E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients infected with HIV and without previous antiretroviral treatment. |
Pacientes adultos infectados por el VIH y sin tratamiento antirretroviral previo. |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients infected with HIV and without previous antiretroviral treatment. |
Pacientes adultos infectados por el VIH y sin tratamiento antirretroviral previo. |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
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 |
To evaluate the safety and efficacy of Vedolizumab in combination with ART to achieve remission of Plasma viral load at undetectable levels in persons infected with HIV-1 without previous antiretroviral treatment after ART.
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Evaluar la seguridad y eficacia de Vedolizumab combinado con TAR para conseguir la remisión de la carga viral Plasma a niveles indetectables en personas infectadas por el VIH-1 sin tratamiento antirretroviral previo tras la iTAR |
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E.2.2 | Secondary objectives of the trial |
Thorough virological and immunological characterization in peripheral blood and in lymphoid tissue associated with intestine (GALT). |
Caracterización virológica e inmunológicam exhaustiva en sangre periférica y en tejido linfoide asociado a intestino (GALT) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with HIV infection and age ≥ 18 years and <65 years. - Detectable viremia (>1x104 copies RNA/ ml ) - Levels of CD4 + > 350 cells / μL. - Accept analytical interruption of the treatment. - Written informed consent. |
- Pacientes con infección por el VIH-1 y edad ≥ 18 y <65 años. - Viremia detectable (>1x104 copias ARN VIH-1/ml). - Niveles de CD4+ >350 células/μL. - Aceptar interrupción analítica del tratamiento. - Consentimiento informado por escrito. |
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E.4 | Principal exclusion criteria |
- Presence of major resistance mutations to any of the study drugs. - Active opportunistic infections. - Pregnancy. - Active co-infection with hepatitis B or C virus or latent infection with untreated TB. - Cirrhosis, portal hypertension and / or hypersplenism of any etiology. - Past or current neoplasms subsidiary to treatment with steroids, immunomodulators or chemotherapy - Laboratory abnormalities grade 3 or 4. - Concomitant use of drugs with greater pharmacological interactions with the study drugs, according to the respective technical specifications of the products. - Estimated creatinine clearance < 50ml / min. - Have received any type of vaccination (eg, hepatitis B virus, influenza ...) two weeks before the start of the study. - Cardiovascular disease (eg, angina, heart failure, recent acute coronary syndrome) - Neurological or neuropsychiatric disease whose symptoms may interfere with the assessment of safety and tolerability. - Active abuse of alcohol and / or drugs or any pattern of behavior that, in the opinion of the researcher, could interfere with adherence to study drugs |
- Presencia de mutaciones de resistencia mayores a cualquiera de los fármacos del estudio. - Infecciones oportunistas activas. - Embarazo. - Co-infección activa por virus B o C de la hepatitis o infección latente por TB no tratada. - Cirrosis, hipertensión portal y/o hiperesplenismo de cualquier etiología. - Neoplasias pasadas o actuales subsidiarias de tratamiento con esteroides, inmunomoduladores o quimioterapia - Anomalías de laboratorio grado 3 o 4. - Utilización concomitante de fármacos con interacciones farmacológicas mayores con los fármacos de estudio, según las respectivas fichas técnicas de los productos. - Aclaramiento estimado de creatinina <50ml/min. - Haber recibido cualquier tipo de vacunación (por ej. virus de la hepatitis B, gripe…) dos semanas antes del comienzo del estudio. - Enfermedad cardiovascular (por ej. angina, insuficiencia cardiaca, síndrome coronario agudo reciente) - Enfermedad neurológica o neuropsiquiátrica cuyos síntomas pudieran interferir con la evaluación de la seguridad y tolerabilidad. - Abuso activo de alcohol y/o drogas o cualquier patrón de comportamiento que, en la opinión del investigador, pudiera interferir en la adherencia a los fármacos del estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Adverse events and their degree 2. Efficacy of Vedolizumab combined with antiretroviral treatment evaluated as the reappearance or not of HIV-1 viremia, evolution of the CD4 + lymphocyte count and the need to restart ART after finishing the infusions of Vedolizumab and suspend the concomitant ART. |
1. Eventos adversos y su grado 2. Eficacia de Vedolizumab combinado con tratamiento antirretroviral evaluado como la reaparición o no de viremia VIH-1, evolución del recuento de linfocitos CD4+ y la necesidad de reiniciar TAR tras finalizar las infusiones de Vedolizumab y suspender el TAR concomitante. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During infusions and patient follow-up. |
Durante las infusiones y el siguimiento del paciente. |
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E.5.2 | Secondary end point(s) |
- Subpopulations of T cells, dendritic cells, monocytes, NK cells and innate lymphoid cells in PBMCs and in GALT (two ileal and cecum locations). - Array of cytokines, chemokines and inflammatory markers including retinoic acid. - Integrity of the tissue by immunohistochemical and immunofluorescence techniques. - Levels of RNA-HIV-1 in blood plasma RNA and DNA of HIV-1 associated with PBMCs and GALT. - Immunoprecipitation of HIV-1 from host molecules (α4β7, CD29, CD54, CD11a, HLA-ABC, HLA-DR, CD27, CD43, CD45, CD46 and CD102). - Detection of Vedolizumab levels. - Detection of anti-Vedolizumab antibodies. |
- Subpoblaciones de células T, células dendríticas, monocitos, células NK y células linfoides innatas en PBMCs y en GALT (dos localizaciones íleon y ciego). - Array de citoquinas, quimiocinas y marcadores inflamatorios incluyendo el ácido retinoico. - Integridad del tejido por técnicas inmunohistoquímicas y de inmunofluorescencia. - Niveles de ARN-VIH-1 en plasma sanguíneo ARN y ADN de VIH-1 asociados a PBMCs y a GALT. - Inmunoprecipitación de VIH-1 a partir de moléculas del hospedador (α4β7, CD29, CD54, CD11a, HLA-ABC, HLA-DR, CD27, CD43, CD45, CD46 y CD102). - Detección de niveles de Vedolizumab. - Detección de anticuerpos anti-Vedolizumab. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Peripheral blood: At the second visit, one week before each infusion until week 24 and every 4 weeks until week 48. GALT: The second visit and between weeks 32 and 36. |
Sangre periférica:En la segunda visita, una semana antes de cada infusión hasta semana 24 y cada 4 semanas hasta la semana 48. GALT: La segunda visita y entre las semanas 32 y 36. |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.3 |
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
|
Final visit of the last patient included. |
El día de la visita final del último paciente incluido. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |