A Study to Investigate Cabotegravir for Neonates Exposed to HIV-1

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.

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.