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

NCT ID: NCT02778204

Last Updated: 2022-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-05
• Study Completion Date: 2019-11-20

Brief Summary

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

Detailed Description

Maraviroc is a C-C Chemokine Receptor 5 (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 was to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in HIV-1-exposed infants at risk for mother-to-child HIV transmission. This study also aimed to determine an appropriate dose of maraviroc during the first six weeks of life.

The study allowed up to 72 mother-infant pairs in two cohorts to achieve a target of 36 evaluable infants receiving the final recommended dose of maraviroc. Because maraviroc interacts with the antiretroviral drug efavirenz (EFV) in adults, infants in this study were stratified within the cohorts based on their exposure to maternal EFV. Cohort 1 was stratified by in utero exposure to maternal EFV, with infants in both strata receiving a single dose of maraviroc solution within three days of birth and another single dose at Week 1 of life. Stratum 1A included infants without in utero exposure to maternal EFV during the eight weeks immediately before delivery. Stratum 1B included infants with in utero exposure to maternal EFV for a minimum of two weeks immediately before delivery.

Cohort 2 was stratified by exposure to maternal EFV after birth, with infants in both strata receiving maraviroc oral solution twice daily starting within three 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 was 8 mg/kg dose given twice daily. Stratum 2A included infants without any exposure to maternal EFV either in utero during the eight weeks immediately before delivery or while breastfeeding. Stratum 2B included 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 attended an entry visit within three days after the infant's birth. Participants attended five to six study visits through Week 16. Visits included medical history reviews, physical examinations, blood collection from the mother and/or infant, HIV testing, and adherence counseling.

Conditions

HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cohort 1 Stratum 1A

Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

8 mg/kg oral solution as a single dose.

Cohort 1 Stratum 1B

Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

8 mg/kg oral solution as a single dose.

Cohort 2 Stratum 2A

Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

8 mg/kg oral solution given twice daily.

Cohort 2 Stratum 2B

Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

8 mg/kg oral solution given twice daily.

Interventions

Maraviroc

8 mg/kg oral solution as a single dose.

Intervention Type: DRUG

Maraviroc

8 mg/kg oral solution given twice daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Mother was of legal age to provide independent informed consent for research participation and was willing and able to provide written informed consent for her and her infant's participation in this study.
• Mother had 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 met 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 were 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 were 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 was not receiving maternal EFV. Note: Breastfeeding and formula feeding infants were 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, intended to breastfeed for a minimum of six weeks and continued to receive maternal EFV while breastfeeding. Note: Only breastfeeding infants were 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 was less than or equal to 3 days old.
• At entry, infant had 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 had initiated antiretroviral prophylaxis that did not include a potent CYP3A4 inhibitor or inducer. See the protocol for more information.
• At entry, infant was 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 had 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 was receiving any disallowed medication listed in the protocol.
• Mother received maraviroc during pregnancy.

• Maximum Eligible Age: 3 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Mirochnick, MD

Role: STUDY_CHAIR

Boston University School of Medicine/Boston Medical Center

Locations

Usc La Nichd Crs

Los Angeles, California, United States

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, United States

Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, United States

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, United States

Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS

Kericho, , Kenya

Soweto IMPAACT CRS

Johannesburg, Gauteng, South Africa

Umlazi CRS

Durban, KwaZulu-Natal, South Africa

Siriraj Hospital ,Mahidol University NICHD CRS

Bangkok, Bangkoknoi, Thailand

Countries

United States; Kenya; South Africa; Thailand

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Primary Statistical Analysis Plan

View Document

Document Type: Statistical Analysis Plan: PK Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf

Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017

Other Identifiers

20734

Identifier Type: REGISTRY

Identifier Source: secondary_id

IMPAACT 2007

Identifier Type: -

Identifier Source: org_study_id