A Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1

HIV Clinical Trial

Official title:

A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05406583
• Other study ID #: IMPAACT 2023
• Secondary ID: 38637
• Status: Recruiting
• Phase: Phase 1
• Start date: October 5, 2022
• Est. completion date: February 28, 2025

Study information

• Verified date: April 2023
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: Sarah Bradford, MPH
• Phone: 1-919-321-3673
• Email: SBradford[@]fhi360.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: February 28, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Dolutegravir 0.5 mg/kg oral suspension
DTG 0.5 mg/kg liquid suspension administered orally
• Dolutegravir 5 mg Dispersible Tablets
DTG 5 mg DT administered orally

Locations

Country	Name	City	State
Brazil	University of Sao Paulo Brazil NICHD CRS	Ribeirão Preto	São Paulo
Puerto Rico	IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS	San Juan
Puerto Rico	University of Puerto Rico Pediatric HIV/AIDS Research CRS	San Juan
South Africa	FAMCRU	Cape Town
South Africa	Umlazi	Durban	Kwa Zulu Natal
South Africa	Soweto	Johannesburg	Gauteng
South Africa	Wits RHI Shandukani Research Centre	Johannesburg	Gauteng
Thailand	Siriraj Hospital, Mahidol University NICHD CRS	Bangkok
Thailand	Chiang Mai University HIV Treatment	Chiang Mai
Thailand	Chiangrai Prachanukroh Hospital NICHD CRS	Chiang Rai
United States	Emory University School of Medicine NICHD CRS	Atlanta	Georgia
United States	University of Colorado Denver NICHD CRS	Aurora	Colorado
United States	Bronx-Lebanon Hospital Center NICHD CRS	Bronx	New York
United States	Rush University, Cook County Hospital NICHD CRS	Chicago	Illinois
United States	Baylor College of Medicine/ Texas Children's Hospital NICHD CRS	Houston	Texas
United States	David Geffen School of Medicine at UCLA NICHD CRS	Los Angeles	California
United States	University of Southern California NICHD CRS	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (4)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH), ViiV Healthcare

Countries where clinical trial is conducted

United States,  Brazil,  Puerto Rico,  South Africa,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Association of UGT1A1 gene sequence variants with DTG CL/F		28 months
Primary	Proportion of infants classified as "study drug-related" safety failures.	An infant is classified as a "study drug-related" safety failure for the primary safety study objective if any of the following occurred after the initial study drug dosing through two weeks after permanent discontinuation of the study drug (i.e., two weeks after off treatment date): Grade 3 or 4 AE assessed as related to study drug, or; Death (Grade 5 AE) assessed as related to the study drug, or; Life-threatening AE assessed as related to study drug, or; AE assessed as related to study drug that leads to premature permanent discontinuation of the study drug.	Initial study drug dosing through 2 weeks after off treatment date
Primary	Proportion of infants classified as safety failures.	An infant is classified as a safety failure for the primary safety study objective if any of the following occurred after the initial study drug dosing through two weeks after permanent discontinuation of the study drug (i.e., two weeks after off treatment date): Grade 3 or 4 AE, or; Death (Grade 5 AE)	Initial study drug dosing through 2 weeks after off treatment date
Primary	Proportion of infants who are not able to tolerate the study drug.	An infant is considered not able to tolerate the study drug if the infant experiences problems taking the study drug or experiences any AE assessed as related to study drug that leads to premature permanent discontinuation of the study drug.	Initial study drug dosing through study drug discontinuation
Primary	C(last) for DTG		28 months
Primary	Area under the curve (AUC) for DTG		28 months
Primary	C(trough) for DTG		28 months
Primary	AUC(0-tau) for DTG		28 months
Secondary	Proportion of infants classified as "study drug-related" safety failures.	An infant is classified as a "study drug-related" safety failure for the secondary study safety objective if any of the following occurred after the initial study drug dosing through Week 16: Grade 3 or 4 AE assessed as related to study drug, or; Death (Grade 5 AE) assessed as related to the study drug, or; Life-threatening AE assessed as related to study drug, or; AE assessed as related to study drug that leads to premature permanent discontinuation of the study drug.	Initial study drug dosing through Week 16
Secondary	Proportion of infants classified as safety failures.	An infant is classified as a safety failure for the secondary study safety objective if any of the following occurred after the initial study drug dosing through Week 16: Grade 3 or 4 AE, or; Death (Grade 5 AE)	Initial study drug dosing through Week 16