WAYNE, PA — Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, announced positive preliminary topline results from its first in human Phase 2a, multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial to evaluate the efficacy, safety, tolerability and pharmacokinetics of ATI-1777, an investigational topical “soft” JAK 1/3 inhibitor, in 50 subjects with moderate to severe atopic dermatitis (AD) (ATI-1777-AD-201). ATI-1777 is the second compound generated from Aclaris’ proprietary KINect® drug discovery platform to demonstrate positive proof of concept in clinical trials.
“We are very pleased that we achieved positive results in this trial of ATI-1777 in subjects with moderate to severe AD with minimal systemic exposure to drug,” said Dr. David Gordon, Chief Medical Officer at Aclaris. “Our approach to treating patients with moderate to severe atopic dermatitis is particularly relevant in light of some of the potential safety concerns with oral therapies. We look forward to advancing ATI-1777 into the next phase of clinical development.”
In the trial, which consisted of a 4-week treatment period and a 2-week follow-up period during which no treatment was given, 50 subjects with moderate to severe AD were randomized in a 1:1 ratio into one of two arms: ATI-1777 topical solution 2.0% w/w or vehicle applied twice daily. One of the key objectives of this first in human trial was to assess the “soft” aspect of this topical JAK inhibitor compound in subjects with moderate to severe atopic dermatitis. A preliminary analysis of pharmacokinetic plasma samples in the ATI-1777 arm showed greater than 86% of the plasma samples had concentrations below 1 ng/ml and mean drug levels in the ATI-1777 arm (as a group) were not greater than 5% of the IC50 of ATI-1777.
The primary efficacy endpoint of this trial was the percent change from baseline in the modified Eczema Area and Severity Index (mEASI) score at week 4. The mEASI is a modified measure of EASI which excludes evaluation of the body areas that were not treated in the trial (i.e., the head, palms of hands, soles of feet, groin, or genitalia). Only the primary efficacy endpoint was powered to detect a statistically significant outcome.
The Full Analysis Set (FAS), which was comprised of subjects randomized and documented to have received at least one dose of trial medication, was used for the primary endpoint. Two subjects in the ATI-1777 arm were excluded from the FAS analysis on the basis that they were lost to follow up after the baseline visit and did not have a formal record of having received at least one dose of trial medication. Key secondary efficacy endpoints, which were not powered for statistical significance, included the proportion of subjects who achieved 50% improvement in mEASI score (mEASI-50) within 4 weeks of the start of treatment, the change from baseline in the Investigator’s Global Assessment (IGA) score at each trial visit, IGA responder analysis, change from baseline in Body Surface Area (BSA) affected by AD at each trial visit, and change from baseline in peak pruritus numerical rating scale (PP-NRS) score over time.
The FAS was comprised of 23 and 25 subjects in the ATI-1777 and vehicle arms, respectively. The trial achieved its primary endpoint with a high degree of statistical significance (p<0.001) (one-sided p-value), which corresponded to a 74.4% reduction in mEASI score from baseline at week 4 in subjects applying ATI-1777 compared to a 41.4% reduction in subjects applying vehicle. In addition, a post-hoc analysis which included the two randomized subjects not in the FAS, using their baseline mEASI score carried forward to day 28, was statistically significant (p=0.002) (one-sided p-value).
In addition, positive trends in favor of ATI-1777 were observed in key secondary efficacy endpoints, such as improvement in itch, percent of mEASI-50 responders, IGA responder analysis, and reduction in BSA impacted by disease.
ATI-1777 was generally well tolerated. Nine subjects in each arm reported treatment-emergent adverse events (9/23 and 9/25 in the ATI-1777 and vehicle arm, respectively). No serious adverse events were reported. One treatment-related adverse event (AE), application site pruritus, was reported in one subject in the ATI-1777 arm. The most common AEs (reported in ≥2 subjects in the trial) were increased blood creatinine phosphokinase and headache in subjects in the ATI-1777 arm and urinary tract infection (one each in the ATI-1777 and the vehicle arm); none of these AEs in the ATI-1777 arm were determined by the clinical trial investigators to be related to ATI-1777. There were no reports of thrombosis in the trial. In the FAS analysis, two subjects from the ATI-1777 arm withdrew from the trial (one lost to follow up, one withdrew consent), while seven subjects withdrew from the vehicle arm (three due to AEs and four withdrew consent).
Final trial results will be submitted for publication in a peer-reviewed scientific journal.
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