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The first-in-human clinical trial of STP0404, a novel potent HIV-1 allosteric integrase inhibitor

Title
The first-in-human clinical trial of STP0404, a novel potent HIV-1 allosteric integrase inhibitor
Presenter
Xue Meng
Authors
X. Meng * (1), U.-I. Kim (1), Y. Donazzolo (2), B. Kim (3,4), K. Kim (1)
Institutions
(1) ST Pharm Co., Ltd., Seoul, Korea, The Republic of, (2) Eurofins Optimed S.A.S, Grenoble, France, (3) Emory University, School of Medicine, Department of Pediatrics, Atlanta, United States, (4) Children''s Healthcare of Atlanta, Center for Drug Discovery, Atlanta, United States

BACKGROUND: STP0404 is a novel HIV-1 allosteric integrase inhibitor with potent in vitro anti-HIV-1 activities, an in vitro resistance profile different from those of other catalytic-site integrase inhibitors, and favorable nonclinical safety and PK profiles.
METHODS: The safety and PK of STP0404 was evaluated in a double-blinded, placebo-controlled, randomized phase 1 clinical trial in healthy male adult volunteers with once daily regimen. Single and repeated administration with ascending doses (200, 400, 600 and 800 mg for SAD (Single Ascending Doses), 200 and 400 mg for 10 days for MAD (Multiple Ascending Doses)) and food effect (200 mg) were evaluated through this trial.
RESULTS: A total of 65 male subjects were enrolled (aged 18 to 45 years old). Most AEs were mild (75%, 21/28), headache (9/28) and diarrhea (5/28) were most frequently observed. No severe AE, SAE and withdrawn due to AE observed or occurred during the trial.
PK was linear but less-proportional over the dose ranged administered except for SAD 800 mg. Cmax were reached at 4 to 6 hours throughout the whole study. Accumulation ratio is around 1.3 at steady-state (D10). Food effect factor was around 1.5 to 2, and resulted in a lower variability in drug exposure. AUC0-Ï? and Cmax in plasma ranged from 23.6 h·µg/mL and 2.05 µg/mL at a 200 mg dose (fasted) to 67.7 h·µg/mL and 6.16 µg/mL at a 200 mg dose (fed, steady-state), respectively. Steady state was reached between Day 3 and Day 6, The mean Css,24h with a 200 mg dose was 1.37 µg/mL, approximately 600-fold of the protein-adjusted EC95 (0.0022 µg/mL).The elimination half-life were about 18 to 33 hours throughout the study. MAD 400 mg PK data will be ready before presentation.
CONCLUSIONS: STP0404 was well tolerated and its PK profile indicated a once-daily regimen at low dose level given after meal will achieve therapeutic concentrations. A Phase 2a clinical trial of STP0404 is planned to start at 3Q, 2022.

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