A Study to Investigate Cabotegravir for Neonates Exposed to HIV-1 (CABNATE)

A Phase 1/2 Study of the Safety, Tolerability, and Pharmacokinetics of Cabotegravir in Neonates Exposed to HIV-1

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of cabotegravir in neonates exposed to human immunodeficiency virus (HIV)-1.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Oral CAB; Drug: IM CAB LA

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• South Africa
  • Parow Valley, South Africa, 7505
    • Recruiting
    • GSK Investigational Site
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Principal Investigator: Adrie Bekker

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• At least 37 weeks gestation at delivery.
• <=10 days of life.
• Birth weight at least 2 kg.
• At Entry, neonate has initiated standard of care Antiretroviral drug (ARV) prophylaxis.
• At Entry, neonate is generally healthy as determined by the site Investigator based on review of all available medical history information and physical examination findings.
• Mother is on a Dolutegravir (DTG) based regimen for a minimum of 4 weeks prior to delivery, regardless of maternal viral load.
• Mother is currently breastfeeding or plans to breastfeed infant.
• Mother is of legal age or circumstance to provide independent informed consent and is willing and able to provide documented informed consent for her and her infant's participation in this study.
• Mother has confirmed HIV-1 infection based on positive test results from 2 samples collected from 2 separate blood samples. Test results may be obtained from medical records or from testing performed during the study Screening period.

Exclusion Criteria:

Medical conditions

• Severe congenital malformation or other medical condition not compatible with life or that would interfere with study participation or interpretation, as judged by examining clinician.
• Known maternal-fetal blood group incompatibility which can result in hemolytic disease of the newborn.
• Known family history of G6PD deficiency.
• Prior/Concomitant therapy
• Mother who has previously received, is receiving, or will be receiving CAB post-partum.
• Neonate or breastfeeding mother is receiving any disallowed medication.
• Prior/Concurrent clinical study participation
• Neonate has exposure to other investigational drugs that might interfere with study intervention metabolism.
• Diagnostic assessments
• Mother has known Integrase strand transfer inhibitor (InSTI) resistance.
• At Entry, neonate with a confirmed, documented positive HIV Nucleic acid amplification test (NAAT) test result.

• At Screening, neonate has any of the following laboratory test results:

  • Alanine transaminase or Aspartate aminotransferase of more than 2.5 x Upper limit of normal (ULN).
  • Total bilirubin in range for phototherapy at Entry.
  • Hemoglobin <13.0 g/dL.
  • Decreased white blood cells Grade 3 or above.
  • Platelets <50 000 cells/mm3
  • Creatinine value more than 1.3 the ULN for postnatal age as defined in Division of AIDS (DAIDS)
  • Albumin Grade 3 or higher.
  • Direct bilirubin Grade 3 and above.
• Any other Grade ≥3 event on DAIDS toxicity table
• Neonates with prior exchange transfusion. Other exclusion criteria
• Mother or neonate has a condition that, in the site Investigator or designee's opinion, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
• Neonate is receiving DTG as part of HIV prophylactic regimen. Liver safety exclusion criteria
• Known maternal hepatitis B infection. Cardiac safety exclusion criteria
• At screening, QT interval corrected using Fridericia's formula >450 msec.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: Single Oral Dose CAB (Cohort 1) group; Participants receive a single dose of oral CAB suspension on study Day 1.	Drug: Oral CAB; CAB administered once orally on study Day 1 to the Stage 1: Single Oral Dose CAB (Cohort 1) and multiple times to the Stage 1: Multiple Oral Dose CAB (Cohort 2) group. Dose and dosing frequency for Cohort 2 to be determined based on emerging data from Cohort 1.; Other Names: Cabotegravir
Experimental: Stage 1: Multiple Oral Dose CAB (Cohort 2) group; Participants receive repeat doses of oral CAB suspension starting on study Day 1. Dose and dosing frequency to be determined based on data from Cohort 1.	Drug: Oral CAB; CAB administered once orally on study Day 1 to the Stage 1: Single Oral Dose CAB (Cohort 1) and multiple times to the Stage 1: Multiple Oral Dose CAB (Cohort 2) group. Dose and dosing frequency for Cohort 2 to be determined based on emerging data from Cohort 1.; Other Names: Cabotegravir
Experimental: Stage 2: Single IM Dose CAB LA (Cohort 3) group; Participants receive a single IM dose of CAB LA on study Day 1. Dose to be determined based on data from Cohort 2.	Drug: IM CAB LA; CAB LA administered once intramuscularly on study Day 1 to the Stage 2: Single IM Dose CAB LA (Cohort 3) group and multiple times to the Stage 2: Multiple IM Dose CAB LA (Cohort 4) group, into the in the anterolateral thigh muscle of participants. Dose for Cohort 3 to be determined based on emerging data from Cohort 2. Dose and dosing frequency for Cohort 4 to be determined based on emerging data from Cohort 3.; Other Names: Cabotegravir long-acting
Experimental: Stage 2: Multiple IM Dose CAB LA (Cohort 4) group; Participants receive repeat IM doses of CAB LA starting on study Day 1. Dose and dosing frequency to be determined based on data from Cohort 3.	Drug: IM CAB LA; CAB LA administered once intramuscularly on study Day 1 to the Stage 2: Single IM Dose CAB LA (Cohort 3) group and multiple times to the Stage 2: Multiple IM Dose CAB LA (Cohort 4) group, into the in the anterolateral thigh muscle of participants. Dose for Cohort 3 to be determined based on emerging data from Cohort 2. Dose and dosing frequency for Cohort 4 to be determined based on emerging data from Cohort 3.; Other Names: Cabotegravir long-acting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group	Blood samples are collected at specific time points for PK analysis to determine Cmax.	At study Days 1, 3, 8, 15 and 22
Maximum observed plasma concentration (Cmax) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group	Blood samples are collected at specific time points for PK analysis to determine Cmax.	At study Days 1, 3, 9,16, 28 and 42
Last observed plasma concentration (Clast) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group	Blood samples are collected at specific time points for PK analysis to determine Clast.	At study Days 1, 3, 8, 15 and 22
Last observed plasma concentration (Clast) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group	Blood samples are collected at specific time points for PK analysis to determine Clast.	At study Days 1, 3, 9, 16, 28 and 42
Area under the curve time 0 to the last time point (AUC0-t) of CAB in participants from Stage 1: Single Oral Dose CAB (Cohort 1) group	Blood samples are collected at specific time points for PK analysis to determine AUC0-t.	At study Days 1, 3, 8, 15 and 22
Area under the curve time 0 to the last time point (AUC0-t) of CAB LA in participants from Stage 2: Single IM Dose CAB LA (Cohort 3) group	Blood samples are collected at specific time points for PK analysis to determine AUC0-t.	At study Days 1, 3, 9, 16, 28 and 42
Pre-dose concentrations (C0h) of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group	Blood samples are collected at specific time points for PK analysis to determine C0h.	At Study Days 1, 3, 7, 14, 28, 35, 42 and 49
Pre-dose concentrations (C0h) of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group	Blood samples are collected at specific time points for PK analysis to determine C0h.	At Study Days 1, 3, 7, 21, 28, 42, 56, 70, 84, 98, 112, 140 and 168
Post-dose concentrations of CAB in participants from Stage 1: Multiple Oral Dose CAB (Cohort 2) group	Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations.	At Study Days 1, 3, 7, 14, 21, 28, 35, 42 and 49
Post-dose concentrations of CAB LA in participants from Stage 2: Multiple IM Dose CAB LA (Cohort 4) group	Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations.	At Study Days 1, 3, 7, 14, 21, 28, 35, 42, 56, 70, 84, 98, 112, 140 and 168
Number of participants with drug-related adverse event (AEs) by severity	A drug-related AE is any untoward medical occurrence in a clinical study participant considered related to the study intervention. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.	From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
Number of participants with serious AEs (SAEs) by severity	An SAE is defined as any untoward medical occurrence that is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in death. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.	From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
Number of participants with injection site reactions (ISRs) by severity	An ISR is defined as an adverse event which is localized at the injection site, typically includes pain, tenderness, erythema, redness, induration, swelling, nodules or pruritus, but may also encompass other reactions. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.	From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
Number of participants who discontinue the study intervention due to AEs or injection intolerability	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.	From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants developing Grade 3 and higher AEs and SAEs, by severity	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in death. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.	From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)
Number of participants with Grade 3 and above bilirubin elevation.	The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.	From Day 1 up to 2-months post last dose administration (last dose administered at Day 1 to the single dose groups, at Month 1 to Stage 1: Multiple Oral Dose CAB (Cohort 2) group and at Month 6 to Stage 2: Multiple IM Dose CAB LA (Cohort 4) group)

Collaborators and Investigators

• Sponsor: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2026
• Primary Completion (Estimated): October 10, 2029
• Study Completion (Estimated): October 10, 2029

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Safety; HIV; Pharmacokinetics; Tolerability; Neonate; Cabotegravir
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; cabotegravir
• Other Study ID Numbers: 223560

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/documents/About_ViiV_Patient_Level_Data_Sharing_Final_25Sep2023.pdf.
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No