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Selection of cabotegravir dosing regimens for HIV treatment and pre-exposure prophylaxis (PrEP) in adolescents by Leveraging adult data

Title
Selection of cabotegravir dosing regimens for HIV treatment and pre-exposure prophylaxis (PrEP) in adolescents by Leveraging adult data
Presenter
Mark Baker
Authors
K. Han (1), N. Goyal (1), S. Ford (2), S.Y.A. Cheung (1), L. Tan (3), C. McCoig (4), P. Patel (5), E. Capparelli (6), B. Best (6), M. Marzinke (7), C. Bolton Moore (8,9), A.H. Gaur (10), C. Harrington (5), D. Izard (1), J. Huang (1), M. Baker * (11)
Institutions
(1) GlaxoSmithKline, Collegeville, United States, (2) GlaxoSmithKline, Research Triangle Park, United States, (3) ViiV Healthcare, Brentford, United Kingdom, (4) ViiV Healthcare, Madrid, Spain, (5) ViiV Healthcare, Research Triangle Park, United States, (6) University of California San Diego, La Jolla, United States, (7) Johns Hopkins University, Baltimore, United States, (8) Centre for Infectious Disease Research in Zambia, Lusaka, Zambia, (9) University of Alabama at Birmingham, Birmingham, United States, (10) St. Jude Children''s Research Hospital, Memphis, United States, (11) ViiV Healthcare, Nyon, Switzerland

BACKGROUND: Cabotegravir (CAB) is the first complete long-acting (LA) regimen for HIV treatment (with rilpivirine) in adults and PrEP in adults and adolescents ('¥35kg). CAB LA is an important alternative to daily oral regimens for adolescents. Oral and LA CAB pharmacokinetics (PK) and safety were characterized in virologically-suppressed adolescents ('¥35kg) on stable combination antiretroviral therapy in the ongoing MOCHA study. Population PK (PPK) modelling was used to support extrapolation from adults to adolescents and bridge dose regimens and therapeutic use.
METHODS: Interim PK from MOCHA (8 adolescents) was compared to adult PK to establish PK similarity and determine feasibility of extrapolation. Adolescent PK profiles following monthly and every-2-months regimens were simulated by incorporating adolescent weight and BMI in a previously developed adult PPK model, and compared to adult PK targets.
RESULTS: Observed and predicted adolescent PK were similar to that in adults receiving treatment or PrEP regimens (Figure 1). Adult regimens in adolescents had resulting PK most similar to adults with similar weight range. PPK model accurately predicted PK from adolescents '¥35kg and bridged dose frequency and HIV-infection status. The observed and simulated data demonstrated that adolescents, receiving adult CAB regimens, remained above PK targets observed in adults and below safety thresholds (Figure 2).



CONCLUSIONS: Robust modelling and simulation approaches, combined with adolescent PK data from MOCHA, allowed bridging and extrapolation across several factors, and inform future study design. The consistency of adolescent and adult PK supports the use of adult CAB regimens in adolescents '¥12 years and '¥35 kg.

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