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CompletedNCT02778204Updated Jan 4, 2022Results posted

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

A Phase 1 interventional study of Maraviroc and Maraviroc in HIV Infections, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 9 sites in 4 countries. Open to participants aged Up to 3 Days. Per ClinicalTrials.gov, last updated 2022-01-04.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention

Phase
Phase 1
Study type
Interventional
Enrollment
47
Allocation
Non-randomized
Ages
Up to 3 Days
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • HIV Infections

Keywords

  • Vertical HIV exposure
  • Neonates
  • Maraviroc
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 47 is below the median of 120 across 4,200 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.

Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 3 Days
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
47 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Maraviroc

  • Experimental
    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.

    Drug: Maraviroc

  • Experimental
    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.

    Drug: Maraviroc

  • Experimental
    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

    Drug: Maraviroc

Interventions

  • DrugMaraviroc

    8 mg/kg oral solution as a single dose.

  • DrugMaraviroc

    8 mg/kg oral solution given twice daily.

06

What researchers measure

Primary outcomes

  1. Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding

    Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

    Time frame: Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).

  2. Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis

    Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

    Time frame: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)

  3. Number of Participants Failing to Meet PK Target

    Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg \<75 ng/mL at each intensive PK visit. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

    Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

  4. Pharmacokinetic (PK) Parameter: Average Concentration (Cavg)

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

    Time frame: Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit

  5. Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC)

    Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours). For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

    Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

  6. Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)

    Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

    Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

  7. Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax)

    Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

    Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

  8. Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau)

    Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

    Time frame: Measured at Week 1 and Week 4 Visit

Secondary outcomes

  1. Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding

    Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

    Time frame: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)

  2. Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis

    Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

    Time frame: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)

07

Results

Posted Nov 23, 2020
Limitations and caveats
As with other Antiretrovirals (ARVs) in young infants, maraviroc PK parameters showed high intra- and inter-participant variability.

Participant flow

Accrual occurred between June 2017 and July 2019 in Kenya, Thailand, South Africa, and the United States at 9 different medical clinic sites. Pregnant mothers were screened and subsequently enrolled for 1 day at the same day their newborn infants were enrolled (within 3 days of life).

Participant flow — Overall Study
MilestoneCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
Started871616
Completed671212
Not completed2044
Withdrew: Adverse event1000
Withdrew: Withdrawal by subject0012
Withdrew: Lost to follow-up1021
Withdrew: Protocol violation0010
Withdrew: Eligibility violation0001

Outcome measures

PrimaryPercentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding

Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

Time frame:
Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).
Reported as:
Number · percentage of participants
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding
percentage of participantsCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding0 (0 to 45.9)0 (0 to 41.0)0 (0 to 26.5)0 (0 to 26.5)
PrimaryPercentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis

Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

Time frame:
Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)
Reported as:
Number · percentage of participants
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis
percentage of participantsCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis0 (0 to 36.9)0 (0 to 41.0)0 (0 to 20.6)0 (0 to 20.6)
PrimaryNumber of Participants Failing to Meet PK Target

Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg \<75 ng/mL at each intensive PK visit. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Time frame:
Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Reported as:
Number · participants
Number of Participants Failing to Meet PK Target
participantsCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
First Visit0034
Second Visit——45
PrimaryPharmacokinetic (PK) Parameter: Average Concentration (Cavg)

Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Time frame:
Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit
Reported as:
Median · ng/mL
Pharmacokinetic (PK) Parameter: Average Concentration (Cavg)
ng/mLCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
First Visit190.47 (93.54 to 1278.62)375.47 (110.40 to 684.84)152.24 (19.75 to 565.68)124.67 (17.07 to 550.86)
Second Visit——93.58 (32.92 to 488.21)101.39 (42.65 to 351.19)
PrimaryPharmacokinetic (PK) Parameter: Area-under-the-curve (AUC)

Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours). For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Time frame:
Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Reported as:
Median · ng*hr/mL
Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC)
ng*hr/mLCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
First Visit2285.68 (1122.53 to 15343.42)4506.17 (1325.02 to 8218.03)1826.87 (236.96 to 6788.18)1496.05 (204.89 to 6610.35)
Second Visit——1122.99 (395.01 to 5858.51)1216.62 (511.85 to 4214.34)
PrimaryPharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)

Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Time frame:
Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Reported as:
Median · ng/mL
Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)
ng/mLCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
First Visit227.3 (29.9 to 1618.4)550.5 (203.8 to 1153)256.9 (51.5 to 1468.4)308.8 (34.4 to 1273.5)
Second Visit128.9 (22.8 to 296.2)163.4 (8.7 to 609.4)416.5 (125.1 to 793.4)221.8 (76.5 to 738.7)
PrimaryPharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax)

Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Time frame:
Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Reported as:
Median · hours
Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax)
hoursCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
First Visit4.68 (1.05 to 12.75)1.52 (1.25 to 4.42)1.50 (0.83 to 4.00)3.00 (1.00 to 6.18)
Second Visit1.18 (1.05 to 1.25)1.08 (1.07 to 1.33)1.50 (1.00 to 4.00)2.19 (0.00 to 11.43)
PrimaryPharmacokinetic (PK) Parameter: Trough Concentration (Ctau)

Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Time frame:
Measured at Week 1 and Week 4 Visit
Reported as:
Median · ng/mL
Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau)
ng/mLCohort 2 Stratum 2ACohort 2 Stratum 2B
Week 1 Visit27.9 (0 to 138.9)23.4 (0 to 824.9)
Week 4 Visit34.4 (0 to 373.1)54.9 (8.2 to 233.9)
SecondaryPercentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding

Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

Time frame:
Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)
Reported as:
Number · percentage of participants
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding
percentage of participantsCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding0 (0 to 45.9)0 (0 to 41.0)0 (0 to 26.5)0 (0 to 26.5)
SecondaryPercentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis

Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, 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 Core Protocol Team to be at least possibly related to study drug

Time frame:
Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)
Reported as:
Number · percentage of participants
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis
percentage of participantsCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis0 (0 to 36.9)0 (0 to 41.0)0 (0 to 20.6)0 (0 to 20.6)

Adverse events

Collected over From study entry to study completion at Week 16 or premature study discontinuation. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1 Stratum 1A0/8 (0%)2/8 (25%)7/8 (87.5%)
Cohort 1 Stratum 1B0/7 (0%)1/7 (14.3%)7/7 (100%)
Cohort 2 Stratum 2A0/16 (0%)4/16 (25%)15/16 (93.8%)
Cohort 2 Stratum 2B0/16 (0%)2/16 (12.5%)14/16 (87.5%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
HypospadiasCongenital, familial and genetic disorders0/81/70/160/16
CyanosisCardiac disorders1/80/70/160/16
Staphylococcal sepsisInfections and infestations1/80/70/160/16
Slow response to stimuliNervous system disorders1/80/70/160/16
TremorNervous system disorders1/80/70/160/16
Haemolytic anaemiaBlood and lymphatic system disorders0/80/70/161/16
JaundiceHepatobiliary disorders0/80/70/161/16
Escherichia urinary tract infectionInfections and infestations0/80/70/161/16
Pneumonia bacterialInfections and infestations0/80/71/160/16
Sepsis neonatalInfections and infestations0/80/70/161/16
Most frequent other events
Showing 10 of 77
Most frequent other events
EventCohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2B
RashSkin and subcutaneous tissue disorders1/85/71/163/16
Haemoglobin decreasedInvestigations4/84/711/165/16
Blood bilirubin increasedInvestigations2/80/79/164/16
Neutrophil count decreasedInvestigations0/82/75/167/16
Nasal congestionRespiratory, thoracic and mediastinal disorders0/83/72/163/16
UnderweightMetabolism and nutrition disorders3/81/74/160/16
ImpetigoInfections and infestations0/82/70/160/16
Dermatitis diaperSkin and subcutaneous tissue disorders1/82/70/162/16
PapuleSkin and subcutaneous tissue disorders0/82/70/161/16
Rash neonatalSkin and subcutaneous tissue disorders0/82/71/163/16

Baseline characteristics

Includes all infants.

Age, Continuous
Age, Continuous(days)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
Mean (Standard Deviation)1.5 (1 to 2)0 (0 to 1)1 (0 to 2)2 (2 to 3)2 (1 to 2)
Age, Continuous
Age, Continuous(years)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
Median29.5 (29 to 37)26 (24 to 39)32 (26.5 to 36)32 (27.5 to 37.5)31 (26 to 37)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
Female547723
Male339924
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
Hispanic or Latino30205
Not Hispanic or Latino57141642
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
American Indian or Alaska Native00000
Asian00303
Native Hawaiian or Other Pacific Islander00000
Black or African American57101638
White30306
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(participants)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
United States7013020
South Africa1701422
Thailand00303
Kenya00022
Birth Weight
Birth Weight(kilograms)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
Median3.2 (2.8 to 3.5)3.4 (2.9 to 3.64)3.0 (2.9 to 3.19)3.0 (2.8 to 3.16)3.05 (2.9 to 3.4)
Birth Length
Birth Length(centimeters)Cohort 1 Stratum 1ACohort 1 Stratum 1BCohort 2 Stratum 2ACohort 2 Stratum 2BTotal
Median50.0 (49.0 to 51.25)50.0 (48.5 to 51.0)49.0 (49.0 to 50.5)48.5 (47.5 to 50.45)49.0 (48.0 to 51.0)

9 further baseline measures are reported on the registry.

08

Study locations

9 sites
  • Usc La Nichd Crs
    Los Angeles, California 90089, United States
  • Univ. of Colorado Denver NICHD CRS
    Aurora, Colorado 80045, United States
  • Rush Univ. Cook County Hosp. Chicago NICHD CRS
    Chicago, Illinois 60612, United States
  • Lurie Children's Hospital of Chicago (LCH) CRS
    Chicago, Illinois 60614-3393, United States
  • St. Jude Children's Research Hospital CRS
    Memphis, Tennessee 38105-3678, United States
  • Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS
    Kericho, 20200, Kenya
  • Soweto IMPAACT CRS
    Johannesburg, Gauteng 1862, South Africa
  • Umlazi CRS
    Durban, Kwa Zulu Natal 4001, South Africa
  • Siriraj Hospital ,Mahidol University NICHD CRS
    Bangkok, Bangkoknoi 10700, Thailand
09

References and documents

Study documents

  • Study protocol · Apr 13, 2016
  • Statistical analysis plan · Jun 11, 2018
  • Statistical analysis plan · Jan 24, 2020
  • Informed consent form · May 21, 2018

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 4, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02778204
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), ViiV Healthcare, GlaxoSmithKline
Responsible party
Sponsor
First posted
May 19, 2016
Start date
Jun 5, 2017
Primary completion
Sep 6, 2019
Completion
Nov 20, 2019
Results posted
Nov 23, 2020
Last update
Jan 4, 2022

Study contacts

Mark Mirochnick, MD
study chair · Boston University School of Medicine/Boston Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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