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

NCT06517693 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IMPAACT 203738962
• Study Type: interventional
• Target: 48
• Locations: 6 countries
• Sites: 17

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.

Conditions

HIV-1

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (29)

• 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

Study Arms (4)

Cohort 1 Stratum Formula Fed (FF)

EXPERIMENTAL

Single subcutaneous (SC) dose of PGT121.414.LS at birth, based on weight.

Drug: PGT121.414.LS

Cohort 1 Stratum Breastfed (BF)

EXPERIMENTAL

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

Cohort 2 Stratum FF

EXPERIMENTAL

Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight.

Drug: PGT121.414.LS; Drug: VRC07-523LS

Cohort 2 Stratum BF

EXPERIMENTAL

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; Drug: VRC07-523LS

Interventions

PGT121.414.LS DRUG

Administered SC in the thigh

Cohort 1 Stratum Breastfed (BF); Cohort 1 Stratum Formula Fed (FF); Cohort 2 Stratum BF; Cohort 2 Stratum FF

VRC07-523LS DRUG

Administered SC in the thigh

Cohort 2 Stratum BF; Cohort 2 Stratum FF

Eligibility Criteria

• Age: Up to 72 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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
• ≤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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (17)

Site 5112, David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

NOT YET RECRUITING

Site 5052, University of Colorado Denver

Aurora, Colorado, 80045, United States

RECRUITING

Site 5051, University of Florida Jacksonville

Jacksonville, Florida, 32209, United States

RECRUITING

Site 5127, Pediatric Perinatal HIV

Miami, Florida, 33136, United States

WITHDRAWN

Site 5030, Emory University School of Medicine

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Site 5083, Rush University Cook County Hospital Chicago

Chicago, Illinois, 60612, United States

NOT YET RECRUITING

Site 5092, Johns Hopkins University Baltimore

Baltimore, Maryland, 21287, United States

RECRUITING

Site 5114, Bronx-Lebanon Hospital Center

The Bronx, New York, 10457, United States

RECRUITING

Site 5013, Jacobi Medical Center Bronx

The Bronx, New York, 10461, United States

NOT YET RECRUITING

Site 6501, St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

NOT YET RECRUITING

Site 5128, Baylor College of Medicine/Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Site 5072, Hospital Federal dos Servidores do Estado

Rio de Janeiro, CEP 20221-903, Brazil

NOT YET RECRUITING

Site 5097, Hospital Geral De Nova Iguacu Brazil

Rio de Janeiro, CEP 26030-380, Brazil

NOT YET RECRUITING

Site 5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho

Kericho, 20200, Kenya

NOT YET RECRUITING

Site 32513, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research Network CRS

San Juan, 00935, Puerto Rico

NOT YET RECRUITING

Site 8950, FAMCRU

Cape Town, Parrow Valley, 7505, South Africa

NOT YET RECRUITING

Site 31890, Harare Family Care

Harare, Zimbabwe

NOT YET RECRUITING

Study Officials

• Coleen Cunningham

  University of California, Irvine

  STUDY CHAIR

Central Study Contacts

Emily Brown

CONTACT

919-321-3806; embrown@fhi360.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: July 24, 2024
• Study Start: January 5, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

KE (1); ZA (1); US (11); BR (2); ZI (1); PR (1)