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
概览
- 阶段
- 1 期
- 干预措施
- PGT121.414.LS
- 疾病 / 适应症
- HIV-1
- 发起方
- National Institute of Allergy and Infectious Diseases (NIAID)
- 入组人数
- 48
- 试验地点
- 17
- 主要终点
- VRC07-523LS area under the curve (AUC(0-12WK))
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Cohort 1 Stratum Formula Fed (FF)
Single subcutaneous (SC) dose of PGT121.414.LS at birth, based on weight.
干预措施: PGT121.414.LS
Cohort 1 Stratum Breastfed (BF)
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.
干预措施: PGT121.414.LS
Cohort 2 Stratum FF
Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight.
干预措施: PGT121.414.LS
Cohort 2 Stratum FF
Single SC doses of PGT121.414.LS and VRC07-523LS at birth, based on weight.
干预措施: VRC07-523LS
Cohort 2 Stratum BF
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.
干预措施: PGT121.414.LS
Cohort 2 Stratum BF
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.
干预措施: VRC07-523LS
结局指标
主要结局
VRC07-523LS area under the curve (AUC(0-12WK))
时间窗: Day 0 through Week 12
PGT121.414.LS concentration at the end of the first dose interval (C(12WK)) (single/first dose)
时间窗: Week 12
PGT121.414.LS maximum concentration (Cmax) (single/first dose)
时间窗: Day 0 through Week 48
VRC07-523LS time of maximum concentration (Tmax) (single/first dose)
时间窗: Day 0 through Week 48
VRC07-523LS concentration at the end of the first dose interval (C(12WK)) single/first dose)
时间窗: Week 12
Proportion of infants with at least one Grade 3 or higher AE assessed as related to study product (one dose)
时间窗: Day 0 through Week 12
Proportion of infants with at least one Grade 3 or higher AE (two doses)
时间窗: 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)
时间窗: Day 0 through Week 24
PGT121.414.LS area under the curve (AUC(0-12WK)) (single/first dose)
时间窗: Day 0 through Week 12
VRC07-523LS maximum concentration (Cmax) (single/first dose)
时间窗: Day 0 through Week 48
Proportion of infants with at least one Grade 3 or higher Adverse Event (AE) (one dose)
时间窗: Day 0 through Week 12
PGT121.414.LS time of maximum concentration (Tmax) (single/first dose)
时间窗: Day 0 through Week 48
PGT121.414.LS concentration at the end of the second dose interval (C(24WK)) (two doses)
时间窗: Week 24
VRC07-523LS concentration at the end of the second dose interval (C(24WK)) (two doses)
时间窗: Week 24
次要结局
- 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 at least one Grade 2 or higher AE (two doses)(Day 0 through Week 24)
- PGT121.414.LS half-life (T1/2) following two dose administration(Day 0 through Week 60)
- VRC07-523LS AUC(0-48WK) after single dose administration(Week 48)
- VRC07-523LS concentration after single dose administration(Week 48)
- VRC07-523LS half-life (T1/2) following single dose administration(Day 0 through Week 48)
- 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 any AEs that lead to study product discontinuation(Day 0 through Week 12)
- PGT121.414.LS concentration after single dose administration(Week 48)
- Proportion of infants with confirmed HIV infection following receipt of 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 anti-PGT121.414.LS antibodies detected(Week 48)
- Proportion of infants with anti-VRC07-523LS antibodies detected(Week 48)
- PGT121.414.LS AUC(0-48WK) after single dose administration(Week 48)
- PGT121.414.LS concentration after two dose administration(Week 60)
- VRC07-523LS concentration after two dose administration(Week 60)
- VRC07-523LS apparent clearance (CL/F)(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)
- 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)
- 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)
- VRC07-523LS half-life (T1/2) following tow dose administration(Day 0 through Week 60)
- 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)