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

Phase 2

Recruiting

• Conditions: HIV-1-infection
• Interventions: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Optimized Background Regimen (OBR)

• Registration Number: NCT06749054
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-12-19
• Study First Submitted QC: 2024-12-19
• Study First Posted: 2024-12-27
• Study Start: 2025-03-26
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-09
• Primary Completion: 2026-06
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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:

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

Key

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LEN	Subcutaneous Lenacapavir	Participants will receive oral LEN 600 mg on Days 1 and 2. Participants will also receive 2 doses of LEN 927 mg as subcutaneous (SC) injection on Day 1 and Week 26 along with their OBR per clinical practice. At the Week 52, participants will be given the option to receive SC LEN every 6 months while continuing their OBR for at least another 2 SC LEN doses in the extension phase.
LEN	Optimized Background Regimen (OBR)	Participants will receive oral LEN 600 mg on Days 1 and 2. Participants will also receive 2 doses of LEN 927 mg as subcutaneous (SC) injection on Day 1 and Week 26 along with their OBR per clinical practice. At the Week 52, participants will be given the option to receive SC LEN every 6 months while continuing their OBR for at least another 2 SC LEN doses in the extension phase.
LEN	Oral Lenacapavir	Participants will receive oral LEN 600 mg on Days 1 and 2. Participants will also receive 2 doses of LEN 927 mg as subcutaneous (SC) injection on Day 1 and Week 26 along with their OBR per clinical practice. At the Week 52, participants will be given the option to receive SC LEN every 6 months while continuing their OBR for at least another 2 SC LEN doses in the extension phase.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter: Ctrough, W26 of Lenacapavir (LEN)	Week 26	Ctrough, W26 is defined as the plasma concentration at the end of the dosing interval at Week 26.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 26	First dose date up to Week 26
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 26	First dose date up to Week 26

Secondary Outcome Measures

Name	Time	Method
PK Parameter: Cmax, D1-W26 of LEN	Day 1 up to Week 26	Cmax, D1-W26 is defined as the maximum observed concentration of drug from Day 1 to Week 26.
PK Parameter: AUC D1-W26 of LEN	Day 1 up to Week 26	AUC D1-W26 is defined as the partial area under the concentration versus time curve from Day 1 to Week 26.
Percentage of Participants Experiencing Treatment-Emergent AEs Through Week 52	First dose date up to Week 52
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 52	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	Week 26
Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-Defined Snapshot Algorithm	Week 52
Change From Baseline in Clusters of Differentiation (CD4)+ Cell Counts at Week 26	Baseline, Week 26
Change From Baseline in CD4+ Cell Counts at Week 52	Baseline, Week 52
Percent Change From Baseline in CD4+ at Week 26	Baseline, Week 26
Percent Change From Baseline in CD4+ at Week 52	Baseline, Week 52
General Acceptability of Oral LEN as Assessed by Percentage of Participants With Acceptability Questionnaire Responses on Day 1	Day 1	To assess the acceptability of the study drug, the participants will complete questionnaire including a question on general acceptability of the assigned study drug on an ordinal 5-category scale.
General Acceptability of Oral LEN as Assessed by Percentage of Participants With Acceptability Questionnaire Responses on Day 2	Day 2	To assess the acceptability of the study drug, the participants will complete questionnaire including a question on general acceptability of the assigned study drug on an ordinal 5-category scale.
General Palatability of Oral LEN as Assessed by Percentage of Participants With Palatability Questionnaire Responses on Day 1	Day 1	To assess the palatability of the study drug, the participants will complete questionnaire including a question on general palatability of the assigned study drug on an ordinal 5-category scale.
General Palatability of Oral LEN as Assessed by Percentage of Participants With Palatability Questionnaire Responses on Day 2	Day 2	To assess the palatability of the study drug, the participants will complete questionnaire including a question on general palatability of the assigned study drug on an ordinal 5-category scale.

Trial Locations

Locations (7)

Rahima Moosa Mother and Child Hospital; 🇿🇦 Johannesburg, South Africa

Grady Health System, Ponce De Leon Center; 🇺🇸 Atlanta, Georgia, United States

FAMCRU; 🇿🇦 Cape Town, South Africa

Wits RHI Shandukani Research Centre CRS; 🇿🇦 Johannesburg, South Africa

Victoria Mxenge Hospital; 🇿🇦 KwaZulu - Natal, South Africa

Be Part Research Pty (Ltd); 🇿🇦 Paarl, South Africa

Perinatal HIV Research Unit (PHRU); 🇿🇦 Soweto, South Africa