A Phase 1/2 Study of the Safety, Tolerability, and Pharmacokinetics of Cabotegravir in Neonates Exposed to HIV-1
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Maximum observed plasma concentration (Cmax) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of cabotegravir in neonates exposed to human immunodeficiency virus (HIV)-1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
盲法说明
Open-label study.
入排标准
- 年龄范围
- — 至 10 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •At least 37 weeks gestation at delivery.
- •<=10 days of life.
- •Birth weight at least 2 kg.
- •At Entry, neonate has initiated standard of care Antiretroviral drug (ARV) prophylaxis.
- •At Entry, neonate is generally healthy as determined by the site Investigator based on review of all available medical history information and physical examination findings.
- •Mother is on a Dolutegravir (DTG) based regimen for a minimum of 4 weeks prior to delivery, regardless of maternal viral load.
- •Mother is currently breastfeeding or plans to breastfeed infant.
- •Mother is of legal age or circumstance to provide independent informed consent and is willing and able to provide documented informed consent for her and her infant's participation in this study.
- •Mother has confirmed HIV-1 infection based on positive test results from 2 samples collected from 2 separate blood samples. Test results may be obtained from medical records or from testing performed during the study Screening period.
排除标准
- •Medical conditions
- •Severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by examining clinician.
- •Known maternal-fetal blood group incompatibility which can result in hemolytic disease of the newborn.
- •Known family history of G6PD deficiency.
- •Prior/Concomitant therapy
- •Mother who has previously received, is receiving, or will be receiving CAB post-partum.
- •Neonate or breastfeeding mother is receiving any disallowed medication.
- •Prior/Concurrent clinical study participation
- •Neonate has exposure to other investigational drugs that might interfere with study intervention metabolism.
- •Diagnostic assessments
- •Mother has known Integrase strand transfer inhibitor (InSTI) resistance.
- •At Entry, neonate with a confirmed, documented positive HIV Nucleic acid amplification test (NAAT) test result.
- •At Screening, neonate has any of the following laboratory test results:
- •Alanine transaminase or Aspartate aminotransferase of more than 2.5 x Upper limit of normal (ULN).
- •Total bilirubin in range for phototherapy at Entry.
- •Hemoglobin <13.0 g/dL.
- •Decreased white blood cells Grade 3 or above.
- •Platelets <50 000 cells/mm3
- •Creatinine value more than 1.3 the ULN for postnatal age as defined in Division of AIDS (DAIDS)
- •Albumin Grade 3 or higher.
- •Direct bilirubin Grade 3 and above.
- •Any other Grade ≥3 event on DAIDS toxicity table
- •Neonates with prior exchange transfusion. Other exclusion criteria
- •Mother or neonate has a condition that, in the site Investigator or designee's opinion, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
- •Neonate is receiving DTG as part of HIV prophylactic regimen. Liver safety exclusion criteria
- •Known maternal hepatitis B infection. Cardiac safety exclusion criteria
- •At screening, QT interval corrected using Fridericia's formula >450 msec.
研究组 & 干预措施
Stage 1: Single Oral Dose CAB (Cohort 1) group
Participants receive a single dose of oral CAB suspension on study Day 1.
干预措施: Oral CAB (Drug)
Stage 1: Multiple Oral Dose CAB (Cohort 2) group
Participants receive repeat doses of oral CAB suspension starting on study Day 1. Dose and dosing frequency to be determined based on data from Cohort 1.
干预措施: Oral CAB (Drug)
Stage 2: Single IM Dose CAB LA (Cohort 3) group
Participants receive a single IM dose of CAB LA on study Day 1. Dose to be determined based on data from Cohort 2.
干预措施: IM CAB LA (Drug)
Stage 2: Multiple IM Dose CAB LA (Cohort 4) group
Participants receive repeat IM doses of CAB LA starting on study Day 1. Dose and dosing frequency to be determined based on data from Cohort 3.
干预措施: IM CAB LA (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group
时间窗: At study Days 1, 3, 8, 15 and 22
Blood samples are collected at specific time points for PK analysis to determine Cmax.
Maximum observed plasma concentration (Cmax) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group
时间窗: At study Days 1, 3, 9,16, 28 and 42
Blood samples are collected at specific time points for PK analysis to determine Cmax.
Last observed plasma concentration (Clast) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group
时间窗: At study Days 1, 3, 8, 15 and 22
Blood samples are collected at specific time points for PK analysis to determine Clast.
Last observed plasma concentration (Clast) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group
时间窗: At study Days 1, 3, 9, 16, 28 and 42
Blood samples are collected at specific time points for PK analysis to determine Clast.
Area under the curve time 0 to the last time point (AUC0-t) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group
时间窗: At study Days 1, 3, 8, 15 and 22
Blood samples are collected at specific time points for PK analysis to determine AUC0-t.
Area under the curve time 0 to the last time point (AUC0-t) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group
时间窗: At study Days 1, 3, 9, 16, 28 and 42
Blood samples are collected at specific time points for PK analysis to determine AUC0-t.
Pre-dose concentrations (C0h) of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group
时间窗: At Study Days 1, 3, 7, 14, 28, 35, 42 and 49
Blood samples are collected at specific time points for PK analysis to determine C0h.
Pre-dose concentrations (C0h) of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group
时间窗: At Study Days 1, 3, 7, 21, 28, 42, 56, 70, 84, 98, 112, 140 and 168
Blood samples are collected at specific time points for PK analysis to determine C0h.
Post-dose concentrations of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group
时间窗: At Study Days 1, 3, 7, 14, 21, 28, 35, 42 and 49
Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations.
Post-dose concentrations of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group
时间窗: At Study Days 1, 3, 7, 14, 21, 28, 35, 42, 56, 70, 84, 98, 112, 140 and 168
Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations.
Number of participants with drug-related adverse event (AEs) by severity
时间窗: From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
A drug-related AE is any untoward medical occurrence in a clinical study participant considered related to the study intervention. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.
Number of participants with serious AEs (SAEs) by severity
时间窗: From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
An SAE is defined as any untoward medical occurrence that is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in death. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.
Number of participants with injection site reactions (ISRs) by severity
时间窗: From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
An ISR is defined as an adverse event which is localized at the injection site, typically includes pain, tenderness, erythema, redness, induration, swelling, nodules or pruritus, but may also encompass other reactions. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.
Number of participants who discontinue the study intervention due to AEs or injection intolerability
时间窗: From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
次要结局
- Number of participants developing Grade 3 and higher AEs and SAEs, by severity(From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group))
- Number of participants with Grade 3 and above bilirubin elevation.(From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group))