E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients of RALAM study (NCT02284035) |
Pacientes del estudio RALAM (NCT02284035) |
|
E.1.1.1 | Medical condition in easily understood language |
Patients of RALAM study |
Pacientes del estudio RALAM |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020445 |
E.1.2 | Term | Human immunodeficiency virus type I infection with constitutional disease |
E.1.2 | System Organ Class | 100000020168 |
|
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 |
Efficacy assessed with standard plasma HIV-1 RNA detection (limit of detection 50 copies/mL) at 48 weeks |
Evaluar la eficacia con la detección de ARN del VIH-1 en plasma estándar (definiendo el límite de detección en 50 copias/mL) a las 48 semanas |
|
E.2.2 | Secondary objectives of the trial |
- efficacy assessed with ultrasensitive HIV-1 RNA detection - change in peripheral mononuclear blood cells HIV-1 reservoir - changes in metabolic parameters including fasting plasma lipids and insulin resistance - change in body fat distribution - change in lumbar and femoral bone mineral density - change in plasma 25-OH vitamin D levels - change in estimated glomerular filtration rate, urine protein/creatinine ratio and urine beta-2-microglobulin - changes in immune activation markers including CD38 and HLA-DR - changes in biomarkers of inflammation and biomarkers of mononuclear activation - change in sleep quality - change in quality of life and overall satisfaction - overall tolerability |
- evaluar eficacia con la detección ultrasensible de ARN del VIH-1 - cambio en el reservorio de células mononucleares periféricas de la sangre VIH-1 - cambios en parámetros metabólicos incluyendo plasma lípidos en ayunas y resistencia a la insulina - cambios en la composición de grasa corporal - cambios en la densidad mineral ósea de los huesos femoral y lumbares - cambios en la concentración plasmática de 25-OH vitamina D - cambios en la tasa de filtración glomerular estimada, en el cociente proteína/creatinina de orina y en la concentración de beta-2-microglobulina - cambios en los marcadores de activación inmune - cambios en biomarcadores de la inflamación y biomarcadores de activación celular mononuclear - cambios en la la calidad del sueño - cambios en la calidad de vida y satisfacción - tolerabilidad general |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Patients in the switch arm who have completed the 24-week follow-up of RALAM (NCT02284035) study and remain virologically suppressed (viral load <50 copies/mL) on dual therapy with 3TC plus Raltegravir b. Patients who have signed informed consent to participate in the study. |
a. Los pacientes en el brazo de cambio que han completado el seguimiento de 24 semanas de RALAM (NCT02284035) estudio y permanecer virológicamente suprimido (carga viral <50 copias / mL) en la terapia dual con 3TC más Raltegravir b. Pacientes que han firmado el consentimiento informado para participar en el estudio. |
|
E.4 | Principal exclusion criteria |
a. Pregnancy, lactation, or planned pregnancy during the study period b. Any disease or history of disease which, in opinion of the investigator, might confound the results of the study or pose additional risk to patient treatment c. Hepatitis B co-infection |
a. Embarazo, lactancia o planificar embarazo durante el período de estudio b. Cualquier enfermedad o antecedente de enfermedad que, en opinión del investigador, pudiera confundir los resultados del estudio o plantear un riesgo adicional al tratamiento del paciente c. Co-infección por hepatitis B |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Therapeutic failure at week 48, includes virological failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death. |
Fracaso terapéutico en la semana 48, incluye el fracaso virológico, cambios en tratamiento por cualquier motivo, retiro de consentimiento, pérdida de seguimiento o muerte. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Proportion of patients with viral load below ultrasensitive HIV-1 RNA detection limit (limit of detection 1 copy/mL) at 48 weeks - Change from baseline in peripheral mononuclear blood cells HIV-1 reservoir to week 48 - Changes from baseline in metabolic parameters including fasting plasma lipids (cholesterol total, LDL, HDL and triglycerides) and insulin resistance (HOMA-IR) at 48 weeks - Change from baseline in lumbar and femoral bone mineral density to week 48 - Change from baseline in plasma 25-OH vitamin D levels to week 48 - Change from baseline in estimated glomerular filtration rate (CKD-EPI), urine protein/creatinine ratio and urine beta-2-microglobulin to week 48 - Changes from baseline in biomarkers of inflammation (IL-6, high sensitivity C-reactive protein) and biomarkers of mononuclear activation (SD-14, SD-163) at 48 weeks - Changes from baseline in sleep quality (Pittsburgh Sleep Quality Index) at 48 weeks - Change from baseline in quality of life (QoL) and overall satisfaction (VAS) at 48 weeks - Incidence of adverse events |
- Proporción de pacientes con carga viral por debajo del límite de detección del ARN del VIH-1 ultrasensible (límite de detección 1 copia / mL) a las 48 semanas - Cambio de la línea de base en el depósito de VIH-1 de las células sanguíneas mononucleares periféricas a la semana 48 - Cambios desde la línea de base en los parámetros metabólicos incluyendo los lípidos plasmáticos en ayunas (colesterol total, LDL, HDL y triglicéridos) y resistencia a la insulina (HOMA-IR) a las 48 semanas - Cambio desde la línea base de la densidad mineral ósea lumbar y femoral a las 48 semanas - Cambio desde la línea de base en los niveles plasmáticos de 25-OH de vitamina D a las 48 semanas - Cambio desde la línea de base en la tasa estimada de filtración glomerular (CKD-EPI), relación orina proteína / creatinina y beta-2-microglobulina en la orina a las 48 semanas - Cambios desde la línea base en biomarcadores de inflamación (IL-6, proteína C reactiva de alta sensibilidad) y biomarcadores de activación mononuclear (SD-14, SD-163) a las 48 semanas - Cambios desde la línea de base en la calidad del sueño (índice de calidad del sueño de Pittsburgh) a las 48 semanas - Cambio de la calidad de vida (QoL) y la satisfacción general (VAS) a las 48 semanas - Incidencia de eventos adversos |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.5 | Efficacy | No |
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 | No |
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 | 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 | No |
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.8.5 | 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 | Yes |
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
|
DSMB will review the data if 4 episodes of treatment failure are detected and subsequently every 4 new episodes of treatment failure. Study will be interrupted as soon as 5 episodes (10%) of confirmed virological failure are detected. |
DSMB revisará los datos si se detectan 4 episodios de fracaso del tratamiento y posteriormente cada 4 nuevos episodios de fracaso del tratamiento. Estudio se interrumpirá en cuanto se detectan 5 episodios (10%) de fracaso virológico confirmado. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |