Clinical trial NCT06517693: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: HIV-1
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Mental Health (NIMH)
name: National Institute of Allergy and Infectious Diseases Vaccine Research Center (NIAID VRC)
First posted: 2024-07-24
Enrollment: 48
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.

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

    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.

Primary outcomes:
measure: Proportion of infants with at least one Grade 3 or higher Adverse Event (AE) (one dose)
timeFrame: Day 0 through Week 12
measure: Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product (one dose)
timeFrame: Day 0 through Week 12
measure: Proportion of infants with at least one Grade 3 or higher AE (two doses)
timeFrame: Day 0 through Week 24
measure: Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product (two doses)
timeFrame: Day 0 through Week 24
measure: PGT121.414.LS maximum concentration (Cmax) (single/first dose)
timeFrame: Day 0 through Week 48
measure: PGT121.414.LS time of maximum concentration (Tmax) (single/first dose)
timeFrame: Day 0 through Week 48
measure: PGT121.414.LS area under the curve (AUC(0-12WK)) (single/first dose)
timeFrame: Day 0 through Week 12
measure: PGT121.414.LS concentration at the end of the first dose interval (C(12WK)) (single/first dose)
timeFrame: Week 12
measure: PGT121.414.LS concentration at the end of the second dose interval (C(24WK)) (two doses)
timeFrame: Week 24
measure: VRC07-523LS maximum concentration (Cmax) (single/first dose)
timeFrame: Day 0 through Week 48
measure: VRC07-523LS time of maximum concentration (Tmax) (single/first dose)
timeFrame: Day 0 through Week 48
measure: VRC07-523LS area under the curve (AUC(0-12WK))
timeFrame: Day 0 through Week 12
measure: VRC07-523LS concentration at the end of the first dose interval (C(12WK)) single/first dose)
timeFrame: Week 12
measure: VRC07-523LS concentration at the end of the second dose interval (C(24WK)) (two doses)
timeFrame: Week 24
Secondary outcomes:
measure: Proportion of infants with at least one Grade 3 or higher AE
timeFrame: Day 0 through Week 96
measure: Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product
timeFrame: Day 0 through Week 96
measure: Proportion of infants with at least one Grade 2 or higher AE (one dose)
timeFrame: Day 0 through Week 12
measure: Proportion of infants with at least one Grade 2 or higher AE assessed as related to study product (one dose)
timeFrame: Day 0 through Week 12
measure: Proportion of infants with at least one Grade 2 or higher AE (two doses)
timeFrame: Day 0 through Week 24
measure: Proportion of infants with at least one Grade 2 or higher AE assessed as related to study product (two doses)
timeFrame: Day 0 through Week 24
measure: Proportion of infants with any AEs that lead to study product discontinuation
timeFrame: Day 0 through Week 12
measure: PGT121.414.LS AUC(0-48WK) after single dose administration
timeFrame: Week 48
measure: PGT121.414.LS concentration after single dose administration
timeFrame: Week 48
measure: PGT121.414.LS concentration after two dose administration
timeFrame: Week 60
measure: PGT121.414.LS apparent clearance (CL/F)
timeFrame: Day 0 through Week 60
measure: PGT121.414.LS half-life (T1/2) following single dose administration
timeFrame: Day 0 through Week 48
measure: PGT121.414.LS half-life (T1/2) following two dose administration
timeFrame: Day 0 through Week 60
measure: VRC07-523LS AUC(0-48WK) after single dose administration
timeFrame: Week 48
measure: VRC07-523LS concentration after single dose administration
timeFrame: Week 48
measure: VRC07-523LS concentration after two dose administration
timeFrame: Week 60
measure: VRC07-523LS apparent clearance (CL/F)
timeFrame: Day 0 through Week 60
measure: VRC07-523LS half-life (T1/2) following single dose administration
timeFrame: Day 0 through Week 48
measure: VRC07-523LS half-life (T1/2) following tow dose administration
timeFrame: Day 0 through Week 60
measure: Proportion of infants with PGT121.414.LS concentrations > 20 and > 50 mcg/mL following single/first dose administration
timeFrame: Week 12
measure: Proportion of infants with PGT121.414.LS concentrations > 20 and > 50 mcg/mL following two dose administration
timeFrame: Week 24
measure: Proportion of infants with VRC07-523LS concentrations > 10 and > 20 mcg/mL following single/first dose administration
timeFrame: Week 12
measure: Proportion of infants with PGT121.414.LS concentrations > 10 and > 20 mcg/mL following two dose administration
timeFrame: Week 24
measure: Proportion of infants with anti-PGT121.414.LS antibodies detected
timeFrame: Week 24
measure: Proportion of infants with anti-VRC07-523LS antibodies detected
timeFrame: Week 24
measure: Proportion of infants with anti-PGT121.414.LS antibodies detected
timeFrame: Week 48
measure: Proportion of infants with anti-VRC07-523LS antibodies detected
timeFrame: Week 48
measure: Proportion of infants with confirmed HIV infection following receipt of study product
timeFrame: Day 0 through Week 96
measure: 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
timeFrame: Day 0 through Week 13
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Site 5112, David Geffen School of Medicine at UCLA
state: California
city: Aurora
country: United States
facility: Site 5052, University of Colorado Denver
state: Colorado
city: Jacksonville
country: United States
facility: Site 5051, University of Florida Jacksonville
state: Florida
city: Miami
country: United States
facility: Site 5127, Pediatric Perinatal HIV
state: Florida
city: Atlanta
country: United States
facility: Site 5030, Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Site 5083, Rush University Cook County Hospital Chicago
state: Illinois
city: Baltimore
country: United States
facility: Site 5092, Johns Hopkins University Baltimore
state: Maryland
city: Bronx
country: United States
facility: Site 5114, Bronx-Lebanon Hospital Center
state: New York
city: Bronx
country: United States
facility: Site 5013, Jacobi Medical Center Bronx
state: New York
city: Memphis
country: United States
facility: Site 6501, St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Site 5128, Baylor College of Medicine/Texas Children's Hospital
state: Texas
city: Rio De Janeiro
country: Brazil
facility: Site 5072, Hospital Federal dos Servidores do Estado
city: Rio De Janeiro
country: Brazil
facility: Site 5097, Hospital Geral De Nova Iguacu Brazil
city: Kericho
country: Kenya
facility: Site 5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho
city: San Juan
country: Puerto Rico
facility: Site 5129, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research
city: Cape Town
country: South Africa
facility: Site 8950, FAMCRU
state: Parrow Valley
Study officials:
affiliation: University of California, Irvine
name: Coleen Cunningham
role: STUDY_CHAIR
References: