lenacapavir for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Participants must meet all of the following inclusion criteria to be eligible for participation in this study: Parent, guardian, or legally authorized representative willing and able to provide written informed consent prior to performing study procedures as required by local country regulations.\n- Lactating people must agree to discontinue nursing before administration of the study drugs.\n- Participant willing and able to provide written assent if possible (in accordance with their local institutional guidelines and local country regulations).\n- 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\n- On a complex ARV regimen. Complex regimens are any ART that is not a STR taken once daily (eg, > 1 tablet or any other formulation a day).\n- Documented plasma HIV-1 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).\n- Plasma HIV-1 RNA levels < 50 copies/mL at screening.\n- No documented or suspected resistance to INSTIs (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).\n- The following laboratory parameters at screening: a) Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 using Bedside Schwartz formula. b) Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3). c) Hemoglobin ≥ 85 g/L (> 8.5 g/dL). d) Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3). e) Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) ≤ 5 x upper limit of normal. f) Total bilirubin ≤ 23 µmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 µmol/L (≤ 0.4 mg/dL).\n- Negative serum beta-human chorionic gonadotropin pregnancy test at screening and a negative urine pregnancy test at Day 1 for participants assigned female at birth of childbearing potential only (as defined in Appendix 11.5)."}

Exclusion criteria

• {"criterion_text":"- Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study: CD4 cell count < 200 cells/mm3.\n- Acute hepatitis within 30 days prior to screening.\n- Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed).\n- 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.\n- A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).\n- Current alcohol or substance use judged by the investigator to potentially interfere with the participant’s study compliance.\n- Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.\n- Participation or planned participation in any other clinical study (including observational studies) without prior approval from the sponsor throughout the study.\n- Known hypersensitivity to the study drug, its metabolites, or formulation excipient.\n- Requirement for ongoing therapy with or prior use of any prohibited medications listed in Section 5.3.1.\n- CD4 percentage < 20%.\n- Life expectancy ≤ 1 year.\n- An opportunistic illness indicative of Stage 3 HIV diagnosed within 30 days prior to screening (as defined in Appendix 11.9).\n- Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening."}

Primary endpoints

• {"endpoint_text":"- Steady-state PK parameters (Cmax, AUCtau, and Ctau) of BIC and LEN","definition_or_measurement_approach":"Measurement of steady-state pharmacokinetic parameters (Cmax, AUCtau, Ctau) for bictegravir (BIC) and lenacapavir (LEN)."}
• {"endpoint_text":"- Proportion of participants experiencing treatment-emergent AEs through Week 24","definition_or_measurement_approach":"Proportion of participants with treatment-emergent adverse events assessed through Week 24."}
• {"endpoint_text":"- Proportion of participants experiencing treatment-emergent laboratory abnormalities through Week 24","definition_or_measurement_approach":"Proportion of participants with treatment-emergent laboratory abnormalities assessed through Week 24."}

Secondary endpoints

• {"endpoint_text":"- Steady-state PK parameters (AUClast, Ctrough, Tmax, Tlast, t1/2, CL, Vz, and λz) for BIC and LEN","definition_or_measurement_approach":"Measurement of additional steady-state PK parameters (AUClast, Ctrough, Tmax, Tlast, t1/2, clearance [CL], volume of distribution [Vz], and λz) for BIC and LEN."}
• {"endpoint_text":"- Proportion of participants experiencing treatment-emergent AEs through Week 48","definition_or_measurement_approach":"Proportion of participants with treatment-emergent adverse events assessed through Week 48."}
• {"endpoint_text":"- Proportion of participants experiencing treatment-emergent laboratory abnormalities through Week 48","definition_or_measurement_approach":"Proportion of participants with treatment-emergent laboratory abnormalities assessed through Week 48."}
• {"endpoint_text":"- Proportion of participants with plasma HIV-1 RNA < 50 copies/mL and ≥ 50 copies/mL at Weeks 24 and 48 based on the US Food and Drug Administration (FDA)-defined snapshot algorithm","definition_or_measurement_approach":"Proportion of participants achieving plasma HIV-1 RNA <50 copies/mL and those with ≥50 copies/mL at Weeks 24 and 48 using the FDA-defined snapshot algorithm."}
• {"endpoint_text":"- Change from baseline in CD4 cell counts and percentages at Weeks 24 and 48","definition_or_measurement_approach":"Change from baseline in absolute CD4 cell counts and CD4 percentages measured at Weeks 24 and 48."}
• {"endpoint_text":"- Acceptability and palatability summary of LEN oral loading dose at Day 1 and Day 2 assessed by questionnaire","definition_or_measurement_approach":"Acceptability and palatability assessed by participant/parent questionnaires for LEN oral loading dose at Day 1 and Day 2."}
• {"endpoint_text":"- Acceptability and palatability summary of oral BIC/LEN oral FDC at Day 1, Week 4, Week 24, and Week 48 assessed by questionnaire","definition_or_measurement_approach":"Acceptability and palatability assessed by participant/parent questionnaires for the BIC/LEN fixed-dose combination at Day 1, Week 4, Week 24, and Week 48."}

Spain

Earliest CTIS Part Ii Submission Date

23-07-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

547

Number Of Sites

3

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

599

Number Of Sites

2

Number Of Participants

5

Primary sponsor

Full Name

Gilead Sciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

QPS LLC

Responsibilities

code: 7

Name

PPD Development LP

Responsibilities

code: 1, code: 12, code: 13, code: 2, code: 5

Name

Medidata Solutions Inc.

Responsibilities

code: 7

Third parties

• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"code: 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"code: 1, code: 12, code: 13, code: 2, code: 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Monogram Biosciences Inc.","duties_or_roles":"HIV-1 proviral DNA sequencing; HIV-1 genotype/phenotype testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Bioanalytical analysis; Central Labs; code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Bioanalytical analysis; Central Labs; code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Institute of Immunology and Genetics","duties_or_roles":"HIV-1 proviral DNA sequencing; HIV-1 genotype/phenotype testing","organisation_type":"Health care"}