E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human immunodeficiency virus (HIV) infection. |
Infección por el virus de la inmunodeficiencia humana (VIH). |
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E.1.1.1 | Medical condition in easily understood language |
HIV infection. |
Infección por el VIH. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 | 10008922 |
E.1.2 | Term | Chronic infection with HIV |
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 |
Assess whether the determination of viral tropism from proviral DNA in PBMCs is a suitable technique to guide treatment with CCR5 antagonists in patients with undetectable viral load who need antiretroviral treatment change for reasons of tolerability or adverse effects. |
Evaluar si la determinación de tropismo viral a partir del ADN proviral en PBMCs es una técnica adecuada para guiar el tratamiento con antagonistas de CCR5 en pacientes con carga viral indetectable que necesitan un cambio de tratamiento antirretroviral por razones de tolerabilidad o efectos adversos. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the virological efficacy of a treatment.
2. Evaluate other aspects related to the maintenance of virologic response.
3. Assess changes in the tropism of HIV-1 during the study.
4. Assess the tolerability and safety of a treatment. |
1. Evaluar la eficacia virológica del tratamiento.
2. Evaluar otros aspectos relacionados con el mantenimiento de la respuesta virológica del tratamiento.
3. Evaluar los cambios en el tropismo del VIH-1 a lo largo del estudio.
4. Evaluar la tolerabilidad y seguridad del tratamiento. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult (18 years or more), HIV-1 infected patients. Antiretroviral treatment for at leasdt 6 months containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) plus 1 Non-nucleoside reverse-transcriptase inhibitor (NNRTI) or 1 protease inhibitor (PI) or 1 integrase inhibitor (ININ) Viral load under 50 copies/mL in the last 6 months Patients with CCR5 tropism based in V3 genotyping in proviral DNA using the G2P with a false positive rate of 10% interpretation method. A change of treatment is needed due to toxicity / tolerability problems with the 3rd drug (PI, NNRTI or ININ), according to investigator criteria. |
Pacientes adultos (18 años o mayoreS), infectados por el VIH-1. Tratamiento antirretroviral durante al menos 6 meses que contenga 2 inhibidores de la transcriptasa inversa análogos de nucleósidos (ITIAN) más: 1 inhibidor de la transcriptasa inversa no análogo de nucleósido (ITINAN) ó 1 inhibidor de la proteasa (IP) ó 1 inhibidor de la integrasa (ININ). Carga viral <50 copias/mL en los últimos 6 meses. Pacientes con tropismo CCR5 basado en genotipado poblacional de V3 en ADN proviral usando el método de interpretación G2P con una tasa de falsos positivos (TFP) del 10%. Se requiere un cambio de tratamiento debido a problemas de toxicidad / tolerabilidad con el tercer fármaco, de acuerdo con el criterio del investigador. |
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E.4 | Principal exclusion criteria |
Pregnancy or breast-feeding. Patient previously treated with maraviroc. Patients with documented resistance to maraviroc or any other drug considered for the new ARV regimen. Viral failure in the moment of inclusion. Bad adherence history or anticipated (investigator criteria). |
Mujeres embarazadas o en período de lactancia. Pacientes tratados previamente con maraviroc. Pacientes con resistencia documentada a maraviroc u otro fármaco considerado para el nuevo esquema antirretroviral. Fracaso virológico en el momento de la inclusión. Pacientes con historial de mala adherencia o mala adherencia anticipada a criterio del investigador. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sustained virologic suppression at 48 weeks of treatment (viral load). |
Supresión virológica mantenida a las 48 semanas de tratamiento (carga viral). |
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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) |
Evaluate other aspects related to the maintenance of virologic response. - Percentage of patients without confirmed virologic failure - Time to confirmed virological failure - Time to loss of virologic response (TLOVR) <200 copies / mL. - Time to loss of virologic response (TLOVR) <50 copies / mL. - Proportion of patients with undetectable viral load (VL <50 copies / mL) after 12, 24, 36 and 48 weeks of treatment with antiretroviral scheme including maraviroc. - Time to discontinuation of treatment, general and due to factors other than loss of virologic response. - Median change in CD4 count at weeks 12, 24, 36 and 48 compared with baseline.
Assess changes in HIV-tropism: - Association between the level of detection of CCRX4 by 454 ultra deep sequencing in the screening and virologic response to antiretroviral scheme including maraviroc. - Change in proviral tropism by poblational genotyping and by 454 ultra deep sequencing genotyping in 35 randomly-selected patients. - Assessment of viral diversity and the level of CXCR4 using 454 ultra deep sequencing at week 12 and at the time of virologic failure (only in cases of virologic failure.)
To assess the tolerability and safety of antiretroviral regimen including a CCR5 antagonist. - Median changes in fasting lipid parameters (total cholesterol, LDL and HDL, and triglycerides) compared with baseline. - Changes in liver function tests (AST, ALT, alkaline phosphatase and total bilirubin). - Cumulative number of adverse events at weeks 4, 12, 24, 36 and 48. - Cumulative number of grade 3-4 adverse events at weeks 4, 12, 24, 36 and 48. - Proportion of patients who prematurely terminated and reason for termination. |
Evaluar otros aspectos relacionados con el mantenimiento de la respuesta virológica. - Porcentaje de pacientes sin fracaso virológico confirmado - Tiempo hasta fracaso virológico confirmado - Tiempo hasta la pérdida de la respuesta virológica (TLOVR) <200 copias/mL. - Tiempo hasta la pérdida de la respuesta virológica (TLOVR) <50 copias/mL. - Proporción de pacientes con carga viral indetectable (CV <50 copias/mL) después de 12, 24, 36 y 48 semanas de tratamiento con un esquema antirretroviral incluyendo maraviroc. - Tiempo hasta la interrupción del tratamiento, general y debido a factores distintos a la pérdida de respuesta virológica. - Mediana de cambio del recuento de CD4 en las semanas 12, 24, 36 y 48 comparado con el basal.
Evaluar los cambios en el tropismo del VIH
- Asociación entre el nivel de CCRX4 detectados por pirosecuenciación masiva por 454 en el screening y la respuesta virológica al esquema antirretroviral incluyendo maraviroc. - Cambio en el tropismo proviral por genotipado poblacional y por pirosecuenciación masiva por 454 en 35 pacientes representativos seleccionados al azar. - Evaluación de la diversidad viral y del nivel de CXCR4 usando pirosecuenciación masiva por 454 a la semana 12 y en el momento del fracaso virológico (sólo en los casos de fracaso virológico).
Evaluar la tolerabilidad y seguridad de un esquema antirretroviral incluyendo un antagonista de CCR5.
Endpoints de seguridad incluyen: - Mediana de cambios en parámetros lipídicos en ayunas (colesterol total, LDL y HDL y triglicéridos) comparado con el basal. - Cambios en los parámetros de función hepática (AST, ALT, fosfatasa alcalina y bilirrubina total). - Número acumulativo de acontecimientos adversos en la semanas 4, 12, 24, 36 y 48. - Número acumulativo de acontecimientos adversos de grado 3-4 en la semanas 4, 12, 24, 36 y 48. - Proporción de pacientes que finalizan prematuramente y motivo de finalización. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening, baseline, week 4, week 12, week 24, week 36 and week 48. |
Screening, basal, semana 4, semana 12, semana 24, semana 36 y semana 48. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 28 |
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
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Last visit of last patient included in the trial. |
La última visita del último sujeto incluido en el ensayo. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |