Estudo de Bictegravir/Lenacapavir em crianças e adolescentes com HIV-1
Um estudo aberto de fase 2/3 para avaliar a farmacocinética, segurança e atividade antiviral de Bictegravir/Lenacapavir em crianças e adolescentes com HIV-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.
Visão geral do estudo
Status
Condições
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
- Fase 3
Contactos e Locais
Locais de estudo
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Buenos Aires, Argentina, C1141ACG,
- Helios Salud S.A
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Madrid, Espanha, 28046
- Hospital Universitario La Paz
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Madrid, Espanha, 28007
- Hospital General Universitario Gregorio Marano
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Madrid, Espanha, 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, Itália, 20157
- ASST FBF Sacco Ospedale Sacco
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Roma, Itália, 00165
- IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
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Cape Town, África do Sul, 7505
- FAMCRU Ukwanda School for Rural Health
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Cape Town, África do Sul, 7646
- Be Part Yoluntu
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Durban, África do Sul, 3629
- Durban International Clinical Research Site, Enhancing Care Foundation
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East London, África do Sul, 5219
- Monti Clinical Research Centre
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Johannesburg, África do Sul, 1862
- Perinatal HIV Research Unit
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Johannesburg, África do Sul, 2038
- Wits RHI Shandukani Research Centre CRS
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Johannesburg, África do Sul, 2112
- Nkanyezi VIDA Research Unit
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Ka-Majosi, África do Sul, 944
- Khomanani Health Research and Wellness Centre
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KwaDukuza, África do Sul, 4449
- Clinical Research Institute of South Africa (CRISA)
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Pretoria, África do Sul, 0087
- The Aurum Institute: Pretoria Clinical Research Centre
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Soshanguve, África do Sul, 0152
- Setshaba Research Centre
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição sequencial
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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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
Outros nomes:
Tablets administered orally without regard to food
Outros nomes:
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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
Outros nomes:
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
Outros nomes:
Tablets administered orally without regard to food |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Porcentagem de participantes que experimentaram eventos adversos emergentes do tratamento (TEAEs) até a semana 24
Prazo: Data da primeira dose até a semana 24
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Data da primeira dose até a semana 24
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Porcentagem de participantes que apresentam anormalidades laboratoriais emergentes do tratamento até a semana 24
Prazo: Data da primeira dose até a semana 24
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Data da primeira dose até a semana 24
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PK Parameter: Cmax of BIC and LEN at Steady State
Prazo: 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
Prazo: 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
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Porcentagem de participantes que vivenciaram TEAEs até a semana 48
Prazo: Data da primeira dose até a semana 48
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Data da primeira dose até a semana 48
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Porcentagem de participantes que apresentam anormalidades laboratoriais emergentes do tratamento até a semana 48
Prazo: O primeiro data da semana 48
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O primeiro data da semana 48
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Proporção de participantes com RNA plasmático de HIV-1 < 50 cópias/mL e ≥ 50 cópias/mL na semana 24 com base no algoritmo de instantâneo definido pela Food and Drug Administration (FDA) dos Estados Unidos (EUA)
Prazo: Semana 24
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Semana 24
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Proporção de participantes com RNA plasmático de HIV-1 < 50 cópias/mL e ≥ 50 cópias/mL na semana 48 com base no algoritmo de instantâneo definido pela FDA dos Estados Unidos
Prazo: Semana 48
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Semana 48
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Alteração da linha de base em contagens de células de clusters de diferenciação 4 (CD4) na semana 24
Prazo: Linha de base, semana 24
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Linha de base, semana 24
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Alteração da linha de base na porcentagem de CD4 na semana 24
Prazo: Linha de base, semana 24
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Linha de base, semana 24
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Alteração da linha de base nas contagens de células CD4 na semana 48
Prazo: Linha de base, semana 48
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Linha de base, semana 48
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Alteração da linha de base na porcentagem de CD4 na semana 48
Prazo: Linha de base, semana 48
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Linha de base, semana 48
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PK Parameter: AUClast for BIC and LEN at Steady State
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
- Diretor de estudo: Gilead Study Director, Gilead Sciences
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- GS-US-621-6463
- 2023-509428-16 (Outro identificador: European Medicines Agency)
- 2023 (Concessão/Contrato do NIH dos EUA)
Plano para dados de participantes individuais (IPD)
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