Estudio de bictegravir/lenacapavir en niños y adolescentes con VIH-1
Un estudio abierto de fase 2/3 para evaluar la farmacocinética, la seguridad y la actividad antiviral de bictegravir/lenacapavir en niños y adolescentes con VIH-1
The goal of this clinical study is to learn about the safety and tolerability of bictegravir (BIC)/lenacapavir (LEN) and to learn how the study drug interacts with the body in virologically suppressed (VS) children and adolescents with human immunodeficiency virus type 1 (HIV-1) on a stable and complex antiretroviral (ARV) regimen. The study will also assess the safe loading dose of LEN and pharmacokinetics (PK) of BIC/LEN.
The primary objectives of this study are:
- To evaluate the steady-state PK of BIC and LEN and confirm the dose of the LEN loading dose and BIC/LEN FDC in VS children and adolescents with HIV-1.
- To evaluate the safety and tolerability of BIC/LEN through Week 24 in VS children and adolescents with HIV-1.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Buenos Aires, Argentina, C1141ACG,
- Helios Salud S.A
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Madrid, España, 28046
- Hospital Universitario La Paz
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Madrid, España, 28007
- Hospital General Universitario Gregorio Marano
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Madrid, España, 28041
- Hospital Universitario 12 De Octubre
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District of Columbia
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Washington D.C., District of Columbia, Estados Unidos, 20010
- Children's National Hospital
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Florida
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Tampa, Florida, Estados Unidos, 33612
- University of South Florida
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Georgia
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Atlanta, Georgia, Estados Unidos, 30308
- Grady Ponce de Leon Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60614
- Ann and Robert H. Lurie Children's Hospital of Chicago
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Milan, Italia, 20157
- ASST FBF Sacco Ospedale Sacco
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Roma, Italia, 00165
- IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
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Cape Town, Sudáfrica, 7505
- FAMCRU Ukwanda School for Rural Health
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Cape Town, Sudáfrica, 7646
- Be Part Yoluntu
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Durban, Sudáfrica, 3629
- Durban International Clinical Research Site, Enhancing Care Foundation
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East London, Sudáfrica, 5219
- Monti Clinical Research Centre
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Johannesburg, Sudáfrica, 1862
- Perinatal HIV Research Unit
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Johannesburg, Sudáfrica, 2038
- Wits RHI Shandukani Research Centre CRS
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Johannesburg, Sudáfrica, 2112
- Nkanyezi VIDA Research Unit
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Ka-Majosi, Sudáfrica, 944
- Khomanani Health Research and Wellness Centre
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KwaDukuza, Sudáfrica, 4449
- Clinical Research Institute of South Africa (CRISA)
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Pretoria, Sudáfrica, 0087
- The Aurum Institute: Pretoria Clinical Research Centre
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Soshanguve, Sudáfrica, 0152
- Setshaba Research Centre
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Key Inclusion Criteria:
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Age and body weight at screening:
- Cohort 1: ≥ 12 years to < 18 years weighing ≥ 35 kg.
- Cohort 2: ≥ 6 years to < 12 years weighing ≥ 25 kg to < 35 kg.
- Cohort 3: ≥ 2 years to < 6 years weighing ≥ 10 kg to < 25 kg.
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On a complex ARV regimen. Complex regimens are any ARV therapy that is not a single-tablet regimen taken once daily (eg, > 1 tablet or any other formulation a day).
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Documented plasma HIV-1 ribonucleic acid (RNA) levels must be < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is < 50 copies/mL) in the last 6 months prior to screening (at least 1 measure prior to screening).
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Plasma HIV-1 RNA levels < 50 copies/mL at screening.
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No documented or suspected resistance to integrase strand transfer inhibitors (mutations T66A/I/K, E92G/Q/V, G118R, F121C/Y, G140R, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
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The following laboratory parameters at screening:
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Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 using the Bedside Schwartz formula.
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Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3).
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Hemoglobin ≥ 85 g/L (> 8.5 g/dL).
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Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3).
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Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase)
≤ 5 x upper limit of normal.
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Total bilirubin ≤ 23 μmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 μmol/L (≤ 0.4 mg/dL).
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Key Exclusion Criteria:
- CD4 cell count < 200 cells/mm^3.
- CD4 percentage < 20%.
- Life expectancy ≤ 1 year.
- An opportunistic illness indicative of Stage 3 HIV diagnosed within the 30 days prior to screening.
- Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening.
- Acute hepatitis within 30 days prior to screening.
- Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed).
- Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B virus (HBV) core antibody (antibody against hepatitis B core antigen [anti-HBc]) at screening. If a participant is negative for HBsAg and positive for anti-HBc but HBV DNA is undetectable, the participant may be enrolled.
- A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).Current alcohol or substance use judged by the investigator to potentially interfere with the participant's study compliance.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN TOS 75/50 mg FDC
Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN TOS 75/50 mg starting on Day 1 through Week 48. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
Otros nombres:
Tablets administered orally without regard to food
Otros nombres:
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Experimental: Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
Otros nombres:
Tablets administered orally without regard to food |
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Experimental: Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
Otros nombres:
Tablets administered orally without regard to food |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Porcentaje de participantes que experimentaron eventos adversos emergentes del tratamiento (TEAE) hasta la semana 24
Periodo de tiempo: Fecha de primera dosis hasta la semana 24
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Fecha de primera dosis hasta la semana 24
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Porcentaje de participantes que experimentaron anomalías de laboratorio surgidas del tratamiento hasta la semana 24
Periodo de tiempo: Fecha de primera dosis hasta la semana 24
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Fecha de primera dosis hasta la semana 24
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PK Parameter: Cmax of BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 24, as appropriate
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Cmax is defined as the maximum observed concentration of drug at steady state. |
Day 1 up to Week 24, as appropriate
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PK Parameter: AUCtau of BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 24, as appropriate
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AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state. |
Day 1 up to Week 24, as appropriate
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PK Parameter: Ctrough of BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 24, as appropriate
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Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state. |
Day 1 up to Week 24, as appropriate
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Porcentaje de participantes que experimentaron TEAE hasta la semana 48
Periodo de tiempo: Fecha de primera dosis hasta la Semana 48
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Fecha de primera dosis hasta la Semana 48
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Porcentaje de participantes que experimentaron anomalías de laboratorio surgidas del tratamiento hasta la semana 48
Periodo de tiempo: La primera fecha hasta la semana 48.
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La primera fecha hasta la semana 48.
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Proporción de participantes con ARN del VIH-1 en plasma <50 copias/ml y ≥ 50 copias/ml en la semana 24 según el algoritmo instantáneo definido por la Administración de Alimentos y Medicamentos (FDA) de los Estados Unidos (EE. UU.)
Periodo de tiempo: Semana 24
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Semana 24
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Proporción de participantes con ARN del VIH-1 en plasma <50 copias/ml y ≥ 50 copias/ml en la semana 48 según el algoritmo instantáneo definido por la FDA de los Estados Unidos
Periodo de tiempo: Semana 48
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Semana 48
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Cambio desde el inicio en los recuentos de células de los grupos de diferenciación 4 (CD4) en la semana 24
Periodo de tiempo: Línea de base, semana 24
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Línea de base, semana 24
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Cambio desde el inicio en el porcentaje de CD4 en la semana 24
Periodo de tiempo: Línea de base, semana 24
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Línea de base, semana 24
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Cambio desde el inicio en los recuentos de células CD4 en la semana 48
Periodo de tiempo: Línea de base, semana 48
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Línea de base, semana 48
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Cambio desde el inicio en el porcentaje de CD4 en la semana 48
Periodo de tiempo: Línea de base, semana 48
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Línea de base, semana 48
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PK Parameter: AUClast for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Tmax for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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Tmax is defined as the time (observed time point) of Cmax at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Tlast for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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Tlast is defined as the time (observed time point) of Clast at steady state. Clast is defined as the last measurable concentration (above the quantification limit). |
Day 1 up to Week 48, as appropriate
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PK Parameter: T1/2 for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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T1/2 is defined as the terminal elimination half-life at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: CL for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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Clearance (CL) is the volume of plasma cleared of drug over a specified time period, at a steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Vz for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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Volume of distribution (Vz) is defined as the extent to in which the drug is distributed in the body tissue, rather than the plasma, to produce the desired effects at a steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: λz for BIC and LEN at Steady State
Periodo de tiempo: Day 1 up to Week 48, as appropriate
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λz is defined as the terminal elimination rate constant, which determines the rate at which the drug will be eliminated from the body after it is absorbed and distributed at a steady state. |
Day 1 up to Week 48, as appropriate
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Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire
Periodo de tiempo: Day 1
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 1
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Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire
Periodo de tiempo: Day 2
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 2
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Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire
Periodo de tiempo: Day 1
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 1
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire
Periodo de tiempo: Week 4
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 4
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire
Periodo de tiempo: Week 24
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 24
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire
Periodo de tiempo: Week 48
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 48
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Gilead Study Director, Gilead Sciences
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- GS-US-621-6463
- 2023-509428-16 (Otro identificador: European Medicines Agency)
- 2023 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .