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

Phase 1RecruitingNCT06517693

National Institute of Allergy and Infectious Diseases (NIAID)48 enrolled

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.

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

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

HIV-1

Interventions

PGT121.414.LSDRUG

Administered SC in the thigh

VRC07-523LSDRUG

Administered SC in the thigh

Eligibility

Sex: ALLMax age: 72 HoursHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (16)

Site 5112, David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Outcomes

Primary Outcomes

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

VRC07-523LS time of maximum concentration (Tmax) (single/first dose)

Central Contacts

Emily Brown

CONTACT

919-321-3806 embrown@fhi360.org

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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

PGT121.414.LS half-life (T1/2) following two dose administration

Time frame: Day 0 through Week 60

VRC07-523LS AUC(0-48WK) after single dose administration

Time frame: Week 48

VRC07-523LS concentration after single dose administration

Time frame: Week 48

VRC07-523LS concentration after two dose administration

Time frame: Week 60

VRC07-523LS apparent clearance (CL/F)

Time frame: Day 0 through Week 60

VRC07-523LS half-life (T1/2) following single dose administration

Time frame: Day 0 through Week 48

VRC07-523LS half-life (T1/2) following tow dose administration

Time frame: Day 0 through Week 60

Proportion of infants with PGT121.414.LS concentrations > 20 and > 50 mcg/mL following single/first dose administration

Time frame: Week 12

Proportion of infants with PGT121.414.LS concentrations > 20 and > 50 mcg/mL following two dose administration

Time frame: Week 24

Proportion of infants with VRC07-523LS concentrations > 10 and > 20 mcg/mL following single/first dose administration

Time frame: Week 12

Proportion of infants with PGT121.414.LS concentrations > 10 and > 20 mcg/mL following two dose administration

Time frame: Week 24

Proportion of infants with anti-PGT121.414.LS antibodies detected

Time frame: Week 24

Proportion of infants with anti-VRC07-523LS antibodies detected

Time frame: Week 24

Proportion of infants with anti-PGT121.414.LS antibodies detected

Time frame: Week 48

Proportion of infants with anti-VRC07-523LS antibodies detected

Time frame: Week 48

Proportion of infants with confirmed HIV infection following receipt of study product

Time frame: 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

Time frame: Day 0 through Week 13