HIV-1
Conditions
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.
Interventions
DRUGPGT121.414.LS
Administered SC in the thigh
DRUGVRC07-523LS
Administered SC in the thigh
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
National Institute of Allergy and Infectious Diseases Vaccine Research Center (NIAID VRC)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 72 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PGT121.414.LS concentration at the end of the first dose interval (C(12WK)) (single/first dose) | Week 12 |
| 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 |
| VRC07-523LS maximum concentration (Cmax) (single/first dose) | Day 0 through Week 48 |
| 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 |
| 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 |
| PGT121.414.LS concentration at the end of the second dose interval (C(24WK)) (two doses) | Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| 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 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 |
| 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 |
Countries
Brazil, Kenya, Puerto Rico, South Africa, United States, Zimbabwe
Contacts
CONTACTEmily Brown
STUDY_CHAIRColeen Cunningham
University of California, Irvine
Outcome results
None listed