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Aclaris Therapeutics Announces Positive Results From Phase 1 Single and Multiple Ascending Dose Trial of ATI-450, an Investigational Oral MK2 Inhibitor
• Oral small molecule showed marked inhibition of TNFα, IL1β, IL8, and IL6• Preliminary data support progression to Phase 2a Proof of Concept Trials in
About this update from Aclaris Therapeutics, Inc.
[{"type":"text","content":"• Oral small molecule showed marked inhibition of TNFα, IL1β, IL8, and IL6• Preliminary data support progression to Phase 2a Proof of Concept Trials in Immuno-Inflammatory Diseases\n WAYNE, Pa., Jan. 09, 2020 (GLOBE NEWSWIRE) -- Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a physician-led biopharmaceutical company focused on immuno-inflammatory diseases, today announced positive results from ATI-450-PKPD-101, a Single Ascending Dose and Multiple Ascending Dose (SAD/MAD) Phase 1 clinical trial of the investigational compound ATI-450. Preliminary data demonstrated that ATI-450: resulted in marked inhibition of TNFα, IL1β, IL8, and IL6;was generally well-tolerated at all doses tested in the trial;had dose proportional pharmacokinetics (PK) with a terminal half-life of 9-12 hours; andhad no meaningful food effect or drug-drug interaction (DDI) with methotrexate. ATI-450-PKPD-101 was a first-in-human, randomized, observer-blind, placebo-controlled Phase 1 clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally administered ATI-450 in healthy subjects (n=77). The trial consisted of three parts: Single Ascending Dose (SAD) plus food effect (n=32, 8 subjects per dose cohort - 2 placebo, 6 active). A single dose of 10mg, 30mg, 50mg and 100mg was tested.Multiple Ascending Dose (MAD) (n=30, 10 subjects per dose cohort - 2 placebo, 8 active). 10mg BID, 30mg BID and 50mg BID doses were tested over 7 days of administration.Methotrexate DDI (n=15). Single 7.5-mg oral doses of methotrexate given alone or after ATI-450 50mg BID. No serious adverse events or severe adverse events were reported, and no adverse events led to discontinuation of the study medication. The most common adverse events (reported by 2 or more subjects who received ATI-450) observed during the trial were dizziness, headache, upper respiratory tract infection, constipation, nausea, and abdominal pain. All adverse events were mild. A trend of a decrease in absolute neutrophil count (ANC) was observed without correlated clinical sequelae. This effect is consistent with the pharmacodynamic profile of certain anti-TNF therapies1. Other laboratory findings were generally unremarkable. In this trial, ATI-450 had dose proportional pharmacokinetics with a terminal half-life of 9-12 hours in the MAD cohort on day 7. The PK profile ...