Study Objectives

Primary Objectives

  1. Determine the steady-state AUC0-24h, Cmax, and C24h of ABC, DTG, and 3TC and confirm the dosing of ABC/DTG/3TC dispersible and immediate release tablets that achieves protocol-defined PK targets for ABC, DTG, and 3TC in children less than 12 years of age. 
  2. Evaluate the safety profile of 24 weeks of treatment with ABC/DTG/3TC dispersible tablets and ABC/DTG/3TC immediate release tablets among children less than 12 years of age. 

Secondary Objectives 

  1. Determine the PK of ABC, DTG, and 3TC, and clinical covariates that influence PK disposition, among children less than 12 years of age using population PK analysis of intensive and sparse PK samples collected over 48 weeks of treatment with ABC/DTG/3TC dispersible and immediate release tablets. 
  2. Evaluate the safety profile of 48 weeks, and additionally up to 144 weeks, of treatment with ABC/DTG/3TC dispersible tablets and ABC/DTG/3TC immediate release tablets among children less than 12 years of age. 
  3. Evaluate virologic and immunologic responses at 4, 24, and 48 weeks, and additionally up to 144 weeks, of treatment with ABC/DTG/3TC dispersible tablets and ABC/DTG/3TC immediate release tablets among children less than 12 years of age. 
  4. Evaluate changes in lipid profiles at 4, 24, and 48 weeks of treatment with ABC/DTG/3TC dispersible tablets and ABC/DTG/3TC immediate release tablets among children less than 12 years of age. 
  5. Evaluate adherence to and palatability and acceptability of ABC/DTG/3TC dispersible tablets and ABC/DTG/3TC immediate release tablets among children less than 12 years of age at 4, 24 and 48 weeks of treatment.
  6. Evaluate HIV-1 genotypes and phenotypes among children less than 12 years of age who experience virologic failure while receiving treatment with ABC/DTG/3TC dispersible tablets or ABC/DTG/3TC immediate release tablets. 

Study Design: A Phase I/II, multi-site, open-label, multiple dose, non-comparative study to assess the pharmacokinetics (PK), safety, and tolerability of fixed dose combination abacavir (ABC)/ dolutegravir (DTG)/ lamivudine (3TC) in HIV-1-infected children less than 12 years of age. The study will be conducted among at least 50 and up to 75 children. Children are expected to be enrolled at study sites in Botswana, South Africa, Thailand, and the US. 

At least 25 children will be less than six years of age and at least 25 will be six to less than 12 years of age. Children will be enrolled in weight bands and will receive study drug as shown in Table 1 below. Accrual into all weight bands will occur concurrently, and the age-based quotas will apply across weight bands. 

Study Population and Size: This study will be conducted among HIV-1-infected children less than 12 years of age across all the participating sites. Globally: At least 50 and up to 75 children in Botswana, South Africa, Thailand, and the USA. In Botswana: up to 18 participants (Gaborone and Molepolole).

Study Duration: Up to approximately 48 months total. Accrual is expected to require approximately 12 months; enrolled children will be followed for at least 48 and up to 144 weeks. The estimated date of study completion is January 31st 2023. 

Sponsor:

  • National Institute of Allergy and Infectious Diseases 
  • Eunice Kennedy Shriver 
  • National Institute of Child Health and Human Development 
  • National Institute of Mental Health