Evaluation of Long-Acting Lenacapavir for the Treatment of HIV-1 in Treatment-experienced Adolescents and Children

Official title

A Phase 2, Open-label, Single-Arm Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Antiviral Activity of Long-Acting Lenacapavir in Combination With an Optimized Background Regimen in Treatment-experienced Adolescents and Children With HIV-1

Overview

The goal of this clinical study is to learn more about the study drug, lenacapavir (LEN). The study will assess the safety, tolerability, and efficacy of long-acting LEN when combined with other medicines in adolescents and children living with HIV-1 who weigh at least 35 kg and have been treated before for HIV-1. The study will also see how easy it is for participants to take LEN as injection or an oral pill. The primary objectives are to evaluate the pharmacokinetics and safety of LEN in combination with optimized background regimen (OBR) in TE pediatric participants with HIV-1.

Interventions

• Drug Oral Lenacapavir
  Tablets administered without regard to food
• Drug Subcutaneous Lenacapavir
  Administered via subcutaneous injections
• Drug Optimized Background Regimen (OBR)
  Optimized background regimen as prescribed by the Investigator

Primary outcome measures

• Pharmacokinetic (PK) Parameter: Ctrough, W26 of Lenacapavir (LEN) [Time frame: Week 26]
• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 26 [Time frame: First dose date up to Week 26]
• Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 26 [Time frame: First dose date up to Week 26]

Secondary outcome measures (12)

• PK Parameter: Cmax, D1-W26 of LEN [Time frame: Day 1 up to Week 26]
• PK Parameter: AUC D1-W26 of LEN [Time frame: Day 1 up to Week 26]
• Percentage of Participants Experiencing Treatment-Emergent AEs Through Week 52 [Time frame: First dose date up to Week 52]
• Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 52 [Time frame: First dose date up to Week 52]
• Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm [Time frame: Week 26]
• Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-Defined Snapshot Algorithm [Time frame: Week 52]
• Change From Baseline in Clusters of Differentiation (CD4)+ Cell Counts at Week 26 [Time frame: Baseline, Week 26]
• Change From Baseline in CD4+ Cell Counts at Week 52 [Time frame: Baseline, Week 52]
• Percent Change From Baseline in CD4+ at Week 26 [Time frame: Baseline, Week 26]
• Percent Change From Baseline in CD4+ at Week 52 [Time frame: Baseline, Week 52]
• General Acceptability of Oral LEN as Assessed by Percentage of Participants With Acceptability Questionnaire Responses on Day 1 [Time frame: Day 1]
• General Acceptability of Oral LEN as Assessed by Percentage of Participants With Acceptability Questionnaire Responses on Day 2 [Time frame: Day 2]

Eligibility criteria

Inclusion criteria

• Body weight at screening ≥ 35 kg.
• On a stable failing antiretroviral (ARV) regimen for > 8 weeks before screening and willing to continue the regimen until Day 1.
• Plasma HIV-1 RNA ≥ 400 copies/mL on at least 2 consecutive occasions spanning at least 6 months, including at screening.
• Have previously changed their ARV regimen due to treatment failure.
• ARV treatment options limited due to resistance, tolerability, contraindications, safety, drug access.
• Able and willing to commit to taking LEN in combination with their OBR.
• The following laboratory parameters at screening:

• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 using Bedside Schwartz Formula.
• Absolute neutrophil count > 0.50 GI/L (> 500 cells/mm\^3).
• Hemoglobin ≥ 85 g/L (> 8.5 g/dL).
• Platelets ≥ 50 GI/L (≥ 50,000/mm\^3).
• Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 5 × upper limit of normal.
• Total bilirubin ≤ 23 μmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 μmol/L (≤ 0.4 mg/dL).

Exclusion criteria

• Life expectancy ≤ 1 year.
• An opportunistic illness requiring treatment within the 30 days prior to screening.
• Evidence of active pulmonary or extra-pulmonary tuberculosis within 3 months prior to screening.
• Hepatitis C virus (HCV) antibody positive with detectable HCV RNA at screening.
• Hepatitis B virus (HBV) surface antigen (HBsAg) positive or HBV core antibody (antibody against hepatitis B core antigen (anti-HBc)) positive; if individual is HBsAg negative and anti-HBc positive but HBV DNA undetectable, individual may be enrolled.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

South Africa · 8 centers

• FAMCRU — Cape Town
• CRISMO Research Centre — Germiston
• Wits RHI Shandukani Research Centre CRS — Johannesburg
• Rahima Moosa Mother and Child Hospital — Johannesburg
• Clinical Research Institute of South Africa (CRISA) — KwaDukuza
• Durban International Clinical Research Site, Enhancing Care Foundation — KwaZulu - Natal
• Be Part Research Pty (Ltd) — Paarl
• Perinatal HIV Research Unit (PHRU) — Soweto

United States · 1 center

• Grady Health System, Ponce De Leon Center — Atlanta

Identifiers

NCT: NCT06749054 · GS-US-200-6712

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗