Study of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1

A Phase 2/3, Open-Label Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Lenacapavir; Drug: BIC/LEN FDC

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1141ACG,
    • Helios Salud S.A
• Italy
  • Milan, Italy, 20157
    • ASST FBF Sacco Ospedale Sacco
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
• South Africa
  • Cape Town, South Africa, 7505
    • FAMCRU Ukwanda School for Rural Health
  • Cape Town, South Africa, 7646
    • Be Part Yoluntu
  • Durban, South Africa, 3629
    • Durban International Clinical Research Site, Enhancing Care Foundation
  • East London, South Africa, 5219
    • Monti Clinical Research Centre
  • Johannesburg, South Africa, 1862
    • Perinatal HIV Research Unit
  • Johannesburg, South Africa, 2038
    • Wits RHI Shandukani Research Centre CRS
  • Johannesburg, South Africa, 2112
    • Nkanyezi VIDA Research Unit
  • Ka-Majosi, South Africa, 944
    • Khomanani Health Research and Wellness Centre
  • KwaDukuza, South Africa, 4449
    • Clinical Research Institute of South Africa (CRISA)
  • Pretoria, South Africa, 0087
    • The Aurum Institute: Pretoria Clinical Research Centre
  • Soshanguve, South Africa, 0152
    • Setshaba Research Centre
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marano
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Grady Ponce de Leon Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Ann and Robert H. Lurie Children's Hospital of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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.
• 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).
• 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).
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• 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).

• The following laboratory parameters at screening:

  • Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 using the Bedside Schwartz formula.
  • Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3).
  • Hemoglobin ≥ 85 g/L (> 8.5 g/dL).
  • Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3).

  • Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase)

    ≤ 5 x upper limit of normal.

  • Total bilirubin ≤ 23 μmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 μmol/L (≤ 0.4 mg/dL).

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN 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 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.	Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: BIC/LEN FDC; Tablets administered orally without regard to food
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.	Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: BIC/LEN FDC; Tablets administered orally without regard to food
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.	Drug: Lenacapavir; Tablets administered orally without regard to food; Other Names: GS-6207; Drug: BIC/LEN FDC; Tablets administered orally without regard to food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
PK Parameter: Cmax of BIC and LEN at Steady State	Cmax is defined as the maximum observed concentration of drug at steady state.	Day 1 up to Week 24, as appropriate
PK Parameter: AUCtau of BIC and LEN at Steady State	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
PK Parameter: Ctrough of BIC and LEN at Steady State	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter: AUClast for BIC and LEN at Steady State	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
PK Parameter: Tmax for BIC and LEN at Steady State	Tmax is defined as the time (observed time point) of Cmax at steady state.	Day 1 up to Week 48, as appropriate
PK Parameter: Tlast for BIC and LEN at Steady State	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
PK Parameter: T1/2 for BIC and LEN at Steady State	T1/2 is defined as the terminal elimination half-life at steady state.	Day 1 up to Week 48, as appropriate
PK Parameter: CL for BIC and LEN at Steady State	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
PK Parameter: Vz for BIC and LEN at Steady State	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
PK Parameter: λz for BIC and LEN at Steady State	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
Percentage of Participants Experiencing TEAEs Through Week 48		First dose date up to Week 48
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 24 Based on the United States (US) Food and Drug Administration (FDA)-Defined Snapshot Algorithm		Week 24
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
Change from Baseline in Clusters of Differentiation 4 (CD4) Cell Counts at Week 24		Baseline, Week 24
Change from Baseline in CD4 Percentage at Week 24		Baseline, Week 24
Change from Baseline in CD4 Cell Counts at Week 48		Baseline, Week 48
Change from Baseline in CD4 Percentage at Week 48		Baseline, Week 48
Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire	Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.	Day 1
Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire	Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.	Day 2
Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire	Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.	Day 1
Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire	Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.	Week 4
Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire	Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.	Week 24
Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire	Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability.	Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2024
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: lenacapavir
• Other Study ID Numbers: GS-US-621-6463; 2023-509428-16 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No