Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1
- Registration Number
- NCT06517693
- Brief 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.
- Detailed Description
This is an open-label, phase I study of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) PGT121.414.LS alone and in combination with VRC07-523LS administered soon after birth in infants exposed to HIV-1. The study is designed to assess the safety and pharmacokinetics (PK) profile of one and two subcutaneous (SC) doses of PGT121.414.LS alone or in combination with VRC07-523LS through Week 12 and Week 24, respectively.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 48
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Birthing parent is of legal age or circumstance to provide independent informed consent and is willing and able to provide written informed consent for themselves and permission for their infant's participation in this study.
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Birthing parent has confirmed HIV-1 infection based on positive test results from two samples collected from two separate blood collection tubes.
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Infant was singleton or twin.
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Infant's gestational age at birth was at least 36 weeks.
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At birth, infant's weight was at least 2 kg.
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At entry, infant is less than 72 hours of age and is anticipated to receive study product within 72 hours after birth.
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At screening, infant has the following laboratory test results:
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Hemoglobin, normal or grade 1 (≥13 g/dL or ≥8.05 mmol/L)
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Platelets, normal or grade 1 (≥100,000 cells/mm3 or ≥100.000 x10^9 cells/L)
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Absolute neutrophil count (ANC), normal or grade 1
- ≤24 hours old (≥4,000 cells/mm3 or ≥4.000 x10^9 cells/L)
- >24 hours old (≥1,250 cells/mm3 or ≥1.250 x10^9 cells/L)
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Alanine transaminase (ALT), normal (<1.25 x ULN)
-
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At entry, infant is generally healthy as determined by the site investigator based on review of all available medical history information and physical examination findings.
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Cohorts 1 and 2, Strata BF only: At entry, infant is breastfeeding or the birthing parent has indicated an intention to initiate breastfeeding.
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Cohorts 1 and 2, Strata FF, only: At entry, infant is not breastfeeding and the birthing parent has indicated no intention to breastfeed.
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At entry, infant is at increased risk of HIV acquisition.
Cohorts 1 and 2, Strata FF only:
- Birthing parent had acute HIV during this pregnancy; or
- Birthing parent with detectable viral replication (plasma HIV RNA results at least 50 copies/mL) during pregnancy who did not have confirmed viral suppression, defined as at least two consecutive plasma HIV RNA results less than 50 copies/mL from specimens obtained at least four weeks apart with the latest result within four weeks prior to delivery; or
- Birthing parent not receiving appropriate ART for at least two weeks, with any part of the two-week period occurring within four weeks prior to delivery, based on birthing parent's report or available medical records.
Cohorts 1 and 2, BF only:
- Per birthing parent's report, intends to breastfeed
- Birthing parent has received any investigational product during this pregnancy.
- Infant has received any active or passive HIV immunotherapy or any investigational product.
- At entry, infant with a documented positive HIV Nucleic Acid Test (NAT) result.
- Birthing parent or infant has any condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 Stratum Formula Fed (FF) PGT121.414.LS Single subcutaneous (SC) dose of PGT121.414.LS at birth, based on weight. Cohort 2 Stratum BF VRC07-523LS Initial SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight. Second SC doses of 100 mg of PGT121.414.LS and 100 mg VRC07-523LS at Week 12, if still breastfeeding. Dosing at Week 12 is not based on weight. Cohort 2 Stratum FF PGT121.414.LS Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight. Cohort 2 Stratum BF PGT121.414.LS Initial SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight. Second SC doses of 100 mg of PGT121.414.LS and 100 mg VRC07-523LS at Week 12, if still breastfeeding. Dosing at Week 12 is not based on weight. Cohort 1 Stratum Breastfed (BF) PGT121.414.LS Initial SC dose of PGT121.414.LS at birth, based on weight. Second SC dose of 100 mg PGT121.414.LS at Week 12, if still breastfeeding. Dosing at Week 12 is not based on weight. Cohort 2 Stratum FF VRC07-523LS Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight.
- Primary Outcome Measures
Name Time Method PGT121.414.LS concentration at the end of the first dose interval (C(12WK)) (single/first dose) Week 12 PGT121.414.LS 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 concentration at the end of the first dose interval (C(12WK)) single/first dose) 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 area under the curve (AUC(0-12WK)) (single/first dose) Day 0 through Week 12 VRC07-523LS maximum concentration (Cmax) (single/first dose) Day 0 through Week 48 Proportion of infants with at least one Grade 3 or higher Adverse Event (AE) (one dose) Day 0 through Week 12 PGT121.414.LS time of maximum concentration (Tmax) (single/first dose) Day 0 through Week 48 PGT121.414.LS concentration at the end of the second dose interval (C(24WK)) (two doses) Week 24 VRC07-523LS concentration at the end of the second dose interval (C(24WK)) (two doses) Week 24 VRC07-523LS area under the curve (AUC(0-12WK)) Day 0 through Week 12
- Secondary Outcome Measures
Name Time Method 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 anti-PGT121.414.LS antibodies detected Week 48 Proportion of infants with anti-VRC07-523LS antibodies detected Week 48 PGT121.414.LS AUC(0-48WK) after single dose administration Week 48 PGT121.414.LS concentration after two dose administration Week 60 VRC07-523LS concentration after two dose administration Week 60 VRC07-523LS apparent clearance (CL/F) 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 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 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 VRC07-523LS half-life (T1/2) following tow dose administration Day 0 through Week 60 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 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 at least one Grade 2 or higher AE (two doses) Day 0 through Week 24 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 half-life (T1/2) following single dose administration Day 0 through Week 48 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 any AEs that lead to study product discontinuation Day 0 through Week 12 PGT121.414.LS concentration after single dose administration Week 48 Proportion of infants with confirmed HIV infection following receipt of study product Day 0 through Week 96
Trial Locations
- Locations (16)
Site 5129, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research
🇵🇷San Juan, Puerto Rico
Site 5030, Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Site 5112, David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Site 5052, University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Site 5127, Pediatric Perinatal HIV
🇺🇸Miami, Florida, United States
Site 5083, Rush University Cook County Hospital Chicago
🇺🇸Chicago, Illinois, United States
Site 5092, Johns Hopkins University Baltimore
🇺🇸Baltimore, Maryland, United States
Site 5114, Bronx-Lebanon Hospital Center
🇺🇸Bronx, New York, United States
Site 5013, Jacobi Medical Center Bronx
🇺🇸Bronx, New York, United States
Site 6501, St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Site 5097, Hospital Geral De Nova Iguacu Brazil
🇧🇷Rio De Janeiro, Brazil
Site 5051, University of Florida Jacksonville
🇺🇸Jacksonville, Florida, United States
Site 5128, Baylor College of Medicine/Texas Children's Hospital
🇺🇸Houston, Texas, United States
Site 5072, Hospital Federal dos Servidores do Estado
🇧🇷Rio De Janeiro, Brazil
Site 5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho
🇰🇪Kericho, Kenya
Site 8950, FAMCRU
🇿🇦Cape Town, Parrow Valley, South Africa