E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infected individuals |
Personas infectadas con VIH-1 |
|
E.1.1.1 | Medical condition in easily understood language |
HIV-1 infected individuals |
Personas infectadas con VIH-1 |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 Bictegravir concentrations in CSF and to estimate penetration into the CNS. -To evaluate antiviral activity of a combination of TAF/FTC/BIC in CSF. |
- Evaluar las concentraciones de Bictegravir en LCR y estimar la penetración en el SNC. - Evaluar la actividad antiviral de una combinación de TAF / FTC / BIC en CSF. |
|
E.2.2 | Secondary objectives of the trial |
- To assess Bictegravir concentrations in CSF and to estimate penetration into the CNS. -To evaluate antiviral activity of a combination of TAF/FTC/BIC in CSF. |
- Evaluar las concentraciones de Bictegravir en LCR y estimar la penetración en el SNC. - Evaluar la actividad antiviral de una combinación de TAF / FTC / BIC en CSF. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Asymptomatic, HIV-1 infected individuals ≥ 18 years of age - Be on a stable ART consisting of TDF/FTC or ABC/3TC plus 1NNRTI, 1 boosted PI or 1 integrase inhibitor, continously or ≥3 consecutive months preceding the screening visit. Patients already receiving TAF/FTC/BIC for at least three consecutive months will be eligible. - Plasma HIV-1 RNA at screening <40 copies/mL for at least 6 months at the Screening visit. - Signed and dated written informed consent prior to inclusion. - Subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study. |
- Individuos asintomáticos, infectados por VIH-1 ≥ 18 años de edad - Estar en un TAR estable que consiste en TDF / FTC o ABC / 3TC más 1NNRTI, 1 IP potenciado o 1 inhibidor de integrasa, continuamente o ≥ 3 meses consecutivos antes de la visita de selección. Los pacientes que ya reciban TAF / FTC / BIC durante al menos tres meses consecutivos serán elegibles. - ARN de VIH-1 plasmático en el cribado <40 copias / ml durante al menos 6 meses en la visita de cribado. - Firmado y fechado el consentimiento informado por escrito antes de la inclusión. - Los sujetos deben estar de acuerdo en utilizar un método anticonceptivo altamente efectivo durante las relaciones sexuales heterosexuales desde la visita de selección durante todo el estudio. |
|
E.4 | Principal exclusion criteria |
- Severe hepatic impairment (Child-Pugh Class C) - Ongoing malignancy - Active opportunistic infection - Primary resistance to any of the ARV included in the study or history of virologic failure with risk of resistance selection to any of the study drugs. - Any verified Grade 4 laboratory abnormality - ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN - Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min - Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding. - Current treatment with antiaggregant or anticoagulant therapy. - History of any neurologic disease/condition/treatment may alter the blood brain barrier permeability. |
- Insuficiencia hepática grave (clase C de Child-Pugh) - Malignidad en curso - infección oportunista activa - Resistencia primaria a cualquiera de los ARV incluidos en el estudio o historial de falla virológica con riesgo de selección de resistencia a cualquiera de los medicamentos del estudio. - Cualquier anomalía verificada de laboratorio de Grado 4 - ALT o AST ≥ 3xULN y / o bilirrubina ≥ 1.5xULN - Función renal adecuada: tasa estimada de filtración glomerular ≥ 50 ml / min - Mujeres embarazadas (confirmadas por una prueba de embarazo en suero positiva) o amamantando. - Tratamiento actual con terapia antiagregante o anticoagulante. - La historia de cualquier enfermedad / condición / tratamiento neurológico puede alterar la permeabilidad de la barrera hematoencefálica. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- To determine total and unbound Bictegravir concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with TAF/FTC/Bictegravir. -Total Bictegravir concentrations in blood plasma. - Bictegravir CSF/plasma ratio. -HIV-1 RNA in cerebrospinal fluid. -HIV-1 RNA in blood plasma. |
- Determinar las concentraciones totales y sin unir de Bictegravir en el líquido cefalorraquídeo en individuos infectados con VIH-1 que reciben ART con TAF / FTC / Bictegravir. -Total de las concentraciones de Bictegravir en el plasma sanguíneo. - Bictegravir CSF / relación de plasma. -HIV-1 ARN en fluido cerebroespinal. -HIV-1 ARN en plasma sanguíneo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
|
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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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
|
LVLS |
la última visita del último sujeto |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |