Clinical trial NCT05406583: A Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1
Official title: A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Keywords: Antiretroviral
Dolutegravir
Newborn
Infant
HIV/AIDS
Perinatal
Pharmacokinetics
Prophylaxis
Prevention
Safety
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: ViiV Healthcare
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Mental Health (NIMH)
First posted: 2022-06-06
Enrollment: 48
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This study will test an anti-HIV drug (ARV) for newborn babies. The study will include a minimum of 36 and up to 108 mothers living with HIV and their newborn babies from Brazil, South Africa, Thailand, and the United States. Infants will be in the study for approximately 16 weeks (four months) after they are born. Mothers will not receive study drug and will exit the study after the Entry visit.


Eligibility criteria: Inclusion Criteria:

1. Mother is of legal age or circumstance to provide independent informed consent and is willing and able to provide written informed consent for her and permission for her infant's participation in this study.
2. Mother has confirmed HIV-1 infection based on positive test results from two samples collected from two separate blood collection tubes per Sample #1 and Sample #2 protocol requirements. Test results may be obtained from medical records or from testing performed during the study screening period:

   * For results obtained from medical records, adequate source documentation, including the date of specimen collection, date of testing or date of test result, name of test/assay performed, and test result, must be available in study records prior to study entry. Requirements related to laboratory operations (e.g., CLIA, GCLP, or VQA) and related to regulatory authority (e.g., FDA) approvals do not apply to results obtained from medical records.
   * If adequate source documentation is not available, Sample #1 and/or Sample #2 should be collected during the study screening period and tested in the site's designated testing laboratory. If both samples are tested using antibody tests, at least one of the samples must be tested in a laboratory that operates according to CLIA or equivalent (for US sites) or GCLP (for non-US sites) guidelines and participates in an appropriate external quality assurance program. If nucleic acid testing is used, at least one test must be performed in the site's CLIA-certified or equivalent (for US sites) or VQA-certified (for non-US sites) laboratory.
   * All study-specific samples tested to determine HIV-1 status must be whole blood, serum, or plasma. HIV testing methods and algorithms must be approved for each site by the IMPAACT Laboratory Center (for NIAID-funded sites) or Westat (for NICHD-funded sites). All test methods should be FDA-approved, if available.
3. At entry, infant meets DTG exposure requirements, based on mother's report and confirmed by medical records if available, as follows:

   * For Cohort 1, Strata 1A and 1C, and Cohort 2, Stratum 2A: Infant born to a mother who did not receive DTG during the two weeks immediately prior to delivery.
   * For Cohort 1, Stratum 1B, and Cohort 2, Stratum 2B: Infant born to a mother who received at least one dose of DTG less than or equal to 72 hours prior to delivery.
4. Infant was singleton with a gestational age at birth of at least 37 weeks.
5. At birth, infant's weight was as follows:

   * For Cohort 1, Strata 1A and 1B, and Cohort 2, Strata 2A and 2B: At least 2 kg
   * For Cohort 1, Stratum 1C:

     1. At least 2 kg
     2. At least 3 kg
6. At screening, infant has the following laboratory test results

   * ALT (normal)
   * AST (normal or Grade 1)
   * Total bilirubin (normal or Grade 1)
   * Hemoglobin (normal, Grade 1, or Grade 2)
   * White blood cells (normal, Grade 1, or Grade 2)
   * Platelets (normal, Grade 1, or Grade 2)
   * Creatinine (normal, Grade 1, or Grade 2)
7. At entry, infant is less than or equal to five days of life.
8. At entry, infant has initiated standard of care ARV prophylaxis (i.e., received at least one dose of ARV regimen prior to entry).
9. At entry, infant is generally healthy as determined by the site investigator based on review of all available medical history information and physical examination findings.

Exclusion Criteria:

1. Known maternal-fetal blood group incompatibility as evidenced by the presence of an unexpected clinically significant maternal red blood cell antibody that is known to cause hemolytic disease of the fetus and newborn.
2. Infant or breastfeeding mother is receiving any disallowed medication.
3. At entry, infant with a documented positive HIV nucleic acid test result.
4. Infants with prior exchange transfusion or with elevated bilirubin that would require exchange transfusion.
5. Mother or infant has any 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.

Primary outcomes:
measure: Proportion of infants classified as "study drug-related" safety failures.
timeFrame: Initial study drug dosing through 2 weeks after off treatment date
measure: Proportion of infants classified as safety failures.
timeFrame: Initial study drug dosing through 2 weeks after off treatment date
measure: Proportion of infants who are not able to tolerate the study drug.
timeFrame: Initial study drug dosing through study drug discontinuation
measure: C(last) for DTG
timeFrame: 28 months
measure: Area under the curve (AUC) for DTG
timeFrame: 28 months
measure: C(trough) for DTG
timeFrame: 28 months
measure: AUC(0-tau) for DTG
timeFrame: 28 months
Secondary outcomes:
measure: Proportion of infants classified as "study drug-related" safety failures.
timeFrame: Initial study drug dosing through Week 16
measure: Proportion of infants classified as safety failures.
timeFrame: Initial study drug dosing through Week 16
Other outcomes:
measure: Association of UGT1A1 gene sequence variants with DTG CL/F
timeFrame: 28 months
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA NICHD CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Denver NICHD CRS
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine NICHD CRS
state: Georgia
city: Chicago
country: United States
facility: Rush University, Cook County Hospital NICHD CRS
state: Illinois
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital Center NICHD CRS
state: New York
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine/ Texas Children's Hospital NICHD CRS
state: Texas
city: Johannesburg
country: South Africa
facility: Soweto
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits RHI Shandukani Research Centre CRS
state: Gauteng
city: Durban
country: South Africa
facility: Umlazi
state: Kwa Zulu Natal
city: Cape Town
country: South Africa
facility: FAMCRU
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University NICHD CRS
city: Chiang Mai
country: Thailand
facility: Chiang Mai University HIV Treatment
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital NICHD CRS
Study officials:
affiliation: BMC/Dept. of Pharmacy
name: Diana Clarke, Pharm.D.
role: STUDY_CHAIR
References: