Study Objectives

Primary Objectives

  • To select a Dolutegravir dose for chronic dosing in infants, children and adolescents that achieves similar exposure to the Dolutegravir adult dose selected from the Phase IIb clinical trial in ART-naïve adult subjects.
  • To determine the safety and tolerability of Dolutegravir in HIV-1 infected infants, children and adolescents at 24 and 48 weeks.
  • To evaluate the steady-state pharmacokinetics of Dolutegravir in combination with other antiretrovirals (OBT) in treatment-experienced HIV-1 infected infants, children and adolescents and to determine the dose of Dolutegravir that achieves a targeted AUC24 (primary PK endpoint) and C24h (secondary PK endpoint) in this population.

Secondary Objectives

  • To evaluate the antiviral activity of Dolutegravir in combination with an OBT by measuring virologic response in infants, children and adolescents at 24 and 48 weeks.
  • To evaluate the effect on immunologic response from baseline to 24 and 48 weeks.
  • To assess changes in HIV-1 genotype and phenotype to Dolutegravir and other components of the OBT in subjects experiencing virologic failure.
  • To determine Dolutegravir exposure, its variability and clinical covariates that impact Dolutegravir disposition (e.g. age, weight) using intensive and sparse sampling and population pharmacokinetic analysis.
  • To determine the extended long term (≥48 weeks) safety and tolerability of Dolutegravir in HIV-1 infected infants, children and adolescents.
  • To explore the relationship between Dolutegravir exposure and the antiviral activity

Study Design: P1093 is a Phase I/II multi-center, open-label non-comparative study of approximately 160 HIV-1 infected infants, children and adolescents aged ≥4 weeks to <18 years, and will evaluate the pharmacokinetic parameters, safety, tolerability and efficacy of Dolutegravir when administered both prior to starting, and in combination with OBT.

Study Population

  • Across all sites: 160 HIV-1 infected infants, children and adolescents.
  • Botswana sites (Gaborone & Molepolole): 5 HIV-1 infected infants, children and adolescents.

Study Duration:  3 years

Sponsor

  • The National Institute of Allergy and Infectious Diseases (NIAID)
  • The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Study Duration: 3 years

Study Status: Follow Up