Clinical Trials

MainTitle

Evaluating the Safety and Pharmacokinetics of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection

This study has been completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT02778204

First received: May 13, 2016
Last updated: December 4, 2019
Last Verified: December 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : Maraviroc
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Any life threatening adverse event, including death, assessed as at least possibly related to the study drug [ Time Frame: Measured through 7 Day Post Dose Visit for Cohort 1 ]
    Also includes AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by the Core Protocol Team to be at least possibly related to study drug
  • Any life threatening adverse event, including death, assessed as at least possibly related to the study drug [ Time Frame: Measured through Week 6 visit for Cohort 2 ]
    Also includes AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by the Core Protocol Team to be at least possibly related to study drug
  • Any life threatening AE, including death, assessed as at least possibly related to the study drug [ Time Frame: Measured through Week 6 ]
    Also includes AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by the Core Protocol Team to be at least possibly related to study drug
  • Failure to meet PK target of Cavg greater than or equal to 75 ng/mL [ Time Frame: Measured through Week 6 ]
    Cavg represents the area under the curve (AUC) divided by the duration of the dosing interval used to determine AUC.
Secondary Outcome Measures:
  • Any life threatening AE, including death, assessed as at least possibly related to the study drug [ Time Frame: Measured through Week 16 ]
    Also includes AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by the Core Protocol Team to be at least possibly related to the study drug

Enrollment: 47
Study Start Date: May 1, 2017
Study Completion Date: November 20, 2019
Primary Completion Date: September 6, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Cohort 1
Infants in both stratum of this cohort will receive a single dose of maraviroc solution within 3 days of birth and at Week 1 of life.
Drug: Maraviroc
  • For Cohort 1: 8 mg/kg oral solution as a single dose.
  • For Cohort 2: 8 mg/kg oral solution given twice daily.

Experimental: Cohort 2
Infants in both stratum of this cohort will receive maraviroc solution twice daily starting within 3 days of birth and continuing for up to 42 days.
Drug: Maraviroc
  • For Cohort 1: 8 mg/kg oral solution as a single dose.
  • For Cohort 2: 8 mg/kg oral solution given twice daily.

Detailed Description:

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 twice daily starting within 3 days of birth and continuing for up to 42 days. Based on evaluation of the Cohort 1 data, the initial daily dose of maraviroc oral solution to be administered in Cohort 2 will be 8 mg/kg dose given twice daily. 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.

Eligibility

Eligibility

Ages Eligible for Study: Child, Adult, Senior  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • 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).


Exclusion Criteria:
  • 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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02778204

Locations

United States, California
Usc La Nichd Crs
Los Angeles, California, United States, 90089
United States, Colorado
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States, 80045
United States, Illinois
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States, 60612
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, United States, 60614-3393
United States, Tennessee
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, United States, 38105-3678
Kenya
Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS
Kericho, Kenya, 20200
South Africa
Soweto IMPAACT CRS
Johannesburg, Gauteng, South Africa, 1862
Umlazi CRS
Durban, Kwa Zulu Natal, South Africa, 4001
Thailand
Siriraj Hospital ,Mahidol University NICHD CRS
Bangkok, Bangkoknoi, Thailand, 10700
Uganda
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
Kampala, Uganda

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Mark Mirochnick, MD Boston University School of Medicine/Boston Medical Center
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT02778204   History of Changes  
Other Study ID Numbers: IMPAACT 2007  
  20734  
Study First Received: May 13, 2016  
Last Updated: December 4, 2019  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
Infection
Communicable Diseases
Maraviroc

ClinicalTrials.gov processed this data on March 27, 2020
This information is provided by ClinicalTrials.gov.