Summary

at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

This study will evaluate the safety, tolerability, and pharmacokinetics of maraviroc in infants at risk for mother-to-child HIV transmission and determine an appropriate dose of maraviroc during the first 6 weeks of life.

Official Title

Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection

Details

Maraviroc is a CCR5 receptor antagonist used to treat HIV infection in adults. Adding maraviroc to a standard of care prophylaxis regimen may also reduce the risk of perinatal transmission of HIV. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in HIV-1-exposed infants at risk for mother-to-child HIV transmission. This study will also determine an appropriate dose of maraviroc during the first 6 weeks of life.

The study will enroll up to 72 mother-infant pairs in two cohorts. Because maraviroc interacts with the antiretroviral drug efavirenz (EFV) in adults, infants in this study will be stratified within the cohorts based on their exposure to maternal EFV. Cohort 1 will be stratified by in utero exposure to maternal EFV, with infants in both strata receiving a single dose of maraviroc solution within 3 days of birth and another single dose at Week 1 of life. Stratum 1A includes infants without in utero exposure to maternal EFV during the 8 weeks immediately before delivery. Stratum 1B includes infants with in utero exposure to maternal EFV for a minimum of 2 weeks immediately before delivery.

Cohort 2 will be stratified by exposure to maternal EFV after birth, with infants in both strata receiving maraviroc oral solution once or twice daily starting within 3 days of birth and continuing for up to 42 days. The initial starting dose for Cohort 2 will be determined based on findings from Cohort 1. Stratum 2A includes infants without any exposure to maternal EFV either in utero during the 8 weeks immediately before delivery or while breastfeeding. Stratum 2B includes breastfeeding infants with exposure to maternal EFV both in utero and after birth while breastfeeding, for a minimum of 2 weeks immediately before delivery and while breastfeeding.

Participants will attend an entry visit within 3 days after the infant's birth. Participants will attend 5 to 6 study visits through Month 4. Visits may include medical history reviews, physical examinations, blood collection from the mother and/or infant, HIV testing, and adherence counseling.

Keywords

HIV Infections Infection Communicable Diseases Maraviroc

Eligibility

You can join if…

  • Mother is of legal age to provide independent informed consent for research participation and is willing and able to provide written informed consent for her and her infant's participation in this study.
  • Mother has confirmed HIV-1 infection based on testing of two samples collected at different time points. More information on this criterion can be found in the protocol.
  • At entry, infant meets EFV exposure requirements, based on mother's report and confirmed by medical records if available, as follows:
  • For Cohort 1, Stratum 1A: Infant born to a mother who did not receive EFV during the eight weeks immediately prior to delivery. Note: Breastfeeding and formula feeding infants are eligible for this stratum.
  • For Cohort 1, Stratum 1B: Infant born to a mother who received EFV for a minimum of two weeks immediately prior to delivery. Note: Breastfeeding and formula feeding infants are eligible for this stratum.
  • For Cohort 2, Stratum 2A: Infants born to a mother who did not receive EFV during the eight weeks immediately prior to delivery and if breastfeeding, mother is not receiving maternal EFV. Note: Breastfeeding and formula feeding infants are eligible for this stratum.
  • For Cohort 2, Stratum 2B: Breastfeeding infants born to a mother who received EFV for a minimum of two weeks immediately prior to delivery, intends to breastfeed for a minimum of six weeks and will continue to receive maternal EFV while breastfeeding. Note: Only breastfeeding infants are eligible for this stratum.
  • At birth, infant's estimated gestational age was at least 37 weeks. Note: If gestational age at birth is not documented in the infant's available birth records,study staff may assess gestational age at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
  • At birth, infant's weight was at least 2 kg. Note: If weight at birth is not documented in the infant's available birth records, study staff may assess infant weight at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
  • At entry, infant is less than or equal to 3 days old.
  • At entry, infant has the following lab values:
  • Grade 0 alanine transaminase (ALT) (normal)
  • Less than or equal to Grade 1 aspartate aminotransferase (AST) and total bilirubin
  • Less than or equal to Grade 2 hemoglobin, white blood cell counts, platelet counts
  • At entry, infant has initiated antiretroviral prophylaxis that does not include a potent CYP3A4 inhibitor or inducer. See the protocol for more information.
  • At entry, infant is assessed by the site investigator or designee as generally healthy based on review of available medical records, other available medical history information, and physical examination findings.
  • Born after singleton delivery (not after multiple birth).

You CAN'T join if...

  • Infant has any other 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; for example, severe congenital malformation, other medical condition, or clinically significant finding from physical examination.
  • At entry, any positive infant HIV nucleic acid test result (results are not required to be available prior to entry but any positive results obtained prior to entry are exclusionary).
  • At entry, infant or breastfeeding mother is receiving any disallowed medication listed in the protocol.
  • Mother received maraviroc during pregnancy.

Locations

  • University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program accepting new patients
    La Jolla, California, 92093-0672, United States
  • Usc La Nichd Crs accepting new patients
    Los Angeles, California, 90089, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT02778204
Phase
Phase 1
Study Type
Interventional
Last Updated
March 12, 2018