A-LB-IAS2021-02361Safety and pharmacokinetics of oral islatravir once monthly for HIV pre-exposure prophylaxis (PrEP): week 24 analysis of a phase 2a trial


S. Hillier * (1), L.-G. Bekker (2), S.A. Riddler (3), C.W. Hendrix (4), S. Badal-Faesen (5), S. Rasmussen (6), H. Schwartz (7), P. Macdonald (2), J. Lombaard (8), Y. Caraco (9), A. Peer (10), M. Patel (11), B. Evans (11), B. Homony (11), K. Nedrow (11), V. Teal (11), P. Hwang (11), M.N. Robertson (11), R.M. Plank (11) - (1) Magee-Women''s Research Institute & Foundation, Pittsburgh, United States, (2) Desmond Tutu HIV Centre, Cape Town, South Africa, (3) University of Pittsburgh, Pittsburgh, United States, (4) John Hopkins Hospital, Baltimore, United States, (5) University of the Witwatersrand, Clinical HIV Research Unit, Johannesburg, South Africa, (6) Celerion, Lincoln, United States, (7) Research Centers of America, Hollywood, United States, (8) Josha Research, Bloemfontein, South Africa, (9) Hadassah Medical Center, Jerusalem, Israel, (10) Rambam Health Care Campus, Haifa, Israel, (11) Merck & Co., Inc., Kenilworth, United States


BACKGROUND: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor in development for prevention of HIV-1. Phase 3 trials of oral ISL 60mg once monthly (QM) are enrolling. We present unblinded safety and pharmacokinetic (PK) results through Week 24 of an ongoing phase 2a trial of monthly ISL for PrEP.
METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicenter trial (NCT04003103) assesses the safety, tolerability, and PK of oral ISL in adults (age 18-65 years) at low-risk for HIV-1 acquisition. Participants were randomly assigned (2:2:1) to receive 6 QM doses of ISL 60mg, ISL 120mg, or matching placebo. ISL in plasma was measured in all participants; ISL-triphosphate (ISL-TP) in peripheral blood mononuclear cells (PBMCs) was measured in a subset. Safety assessments included adverse event (AE) reporting and laboratory results monitoring. Aggregate safety results through 05-Apr-2021 are reported here; unblinded safety results for all participants through Week 24 will be available for presentation.
RESULTS: Of 242 participants randomized (median age 31 years, 67% female, 53% white, 42% Black or African American),189 completed dosing, 15 discontinued study intervention, and 38 were ongoing as of 05-Apr-2021. AEs were reported by 60% of participants; the most common AEs were headache (9%), diarrhea (5%), and nausea (5%). AEs considered drug-related by the investigator were reported in 15% of participants; all drug-related AEs were mild or moderate (DAIDS grade 1-2). Two participants discontinued study drug due to drug-related AEs (mild foreign body sensation in throat; moderate rash and pruritis). Two serious AEs (including one death) were reported; neither was considered drug-related. Grade 3-4 laboratory values were uncommon (Table). ISL-TP trough concentrations after both ISL 60mg and 120mg QM dosing remained above 0.05 pmol/106 PBMCs, the pre-specified threshold for PrEP.
CONCLUSIONS: Oral ISL 60mg and 120mg QM were well-tolerated over 24 weeks and achieved the pre-specified PK threshold for HIV-1 prevention.