Clinical trial NCT06532656: Study of Bictegravir/Lenacapavir in Children and Adolescents With HIV-1
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: HIV-1-infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2024-08-01
Enrollment: 75
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: PK Parameter: Cmax of BIC and LEN at Steady State
timeFrame: Day 1 up to Week 24, as appropriate
measure: PK Parameter: AUCtau of BIC and LEN at Steady State
timeFrame: Day 1 up to Week 24, as appropriate
measure: PK Parameter: Ctrough of BIC and LEN at Steady State
timeFrame: Day 1 up to Week 24, as appropriate
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) Through Week 24
timeFrame: First dose date up to Week 24
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24
timeFrame: First dose date up to Week 24
Secondary outcomes:
measure: PK Parameter: AUClast for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: PK Parameter: Tmax for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: PK Parameter: Tlast for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: PK Parameter: T1/2 for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: PK Parameter: CL for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: PK Parameter: Vz for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: PK Parameter: λz for BIC and LEN at Steady State
timeFrame: Day 1 up to Week 48, as appropriate
measure: Percentage of Participants Experiencing TEAEs Through Week 48
timeFrame: First dose date up to Week 48
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48
timeFrame: First does date up to Week 48
measure: 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
timeFrame: Week 24
measure: 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
timeFrame: Week 48
measure: Change from Baseline in Clusters of Differentiation 4 (CD4) Cell Counts at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in CD4 Percentage at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in CD4 Cell Counts at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline in CD4 Percentage at Week 48
timeFrame: Baseline, Week 48
measure: Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire
timeFrame: Day 1
measure: Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire
timeFrame: Day 2
measure: Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire
timeFrame: Day 1
measure: Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire
timeFrame: Week 4
measure: Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire
timeFrame: Week 24
measure: Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire
timeFrame: Week 48
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Grady Ponce de Leon Center
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Buenos Aires
country: Argentina
facility: Helios Salud S.A
city: Milano
country: Italy
facility: ASST FBF Sacco Ospedale Sacco
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
city: Cape Town
country: South Africa
facility: Be Part Yoluntu
city: Durban
country: South Africa
facility: Durban International Clinical Research Site, Enhancing Care Foundation
city: Johannesburg
country: South Africa
facility: Perinatal HIV Research Unit
city: Johannesburg
country: South Africa
facility: Wits RHI Shandukani Research Centre CRS
city: Pretoria
country: South Africa
facility: The Aurum Institute: Pretoria Clinical Research Centre
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre
city: Worcester
country: South Africa
facility: FAMCRU Ukwanda School for Rural Health
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marano
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: