OA04.05LB
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Trial design, enrollment status, demographics, and pharmacokinetics (PK) data from a blinded interim analysis from a phase 2a trial of Islatravir once monthly (QM) for HIV pre-exposure prophylaxis (PrEP)

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BACKGROUND: Islatravir (ISL, MK-8591) is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for the treatment and prevention of HIV-1. ISL is being evaluated as a once monthly tablet as PrEP. Trial design, enrollment demographics and status, and PK data from an ongoing phase 2a study are presented.
METHODS: This randomized, double-blind, placebo controlled, parallel-group, multi-center study is assessing the safety, tolerability and PK of oral ISL in adults aged 18 to 65 who have low-risk for HIV-1 acquisition. Participants were randomized in a 2:2:1 ratio into one of 3 groups receiving six doses of ISL 60 mg, ISL 120 mg, or placebo administered orally once monthly. ISL plasma levels were measured in all participants and ISL PK in peripheral blood mononuclear cells (PBMCs) and mucosal tissue (rectal, cervical and/or vaginal) was measured in a subset. Simulations using a previously developed population PK model were used to assess the interim observed plasma and PBMC PK data. Safety was assessed by adverse event (AE) reporting.
RESULTS: As of 17-September-2020, 171 of a planned 250 (68.4%) participants have been randomized and dosed (68.4% Female, median age 33 years, 70.8% white); 126 participants received all 6 planned doses, 38 completed the trial (through final follow-up visit) and 8 discontinued the trial early. Blinded safety monitoring suggests that study drugs were well tolerated. Interim PK analysis shows ISL-triphosphate trough concentrations following either 60 mg or 120 mg monthly doses were all above the pre-specified PK threshold for HIV-1 prophylaxis of 0.05 pmol/106 PBMCs. Preliminary PK analysis of biopsied tissues suggest rapid, sustained and adequate distribution of ISL to sampled tissues. ISL PK exhibited linear dose proportionality (Figure1).
CONCLUSIONS: This interim analysis suggests that monthly doses of ISL 60 mg and 120 mg achieved the pre-specified efficacious PrEP PK threshold.