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

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ClinicalTrials.gov Identifier: NCT02778204
Recruitment Status : Recruiting
First Posted : May 19, 2016
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Maraviroc Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
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
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Maraviroc

Arm Intervention/treatment
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.





Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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 :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02778204


Locations
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United States, California
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program Recruiting
La Jolla, California, United States, 92093-0672
Contact: Megan Loughran, B.A.    858-534-9218    meloughran@ucsd.edu   
Usc La Nichd Crs Recruiting
Los Angeles, California, United States, 90089
Contact: Eva A. Operskalski, Ph.D.    323-865-1554    eva@usc.edu   
United States, Colorado
Univ. of Colorado Denver NICHD CRS Recruiting
Aurora, Colorado, United States, 80045
Contact: Emily Barr, C.P.N.P., C.N.M., M.S.N.    720-777-6752    emily.barr@childrenscolorado.org   
United States, Illinois
Rush Univ. Cook County Hosp. Chicago NICHD CRS Recruiting
Chicago, Illinois, United States, 60612
Contact: Maureen McNichols, R.N., M.S.N., C.C.R.C.    312-572-4541    maureen_mcnichols@rush.edu   
Lurie Children's Hospital of Chicago (LCH) CRS Recruiting
Chicago, Illinois, United States, 60614-3393
Contact: Margaret Ann Sanders, M.P.H.    312-227-8275    msanders@luriechildrens.org   
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS Withdrawn
Boston, Massachusetts, United States, 02118
United States, Tennessee
St. Jude Children's Research Hospital CRS Recruiting
Memphis, Tennessee, United States, 38105-3678
Contact: Jill Utech, M.S.N.    901-595-5059    jill.utech@stjude.org   
Kenya
Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS Recruiting
Kericho, Kenya, 20200
Contact: Samwel K. Chirchir, R.N., B.Sc.    254-522-030388    Samwel.Chirchir@usamru-k.org   
South Africa
Soweto IMPAACT CRS Recruiting
Johannesburg, Gauteng, South Africa, 1862
Contact: Nasreen Abrahams, M.B.A., B.Tech    27-11-9899700    abrahamsn@phru.co.za   
Umlazi CRS Recruiting
Durban, Kwa Zulu Natal, South Africa, 4001
Contact: Vani Chetty    27-31-2601998    Chettyv1@ukzn.ac.za   
Thailand
Siriraj Hospital ,Mahidol University NICHD CRS Recruiting
Bangkok, Bangkoknoi, Thailand, 10700
Contact: Watcharee Lermankul    66-2-4197000 ext 5695    watchareeped@gmail.com   
Uganda
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS Recruiting
Kampala, Uganda
Contact: Carolyne P. Onyango, MB ChB, M.S.    256-414-541044    carolonyango@mujhu.org   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Chair: Mark Mirochnick, MD Boston University School of Medicine/Boston Medical Center

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02778204     History of Changes
Other Study ID Numbers: IMPAACT 2007
20734 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: May 19, 2016    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Maraviroc
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
CCR5 Receptor Antagonists