Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1

Open-Label, Phase I Study of the Safety and Pharmacokinetics of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1

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.

Study Overview

• Status: Recruiting
• Conditions: HIV-1
• Intervention / Treatment: Drug: PGT121.414.LS; Drug: VRC07-523LS

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Emily Brown; Phone Number: 919-321-3806; Email: embrown@fhi360.org

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, CEP 20221-903
    • Not yet recruiting
    • Site 5072, Hospital Federal dos Servidores do Estado
  • Rio de Janeiro, Brazil, CEP 26030-380
    • Not yet recruiting
    • Site 5097, Hospital Geral De Nova Iguacu Brazil
• Kenya
  • Kericho, Kenya, 20200
    • Not yet recruiting
    • Site 5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Not yet recruiting
    • Site 32513, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research Network CRS
• South Africa
  • Parrow Valley
    • Cape Town, Parrow Valley, South Africa, 7505
      • Not yet recruiting
      • Site 8950, FAMCRU
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • Site 5112, David Geffen School of Medicine at UCLA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Site 5052, University of Colorado Denver
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • Site 5051, University of Florida Jacksonville
    • Miami, Florida, United States, 33136
      • Withdrawn
      • Site 5127, Pediatric Perinatal HIV
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Site 5030, Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Site 5083, Rush University Cook County Hospital Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Site 5092, Johns Hopkins University Baltimore
  • New York
    • The Bronx, New York, United States, 10457
      • Recruiting
      • Site 5114, Bronx-Lebanon Hospital Center
      • Contact: Martha Cavallo, A.N.P., C.R.N.P.; Phone Number: 718-960-1010; Email: mcavallo@bronxleb.org
    • The Bronx, New York, United States, 10461
      • Not yet recruiting
      • Site 5013, Jacobi Medical Center Bronx
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Not yet recruiting
      • Site 6501, St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Site 5128, Baylor College of Medicine/Texas Children's Hospital
• Zimbabwe
  • Harare, Zimbabwe
    • Not yet recruiting
    • Site 31890, Harare Family Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.
• Birthing parent has confirmed HIV-1 infection based on positive test results from two samples collected from two separate blood collection tubes.
• Infant was singleton or twin.
• Infant's gestational age at birth was at least 36 weeks.
• At birth, infant's weight was at least 2 kg.
• At entry, infant is less than 72 hours of age and is anticipated to receive study product within 72 hours after birth.

• At screening, infant has the following laboratory test results:

  • Hemoglobin, normal or grade 1 (≥13 g/dL or ≥8.05 mmol/L)
  • Platelets, normal or grade 1 (≥100,000 cells/mm3 or ≥100.000 x10^9 cells/L)

  • Absolute neutrophil count (ANC), normal or grade 1

    1. ≤24 hours old (≥4,000 cells/mm3 or ≥4.000 x10^9 cells/L)
    2. >24 hours old (≥1,250 cells/mm3 or ≥1.250 x10^9 cells/L)
  • Alanine transaminase (ALT), normal (<1.25 x ULN)
• 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.
• Cohorts 1 and 2, Strata BF only: At entry, infant is breastfeeding or the birthing parent has indicated an intention to initiate breastfeeding.
• Cohorts 1 and 2, Strata FF, only: At entry, infant is not breastfeeding and the birthing parent has indicated no intention to breastfeed.
• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Stratum Formula Fed (FF); Single subcutaneous (SC) dose of PGT121.414.LS at birth, based on weight.	Drug: PGT121.414.LS; Administered SC in the thigh
Experimental: Cohort 1 Stratum Breastfed (BF); 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.	Drug: PGT121.414.LS; Administered SC in the thigh
Experimental: Cohort 2 Stratum FF; Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight.	Drug: PGT121.414.LS; Administered SC in the thigh; Drug: VRC07-523LS; Administered SC in the thigh
Experimental: Cohort 2 Stratum BF; 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.	Drug: PGT121.414.LS; Administered SC in the thigh; Drug: VRC07-523LS; Administered SC in the thigh

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• 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)
• Investigators: Study Chair: Coleen Cunningham, University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: IMPAACT 2037; 38962 (Other Identifier: DAIDS Study ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.

IPD Sharing Access Criteria

With whom?

• Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.
• For what types of analyses?
• To achieve aims in the proposal approved by the IMPAACT Network.
• By what mechanism will data be made available?
• Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https:// www.impaactnetwork.org/ resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No