A Study to Investigate Cabotegravir for Neonates Exposed to HIV-1

Официальное название

A Phase 1/2 Study of the Safety, Tolerability, and Pharmacokinetics of Cabotegravir in Neonates Exposed to HIV-1

Обзор

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.

Вмешательства

• Препарат Oral CAB
  CAB administered once orally on study Day 1 to the Stage 1: Single Oral Dose CAB (Cohort 1) and multiple times to the Stage 1: Multiple Oral Dose CAB (Cohort 2) group. Dose and dosing frequency for Cohort 2 to be determined based on emerging data from Cohort 1.
• Препарат IM CAB LA
  CAB LA administered once intramuscularly on study Day 1 to the Stage 2: Single IM Dose CAB LA (Cohort 3) group and multiple times to the Stage 2: Multiple IM Dose CAB LA (Cohort 4) group, into the in the anterolateral thigh muscle of participants. Dose for Cohort 3 to be determined based on emerging data from Cohort 2. Dose and dosing frequency for Cohort 4 to be determined based on emerging data from Cohort 3.

Первичные конечные точки

• Maximum observed plasma concentration (Cmax) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group [Срок оценки: At study Days 1, 3, 8, 15 and 22]
• Maximum observed plasma concentration (Cmax) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group [Срок оценки: At study Days 1, 3, 9,16, 28 and 42]
• Last observed plasma concentration (Clast) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group [Срок оценки: At study Days 1, 3, 8, 15 and 22]
• Last observed plasma concentration (Clast) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group [Срок оценки: At study Days 1, 3, 9, 16, 28 and 42]
• 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 [Срок оценки: At study Days 1, 3, 8, 15 and 22]
• 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 [Срок оценки: At study Days 1, 3, 9, 16, 28 and 42]
• Pre-dose concentrations (C0h) of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group [Срок оценки: At Study Days 1, 3, 7, 14, 28, 35, 42 and 49]
• Pre-dose concentrations (C0h) of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group [Срок оценки: At Study Days 1, 3, 7, 21, 28, 42, 56, 70, 84, 98, 112, 140 and 168]
• Post-dose concentrations of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group [Срок оценки: At Study Days 1, 3, 7, 14, 21, 28, 35, 42 and 49]
• Post-dose concentrations of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group [Срок оценки: At Study Days 1, 3, 7, 14, 21, 28, 35, 42, 56, 70, 84, 98, 112, 140 and 168]

Вторичные конечные точки (2)

• Number of participants developing Grade 3 and higher AEs and SAEs, by severity [Срок оценки: 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. [Срок оценки: 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)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

ЮАР · 1 центр

• GSK Investigational Site — Parow Valley

Идентификаторы

NCT: NCT07275606 · 223560

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗