Pharmacokinetics and Safety of DolutegravIr in Neonate

NCT ID: NCT05590325

Last Updated: 2023-12-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-12
• Study Completion Date: 2024-12-31

Brief Summary

A Phase I/II, open-label, single arm, two-stage trial to evaluate the single and multi-dose PK and safety of DTG in HIV-exposed neonates on ARV prophylaxis. HIV-exposed term neonates born mothers with HIV on DTG-based antiretroviral therapy with a birth weight ≥2000 g who are on ARV postnatal prophylaxis will be enrolled.

Detailed Description

A Phase I/II, open-label, single arm, two-stage trial to evaluate the single and multi-dose PK and safety of DTG in HIV-exposed neonates on ARV prophylaxis. HIV-exposed term neonates born mothers with HIV on DTG-based antiretroviral therapy with a birth weight ≥2000 g who are on ARV postnatal prophylaxis will be enrolled.

Enrolment will be in two stages:

• Stage 1 will assess a single 5 mg dose of the DTG-DT in two sequential cohorts: Cohort 1A (n=8) and Cohort 1B (n=8).
• Stage 2 will assess multiple 5 mg doses of the DTG-DT and DTG-ODF in two parallel cohorts: Cohort 2A (n=20) and Cohort 2B (n=20).

Per national guidelines, all infants receive a birth HIV nucleic acid test (NAT). HIV NAT test results for the infant may or may not be available (HIV pending) at the time of study entry. HIV NAT results are typically available within 72 hours of the blood sample being taken and are checked and acted upon by the hospital HIV PMTCT service, as part of standard of care. If an HIV NAT result comes back positive whilst the neonate is on study, the neonate will not receive any further DTG doses, revert to standard of care antiretroviral therapy (ART), and be followed for safety for the duration of the study.

Primary Objectives:

• To evaluate the pharmacokinetics of dolutegravir (DTG) during the first 28 days of life in HIV-exposed term neonates (born to a mother with HIV) following administration of DTG dispersible tablet (DTG-DT) and DTG oral dispersible film (DTG-ODF)
• To determine the safety of DTG during the first 28 days of life in HIV-exposed term neonates following administration of DTG-DT and DTG-ODF

Secondary Objectives:

• To quantitatively and qualitatively assess the acceptability of DTG-DT and DTG-ODF for the neonate, the caregiver and health workers

Primary endpoints:

• DTG plasma pharmacokinetics parameters: area under the concentration time curve (AUC); maximum plasma concentration (Cmax), apparent clearance (CL/F), and trough concentration (Ctrough)
• Occurrence of the following events: adverse events of Grade 3 or higher; treatment-related adverse events of Grade 3 or higher; any adverse events

Secondary endpoints:

• Acceptability to caregivers and neonates of using DTG-DT will be measured by means of a questionnaire

Conditions

Hiv

Keywords

HIV exposed; Neonates

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

single arm, two-stage

Participants will be enrolled in two stages:

• Stage 1 will assess a single dose of the DTG-DT in two sequential cohorts: Cohort 1A (n=8) and Cohort 1B (n=8).
• Stage 2 will assess multiple-doses of the DTG-DT and the DTG-ODF in a single cohort: Cohort 2A (n=20) DTG-DT and Cohort 2B (n=20) DTG-ODF

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

Single dose of the DTG-DT in two sequential cohorts and multiple-doses of the DTG-DT or DTG-ODF in a two cohorts.

Qualitative Acceptability will be collected from mothers and health workers in structured discussion guides.

Interventions

Dolutegravir

Single dose of the DTG-DT in two sequential cohorts and multiple-doses of the DTG-DT or DTG-ODF in a two cohorts.

Qualitative Acceptability will be collected from mothers and health workers in structured discussion guides.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HIV-exposed neonate (pending HIV status) born to a woman within HIV on DTG-based ART
• Birth weight of ≥2000 g and on standard of care ARV prophylaxis

Cohort 1A: Infant <14 days of life Cohort 1B: Infant ≤3 days of life

• Low risk* HIV-exposed neonate (pending HIV status) born to a virologically suppressed woman on DTG-based ART

*Neonate born to a woman with a documented plasma HIV-1 RNA result <50 copies/mL in the 4 weeks prior to delivery or between delivery and infant study entry

• Birth weight of ≥2000 g and on standard of care ARV prophylaxis

Cohort 2: Infant <7 days of life

Exclusion Criteria

• • Less than 37 weeks gestational age at birth

• Known blood group incompatibilities which can result in hemolytic disease of the newborn (e.g., Rh-negative mother, presence of antibodies on neonatal red blood cells, etc.)
• Total bilirubin values approaching an exchange transfusion as defined by local guidelines (Section 18.2)
• Haemoglobin value of <13.0 g/dL
• Platelet count of less than 50,000 cells/mm3)
• Decreased total white blood cell count (Grade 3 and above)
• Creatinine value more than 1.3 the upper limit of normal (ULN) for gestational age and postnatal age (Grade 2 and above)
• AST or ALT of more than 2.5 the ULN (Grade 2 and above)
• Any other current Grade ≥3 event on the DAIDS toxicity table
• Severe congenital abnormalities or critically ill neonates at discretion of the examining clinician
• Receiving medicine(s) that can impact DTG pharmacokinetics (Section 8.7)
• Participation in another clinical trial
• HIV-infected neonates

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chiang Mai University

OTHER

Sponsor Role: collaborator

UNITAID

OTHER

Sponsor Role: collaborator

University of Stellenbosch

OTHER

Sponsor Role: collaborator

Desmond Tutu TB Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adrie Bekker, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Stellenbosch

Locations

Tygerberg Hospital

Cape Town, Western Cape, South Africa

Site Status: RECRUITING

Countries

South Africa

Central Contacts

Adrie Bekker, Prof

Role: CONTACT

Phone: +27 (0)219389198

Email: adrie@sun.ac.za

Tina Sachs, MSc

Role: CONTACT

Phone: +27 (0)620474701

Email: tsachs@sun.ca.za

Facility Contacts

Adrie Beker, Prof

Role: primary

References

Bekker A, Salvadori N, Rabie H, du Toit S, Than-In-At K, Groenewald M, Barnabas S, Ganger L, Luangcharoenkul T, Pingkarawat S, Capparelli EV, Owen A, Cressey R, Fry S, Le Roux G, Tawon Y, Kaewmalee J, Phitak T, Lallemant M, Cotton MF, Cressey TR. Safety and pharmacokinetics of dolutegravir dispersible tablets and oral films in term neonates exposed to HIV in South Africa (PETITE-DTG study): an open-label, randomised, phase 1/2 trial. Lancet HIV. 2025 Oct 8:S2352-3018(25)00239-5. doi: 10.1016/S2352-3018(25)00239-5. Online ahead of print.

Reference Type: DERIVED

PMID: 41075812 (View on PubMed)

Cressey TR, Salvadori N, Rabie H, du Toit S, Than-In-At K, Groenewald M, Capparelli E, Owen A, Cressey R, Lallemant M, Cotton MF, Bekker A. Single Doses of Pediatric Dolutegravir Dispersible Tablets in Neonates Support Multidosing: PETITE-Dolutegravir Study. J Acquir Immune Defic Syndr. 2025 Jun 1;99(2):195-201. doi: 10.1097/QAI.0000000000003652.

Reference Type: DERIVED

PMID: 39972540 (View on PubMed)

Other Identifiers

2019-36-SUN-MDR

Identifier Type: -

Identifier Source: org_study_id