E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recent HIV-1 infection |
Infección reciente por VIH |
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E.1.1.1 | Medical condition in easily understood language |
Recent HIV-1 infection |
Infección reciente por VIH |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058427 |
E.1.2 | Term | Primary HIV infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The overall objective of the project is to evaluate the safety and tolerability of a new therapeutic strategy, based on the administration of dasatinib, an ITK. The safety and tolerability of dasatinib will be evaluated in patients with recent (3-12 months) asymptomatic HIV-1 infection. |
El objetivo global del proyecto es evaluar la seguridad y tolerancia de una nueva estrategia terapéutica, basada en la administración de dasatinib, un ITK. Se evaluará la seguridad y tolerancia del dasatinib en pacientes con infección reciente (entre 3 y 12 meses) asintomática por el VIH-1. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the in vivo antiretroviral capacity of dasatinib by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy. 2. To assess changes in the viral reservoirs of patients with recent HIV-1 infection induced by dasatinib administration. 3. To assess changes in markers of inflammation and immune activation induced by dasatinib administration. 4. To assess the changes in SAMHD1 phosphorylation levels and cytotoxic activity against HIV-1 induced by dasatinib. 5. To assess the tolerability and pharmacokinetic interactions of co-administration of non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib. 6. To assess the impact of dasatinib on markers of senescence. |
1. Evaluar la capacidad antirretroviral propia in vivo del dasatinib mediante la cuantificación de la carga viral plasmática de VIH-1 durante la administración de dasatinib en monoterapia durante 4 semanas. 2. Evaluar los cambios en los reservorios virales de pacientes con infección reciente por el VIH-1 inducidos por la administración de dasatinib. 3. Evaluar los cambios en los marcadores de inflamación y activación inmunológica inducidos por la administración de dasatinib. 4. Evaluar los cambios en los niveles de fosforilación de SAMHD1 y en la actividad citotóxica frente al VIH-1 inducidas por el dasatinib. 5. Evaluar la tolerancia y las interacciones farmacocinéticas de la coadministración del tratamiento antirretroviral basado en inhibidores de la integrasa no potenciados con dasatinib. 6. Evaluar el impacto del dasatinib en los marcadores de senescencia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients included in the study must meet the following criteria: -18 to 65 years. -Documented asymptomatic HIV-1 infection of 3-12 months duration (all patients must have a positive Western blot, including the p31 band whose appearance indicates infection of more than 90 days duration). -Not having received ART -CD4 T-lymphocyte count> 350 / μl -Patient giving written informed consent |
Los pacientes incluidos en el estudio deberán cumplir los siguientes criterios: -18 a 65 años. -Infección asintomática por VIH-1 documentada de entre 3 y 12 meses de duración (todos los pacientes deben tener un Western blot positivo, incluyendo la banda p31 cuya aparición indica una infección de más de 90 días de duración). -No haber recibido TAR -Recuento de linfocitos T CD4> 350 / μl -Paciente que otorgue el consentimiento informado por escrito |
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E.4 | Principal exclusion criteria |
Potential participants who meet any of the following criteria will be excluded from the study: -HBV positive serology (any marker except HBsAb after vaccination) or HCV positive RNA. -ALT> 2 UNL, glomerular filtration rate <70 mL / 1.73 m2, leukocytes <4000 / mm3, total lymphocyte count <1000 / mm3, platelets <100,000 / mm3 or Hg <12g / dL. -Pregnancy or active breastfeeding -Ongoing or previous pleural effusion -Chronic obstructive pulmonary disease, bronchial asthma or recent chest trauma. -History of gastrointestinal or other bleeding. -Any concomitant treatment with potentially dangerous drug interaction with dasatinib. -Any clinical condition, at the opinion of the investigator, contraindicating participation (for example, -Active neoplastic disease, active concomitant infection, etc.) -Resistance to integrase inhibitors (raltegravir, dolutegravir, bictegravir) or analogues |
Los potenciales participantes que cumplan algunos de los siguientes criterios serán excluidos del estudio: -Serología positiva para el VHB (cualquier marcador, excepto HBsAb después de la vacunación) o RNA positivo para el VHC. -ALT> 2 UNL, filtrado glomerular <70 mL / 1,73 m2, leucocitos <4000 / mm3, Recuento de linfocitos totales <1000 /mm3, Plaquetas <100.000 / mm3 o Hg <12g / dL -Embarazo o lactancia materna activa -Derrame pleural en curso o previo -Enfermedad pulmonar obstructiva crónica, asma bronquial o traumatismo torácico reciente. -Historia de sangrado digestivo o de otro tipo. -Cualquier tratamiento concomitante con interacción farmacológica potencialmente peligrosa con dasatinib -Cualquier condición clínica, a discreción del investigador, contraindicando la participación (por ejemplo, -enfermedad neoplásica activa, infección concomitante activa, etc.) -Resistencia a los inhibidores de la integrasa (raltegravir, dolutegravir, bictegravir) o análogos |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is to assess the safety and tolerability of dasatinib with and without antiretroviral therapy using the incidence of AA. |
La variable principal del estudio es evaluar la seguridad y tolerancia del dasatinib con y sin tratamiento antirretroviral mediante la incidencia de AA. |
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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) |
Immunological endpoints: -immune recovery (CD4 subpopulation levels). -inflammatory markers (ultra-sensitive CRP, IL6, TNF alpha) -immune activation (CD4/CD8, CD25, CD69, CD38, HLA-DR+) -bacterial translocation (rsCD163) -levels of NK-mediated cytotoxic activity (NK phenotyping and in vitro replication inhibition tests). Virological endpoints: -decline in HIV viral load prior to ART initiation (4 weeks of dasatinib monotherapy) -impact on the viral reservoir (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites) -SAMHD1 phosphorylation levels senescence endpoints: -Expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87. |
Criterios de valoración inmunológicos: -recuperación inmune (niveles de subpoblaciones CD4) -marcadores inflamatorios (PCR ultrasensible, IL6, TNF alfa) -activación inmunológica (CD4/CD8, CD25, CD69, CD38, HLA-DR+) -translocación bacteriana (rsCD163) -niveles de actividad citotóxica mediada por NK (fenotipado de NK y tests de inhibición de replicación “in vitro” Criterios de valoración virológicos: -disminución de la carga viral del VIH antes del inicio del TAR (4 semanas de monoterapia con dasatinib -impacto sobre el reservorio viral (DNA integrado, virus genéticamente intactos replicación viral residual e inducida y determinación de sitios de integración) -niveles de fosforilación de SAMHD1 Criterios de valoración de senescencia: -Expresión en PBLs de beta-galactosidasa, Bcl-2, Histona H2A, p16 y CD87. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These parameters will be measured at baseline (S0, start of dasatinib), at the start of ART (S4), at the end of dasatinib (S16) and at S48 of ART (S52). |
Estos parámetros se medirán basalmente (S0, inicio de dasatinib), al inicio del TAR (S4), al finalizar el dasatinib (S16) y a la S48 del tratamiento antirretroviral (S52). |
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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 | 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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
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
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LVLS |
LVLS (última visita último paciente) |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | |