Study of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1
- Registration Number
- NCT06532656
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this clinical study is to learn about the safety and tolerability of bictegravir/lenacapavir (BIC/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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
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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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg Lenacapavir 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. Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 75/50 mg FDC BIC/LEN FDC Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN 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. Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg Lenacapavir 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. Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg BIC/LEN FDC 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. Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg BIC/LEN FDC 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. Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 75/50 mg FDC Lenacapavir Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN 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.
- Primary Outcome Measures
Name Time Method PK Parameter: Cmax of BIC and LEN at Steady State Day 1 up to Week 24, as appropriate Cmax is defined as the maximum observed concentration of drug at steady state.
PK Parameter: AUCtau of BIC and LEN at Steady State Day 1 up to Week 24, as appropriate AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state.
PK Parameter: Ctrough of BIC and LEN at Steady State Day 1 up to Week 24, as appropriate Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 24 First dose date up to Week 24 Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24 First dose date up to Week 24
- Secondary Outcome Measures
Name Time Method PK Parameter: Vz for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate 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.
PK Parameter: λz for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate 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.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48 First does date up to Week 48 Proportion of Participants With Plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Week 48 Based on the United States FDA-Defined Snapshot Algorithm Week 48 PK Parameter: Tlast for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate 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).
PK Parameter: CL for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate Clearance (CL) is the volume of plasma cleared of drug over a specified time period, at a steady state.
Percentage of Participants Experiencing TEAEs Through Week 48 First dose date up to Week 48 Change from Baseline in Clusters of Differentiation 4 (CD4) Cell Counts at Week 24 Baseline, Week 24 Change from Baseline in CD4 Cell Counts at Week 48 Baseline, Week 48 Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire Week 4 Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.
Proportion of Participants With Plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Week 24 Based on the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm Week 24 Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire Day 2 Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.
Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire Day 1 Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.
PK Parameter: AUClast for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration at steady state.
PK Parameter: T1/2 for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate T1/2 is defined as the terminal elimination half-life at steady state.
PK Parameter: Tmax for BIC and LEN at Steady State Day 1 up to Week 48, as appropriate Tmax is defined as the time (observed time point) of Cmax at steady state.
Change from Baseline in CD4 Percentage at Week 24 Baseline, Week 24 Change from Baseline in CD4 Percentage at Week 48 Baseline, Week 48 Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire Week 24 Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.
Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire Week 48 Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.
Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire Day 1 Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.
Trial Locations
- Locations (17)
Children's National Hospital
🇺🇸Washington, District of Columbia, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Grady Ponce de Leon Center
🇺🇸Atlanta, Georgia, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Helios Salud S.A
🇦🇷Buenos Aires, Argentina
ASST FBF Sacco Ospedale Sacco
🇮🇹Milano, Italy
IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
🇮🇹Roma, Italy
Be Part Yoluntu
🇿🇦Cape Town, South Africa
Durban International Clinical Research Site, Enhancing Care Foundation
🇿🇦Durban, South Africa
Perinatal HIV Research Unit
🇿🇦Johannesburg, South Africa
Wits RHI Shandukani Research Centre CRS
🇿🇦Johannesburg, South Africa
The Aurum Institute: Pretoria Clinical Research Centre
🇿🇦Pretoria, South Africa
Setshaba Research Centre
🇿🇦Soshanguve, South Africa
FAMCRU Ukwanda School for Rural Health
🇿🇦Worcester, South Africa
Hospital General Universitario Gregorio Marano
🇪🇸Madrid, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain