Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1
NCT Number: NCT06517693
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: HIV-1
Interventions: DRUG: PGT121.414.LS|DRUG: VRC07-523LS
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|National Institute of Mental Health (NIMH)|National Institute of Allergy and Infectious Diseases Vaccine Research Center
Sex: ALL
Age: CHILD
Enrollment: 48
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-11-01
Completion Date: 2027-11-30
Locations: Site 5112, David Geffen School of Medicine at UCLA, Los Angeles, California, 90095, United States|Site 5052, University of Colorado Denver, Aurora, Colorado, 80045, United States|Site 5055, South Florida CDTC Ft Lauderdale, Fort Lauderdale, Florida, 33316, United States|Site 5051, University of Florida Jacksonville, Jacksonville, Florida, 32209, United States|Site 5127, Pediatric Perinatal HIV, Miami, Florida, 33136, United States|Site 5030, Emory School of Medicine, Atlanta, Georgia, 30322, United States|Site 5083, Rush University Cook County Hospital Chicago, Chicago, Illinois, 60612, United States|Site 5092, Johns Hopkins University Baltimore, Baltimore, Maryland, 21287, United States|Site 5114, Bronx-Lebanon Hospital Center, Bronx, New York, 10457, United States|Site 5013, Jacobi Medical Center Bronx, Bronx, New York, 10461, United States|Site 6501, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States|Site 5128, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas, 77030, United States|Site 5097, Hospital Geral De Nova Iguacu Brazil, Rio De Janeiro, RJ, CEP 26030-380, Brazil|Site 5072, Hospital Federal dos Servidores do Estado, Rio De Janeiro, CEP 20221-903, Brazil|Site 5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho, Kericho, 20200, Kenya|Site 5129, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research, San Juan, 00935, Puerto Rico|Site 8950, FAMCRU, Cape Town, Parrow Valley, 7505, South Africa

Summary:
The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) PGT121.414.LS alone and in combination with VRC07-523LS soon after birth in infants exposed to HIV-1.

Primary Outcome Measures: Proportion of infants with at least one Grade 3 or higher Adverse Event (AE) (one dose), Day 0 through Week 12|Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product (one dose), Day 0 through Week 12|Proportion of infants with at least one Grade 3 or higher AE (two doses), Day 0 through Week 24|Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product (two doses), Day 0 through Week 24|PGT121.414.LS maximum concentration (Cmax) (single/first dose), Day 0 through Week 48|PGT121.414.LS time of maximum concentration (Tmax) (single/first dose), Day 0 through Week 48|PGT121.414.LS area under the curve (AUC(0-12WK)) (single/first dose), Day 0 through Week 12|PGT121.414.LS concentration at the end of the first dose interval (C(12WK)) (single/first dose), Week 12|PGT121.414.LS concentration at the end of the second dose interval (C(24WK)) (two doses), Week 24|VRC07-523LS maximum concentration (Cmax) (single/first dose), Day 0 through Week 48|VRC07-523LS time of maximum concentration (Tmax) (single/first dose), Day 0 through Week 48|VRC07-523LS area under the curve (AUC(0-12WK)), Day 0 through Week 12|VRC07-523LS concentration at the end of the first dose interval (C(12WK)) single/first dose), Week 12|VRC07-523LS concentration at the end of the second dose interval (C(24WK)) (two doses), Week 24
Secondary Outcome Measures: Proportion of infants with at least one Grade 3 or higher AE, Day 0 through Week 96|Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product, Day 0 through Week 96|Proportion of infants with at least one Grade 2 or higher AE (one dose), Day 0 through Week 12|Proportion of infants with at least one Grade 2 or higher AE assessed as related to study product (one dose), Day 0 through Week 12|Proportion of infants with at least one Grade 2 or higher AE (two doses), Day 0 through Week 24|Proportion of infants with at least one Grade 2 or higher AE assessed as related to study product (two doses), Day 0 through Week 24|Proportion of infants with any AEs that lead to study product discontinuation, Day 0 through Week 12|PGT121.414.LS AUC(0-48WK) after single dose administration, Week 48|PGT121.414.LS concentration after single dose administration, Week 48|PGT121.414.LS concentration after two dose administration, Week 60|PGT121.414.LS apparent clearance (CL/F), Day 0 through Week 60|PGT121.414.LS half-life (T1/2) following single dose administration, Day 0 through Week 48|PGT121.414.LS half-life (T1/2) following two dose administration, Day 0 through Week 60|VRC07-523LS AUC(0-48WK) after single dose administration, Week 48|VRC07-523LS concentration after single dose administration, Week 48|VRC07-523LS concentration after two dose administration, Week 60|VRC07-523LS apparent clearance (CL/F), Day 0 through Week 60|VRC07-523LS half-life (T1/2) following single dose administration, Day 0 through Week 48|VRC07-523LS half-life (T1/2) following tow dose administration, Day 0 through Week 60|Proportion of infants with PGT121.414.LS concentrations > 20 and > 50 mcg/mL following single/first dose administration, Week 12|Proportion of infants with PGT121.414.LS concentrations > 20 and > 50 mcg/mL following two dose administration, Week 24|Proportion of infants with VRC07-523LS concentrations > 10 and > 20 mcg/mL following single/first dose administration, Week 12|Proportion of infants with PGT121.414.LS concentrations > 10 and > 20 mcg/mL following two dose administration, Week 24|Proportion of infants with anti-PGT121.414.LS antibodies detected, Week 24|Proportion of infants with anti-VRC07-523LS antibodies detected, Week 24|Proportion of infants with anti-PGT121.414.LS antibodies detected, Week 48|Proportion of infants with anti-VRC07-523LS antibodies detected, Week 48|Proportion of infants with confirmed HIV infection following receipt of study product, Day 0 through Week 96|Frequency of study product injection site local reactions for one and two SC doses of PGT121.414.LS alone or in combination with VRC07-523LS, Day 0 through Week 13