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.

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.