E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV+ infected subjects with undetectable replication competent HIV reservoir after allogeneic stem cell transplantation in presence of cART. |
Sujetos VIH+ con un reservorio viral competente indetectable después del trasplante alogénico de células madre en presencia de TAR. |
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E.1.1.1 | Medical condition in easily understood language |
HIV stable subjects with undetectable virus in cells who received a stem cell transplant |
Sujetos con infección crónica controlada de VIH y a quienes no se les detecta virus del VIH en las células, que han recibido un trasplante de celulas madre. |
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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 | 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 effects of eight intravenous infusions of 3BNC117 and 10-1074, each dosed at 30 mg/kg, on maintaining viral suppression under cART discontinuation in HIV+ participants with undetectable replication competent HIV reservoir after allogeneic stem cell transplantation in presence of cART. |
Evaluar los efectos de ocho infusiones intravenosas de 3BNC117 y 10-1074, cada una administrada a 30 mg / kg, en el mantenimiento de la supresión viral bajo la interrupción de TAR, en participantes VIH + con un reservorio viral competente indetectable después del trasplante alogénico de células madre en presencia de TAR. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of eight intravenous infusions of 3BNC117 and 10-1074, each dosed at 30 mg/kg, in HIV-infected individuals during first 8 months of ATI.
- To determine the serum levels of 3BNC117 and 10-1074 throughout the study. |
- Evaluar la seguridad y la tolerabilidad de ocho infusiones intravenosas de 3BNC117 y 10-1074, cada una dosificada a 30 mg / kg, en individuos infectados por el VIH durante los primeros 8 meses de la interrupción analítica del tratamiento (ATI).
- Determinar los niveles en suero de 3BNC117 y 10-1074 a lo largo del estudio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. More than 2 years post-HSCT 2. Being off immunosuppression for at least one year (related to allo-HSCT) 3. Undetectable levels of HIV replication competent reservoirs in blood (< 0,1 IUPM) 4. CD4 count levels higher than 200 cel/mm3. 5. Aged at least 18 years and not older than 65 at the day of screening 6. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. 7. In the opinion of the principal investigator or designee, the participant has understood the information provided and capable of giving written informed consent. 8. If heterosexually active female; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner1) from 14 days prior to the first bNAbs administration until at least 6 months after the last bNAbs administration; all female volunteers must be willing to undergo urine pregnancy tests at time points specified. 9. If heterosexually active male; willing to use an effective method of contraception (anatomical sterility in self) or agree on the use of an effective method of contraception by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility1) from the day of the first bNAbs administration until 6 months after the last bNAbs administration. 10. Willing to accept blood draws at time points specified. 11. Not sharing injection drug equipment, such as needles. |
1. Más de 2 años post-HSCT 2. No haber recibido inmunosupresión durante al menos un año (relacionadao con allo-HSCT) 3. Niveles indetectables de reservorios virales competentes en sangre (<0,1 IUPM). 4. Niveles de CD4 superiores a 200 cel/mm3. 5. Sujetos mayores de 18 años y no más de 65 en el día de la selección 6. Dispuestos a cumplir con los requisitos del protocolo y disponibles para su seguimiento durante la duración del estudio. 7. En opinión del investigador principal o su designado, el participante ha comprendido la información proporcionada y puede dar su consentimiento informado por escrito. 8. Si el participante es una mujer heterosexualmente activa; utilizar un método anticonceptivo eficaz (anticoncepción hormonal, dispositivo intrauterino (DIU) o esterilidad anatómica en si misma o en la pareja *) desde los 14 días anteriores a la primera administración de bNAbs hasta al menos 6 meses después de la última administración de bNAbs; todas las voluntarias deben estar dispuestas a someterse a pruebas de embarazo en orina en los momentos especificados en el Programa de Procedimientos. 9. Si el participante es un hombre heterosexualmente activo; dispuesto a utilizar un método anticonceptivo eficaz (esterilidad anatómica en sí mismo) o estar de acuerdo con el uso de un método anticonceptivo eficaz por parte de su pareja (anticoncepción hormonal, dispositivo intrauterino (DIU) o esterilidad anatómica *) desde el día de la primera administración de bNAbs hasta 6 meses después de la última administración de bNAbs. 10. Dispuesto a aceptar extracciones de sangre en los momentos especificados por protocolo. 11. No compartir material de inyección de drogas, como agujas. |
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E.4 | Principal exclusion criteria |
1. Pregnancy or lactating 2. Participation in another clinical trial within 12 weeks of study entry (at screening period). 3. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject’s ability to complete the study. |
1. Mujeres embarazadas o en periodo de lactancia. 2. Participación en otro ensayo clínico dentro de las 12 semanas posteriores a la inclusión en el estudio (en el período de selección). 3. Historia o manifestaciones clínicas de cualquier trastorno físico o psiquiátrico que pueda afectar la capacidad del sujeto para completar el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Time to reappearance of HIV-1 viremia (plasma HIV-1 RNA level > 50 copies/ml in 2 consecutive measurements) after ART interruption. - Time to reappearance of HIV-1 replication competent reservoir (determined by the number of infectious units per 10^6 CD4+ T cells (IUPM) using a viral outgrowth assay) after ART interruption. - Time to reappearance of HIV-1 total reservoir (determined by the number HIV-DNA copies per 10^6 CD4+ T cells) after ART interruption. |
- Tiempo de reaparición de la viremia del VIH-1 (HIV-1 RNA en plasma > 50 copias/ml en 2 determinaciones consecutivas) después de la interrupción del TAR. - Tiempo de reaparición de la capacidad de replicación del reservorio del VIH-1 (determinado por el número de unidades infecciosas por 106 células T CD4 + (IUPM) usando un ensayo de cultivo viral) después de la interrupción del TAR. - Tiempo de reaparición de VIH-1 en el reservorio total (determinado por el número de copias de ADN-VIH por 106 células T CD4 +) después de la interrupción del TAR. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The viral load is measured since the baseline to the end of the study, every 2 weeks. HIV-1 reservoir is measured since the baseline to the end of the study, every month. |
La carga vira se mide desde el inicio del estudio hasta el fin del estudio, cada 2 semanas. el reservorio de VIH-1 se mide desde el inicio del estudio hasta el fin del estudio, cada mes. |
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E.5.2 | Secondary end point(s) |
- Safety evaluation, as measured by rate and severity of adverse events (AE) and serious adverse events (SAE).
- Serum levels of 3BNC117 and 10-1074 throughout the study. |
- Evaluación de la seguridad, medida por la tasa y la gravedad de los acontecimientos adversos (AE) y los acontecimientos adversos graves (SAE). - Niveles en suero de 3BNC117 y 10-1074 a lo largo del estudio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As well as ad hoc reporting, safety and Serum levels of 3BNC117 and 10-1074 will be assessed at the following visits: - bNAbs administration visits: M1, M2, M3, M4, M5, M6, M7 AND M8. - Follow-up visits: M9, M10, M11, M12, M13, M14, M15, M16, M17. - End of study visit: M18 |
Además de los informes ad hoc, la seguridad y los niveles séricos 3BNC117 y 10-1074 se evaluarán en las siguientes visitas: - Visitas de administración de bNAbs: M1, M2, M3, M4, M5, M6, M7 Y M8. - Visitas de seguimiento: M9, M10, M11, M12, M13, M14, M15, M16, M17. - Visita de fin de estudio: M18. |
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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 | 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) | 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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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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LVLS (18 months visit in case of no cART resumption or 3 months after viral suppression visit in case of cART resumption) |
LVLS (visita a los 18 meses en caso de no reanudación del TAR o a los 3 meses después de la visita de supresión viral en caso de reanudarse el TAR) |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |