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

Official title

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

Overview

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.

Interventions

• Drug PGT121.414.LS
  Administered SC in the thigh
• Drug VRC07-523LS
  Administered SC in the thigh

Primary outcome measures

• Proportion of infants with at least one Grade 3 or higher Adverse Event (AE) (one dose) [Time frame: 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) [Time frame: Day 0 through Week 12]
• Proportion of infants with at least one Grade 3 or higher AE (two doses) [Time frame: 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) [Time frame: Day 0 through Week 24]
• PGT121.414.LS maximum concentration (Cmax) (single/first dose) [Time frame: Day 0 through Week 48]
• PGT121.414.LS time of maximum concentration (Tmax) (single/first dose) [Time frame: Day 0 through Week 48]
• PGT121.414.LS area under the curve (AUC(0-12WK)) (single/first dose) [Time frame: Day 0 through Week 12]
• PGT121.414.LS concentration at the end of the first dose interval (C(12WK)) (single/first dose) [Time frame: Week 12]
• PGT121.414.LS concentration at the end of the second dose interval (C(24WK)) (two doses) [Time frame: Week 24]
• VRC07-523LS maximum concentration (Cmax) (single/first dose) [Time frame: Day 0 through Week 48]

Secondary outcome measures (12)

• Proportion of infants with at least one Grade 3 or higher AE [Time frame: Day 0 through Week 96]
• Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product [Time frame: Day 0 through Week 96]
• Proportion of infants with at least one Grade 2 or higher AE (one dose) [Time frame: 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) [Time frame: Day 0 through Week 12]
• Proportion of infants with at least one Grade 2 or higher AE (two doses) [Time frame: 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) [Time frame: Day 0 through Week 24]
• Proportion of infants with any AEs that lead to study product discontinuation [Time frame: Day 0 through Week 12]
• PGT121.414.LS AUC(0-48WK) after single dose administration [Time frame: Week 48]
• PGT121.414.LS concentration after single dose administration [Time frame: Week 48]
• PGT121.414.LS concentration after two dose administration [Time frame: Week 60]
• PGT121.414.LS apparent clearance (CL/F) [Time frame: Day 0 through Week 60]
• PGT121.414.LS half-life (T1/2) following single dose administration [Time frame: Day 0 through Week 48]

Eligibility criteria

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

• ≤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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 11 centers

• Site 5112, David Geffen School of Medicine at UCLA — Los Angeles
• Site 5052, University of Colorado Denver — Aurora
• Site 5051, University of Florida Jacksonville — Jacksonville
• Site 5127, Pediatric Perinatal HIV — Miami
• Site 5030, Emory University School of Medicine — Atlanta
• Site 5083, Rush University Cook County Hospital Chicago — Chicago
• Site 5092, Johns Hopkins University Baltimore — Baltimore
• Site 5114, Bronx-Lebanon Hospital Center — The Bronx
• … and 3 more centers

Brazil · 2 centers

• Site 5072, Hospital Federal dos Servidores do Estado — Rio de Janeiro
• Site 5097, Hospital Geral De Nova Iguacu Brazil — Rio de Janeiro

Kenya · 1 center

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

Puerto Rico · 1 center

• Site 32513, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research Network CRS — San Juan

South Africa · 1 center

• Site 8950, FAMCRU — Cape Town

Zimbabwe · 1 center

• Site 31890, Harare Family Care — Harare

Identifiers

NCT: NCT06517693 · IMPAACT 2037 · 38962

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗