la frecuencia de los blips durante el estudio. ? Cambios de CD14 soluble |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. HIV-1 infected adults (?18 years old). 2. Absence of prior virological failure with PIs. 3. No mono or dual protease inhibitor therapy previous to HAART initiation. 4. Patients had to be on monotherapy with ritonavir-boosted lopinavir (LPV/r 200/50 mg BID) or darunavir (DRV/r 800/100 mg QD) for ? 12 months. Switching from standard HAART to protease inhibitor monotherapy had to happen with undetectable plasma viremia. 5. Complete virological suppression (<50 copies/mL) for ?12 months, including at least 3 times during the last year. 6. CD4 cell count ?500 cells/µL. 7. Availability (if possible, not mandatory) of a genotype prior to the start of HAART, with absence of any drug-related mutations and specifically of any polymorphism or mutation associated to Raltegravir resistance. 8. Voluntary written informed consent. |
1. Adultos infectados por VIH-1(? 18 años). 2. Ausencia de fracaso virológico previo a inhibidores de la proteasa. 3. No terapia mono o doble con un inhibidor de la proteasa anterior al inicio del TARGA. 4. Los pacientes tenían que estar en monoterapia con lopinavir potenciado con ritonavir (LPV / r 200/50 mg BID) o darunavir (DRV / r 800/100 mg QD) por ? 12 meses. El cambio de TARGA estándar a monoterapia con inhibidores de la proteasa tenía que ser con viremia indetectable en plasma. 5. Supresión virológica completa (<50 copias / mL) por ? 12 meses, incluyendo por lo menos 3 veces durante el año pasado. 6. Recuento de células CD4 ? 500 células / mm. 7. Disponibilidad (si es posible, no obligatorio) de un genotipo antes del inicio del TARGA, con ausencia de mutaciones relacionadas con el tratamiento y específicamente de cualquier polimorfismo o mutación asociada a resistencia a raltegravir. 8. Firma voluntaria del consentimiento informado. |
|
E.4 | Principal exclusion criteria |
1. Lactating, Pregnancy, or fertile women willing to be pregnant. 2. Active substance abuse or major psychiatric disease. 3. Presence of any polymorphism or mutation associated to RAL resistance at baseline (prior to first HAART). |
1. Período de lactancia, embarazo o mujeres en edad fértil dispuestas a estar embarazada. 2. Abuso activo de sustancias o enfermedad psiquiátrica mayor. 3. Presencia de cualquier polimorfismo o mutación asociada a resistencia a RAL al inicio (antes de la primera TARGA). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
? Change over a 24-week period in the detection of HIV-1 episomal DNA (2-LTR circles). ? Change over a 24-week period in lymphocyte activation markers in PBMCs. |
? Cambio en un período de 24 semanas en la detección del VIH-1 ADN episomal (2-LTR círculos). ? Cambio en un período de 24 semanas en los marcadores de activación de los linfocitos en PBMCs. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to 24 weeks |
Desde el basal hasta semana 24 |
|
E.5.2 | Secondary end point(s) |
? The slope of decay of integrated and unintegrated viral DNA. ? An ultrasensitive RT-PCR assay with a lower limit of quantification of 3 copies/ml will be used to assess the possible decay of residual HIV-1 replication under RAL intensification. ? Effect of RAL intensification on the frequency of blips during the study. ? Changes in soluble CD14 |
? Evaluar la pendiente de la caída de ADN viral integrado y no integrado. ? Se utilizará PCR ultrasensible con un límite inferior de cuantificación de 3 copias / ml para evaluar la posible caida de replicación residual de VIH-1 bajo intensificación con RAL. ? Efecto de la intensificación con RAL en la frecuencia de los blips durante el estudio. ? Cambios de CD14 soluble |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
From baseline to 24 weeks |
Desde el basal hasta semana 24 |
|
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 | 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) | 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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Auto-controlado, prueba de concepto |
Self-controlled, proof of concept |
|
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 |
Terapia basal sin intensificar con raltegravir |
Basal therapy without intensification with raltegravir |
|
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |