ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201

  • JID Innov. 2023 Nov 28;4(2):100251. doi: 10.1016/j.xjidi.2023.100251.
Paul Changelian  1 ,  Canxin Xu  1 ,  Steve Mnich  1 ,  Heidi Hope  1 ,  Kourtney Kostecki  1  2 ,  Jeff Hirsch  1 ,  Chin-Yi Loh  1  3 ,  David Anderson  1 ,  James Blinn  1 ,  Susan Hockerman  1 ,  Evan Dick  1  4 ,  Walter Smith  1 ,  Joseph Monahan  1 ,  Tooraj Raoof  5 ,  Seth Forman  6 ,  David Burt  1 ,  Brad Barnes  1 ,  David Gordon  1  7 ,  Neal Walker  1 ,  John Sudzina  1 ,  Stephen Tucker  1 ,  Jon Jacobsen  1
Affiliations
  • 1. Aclaris Therapeutics, Chesterbrook, Pennsylvania, USA.
  • 2. Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • 3. Miguel Hernández University of Elche, Alicante, Spain.
  • 4. Research and Development, Context Therapeutics, Philadelphia, Pennsylvania, USA.
  • 5. Raoof MD Dermatology, Encino, California, USA.
  • 6. CenExel FCR, Tampa, Florida, USA.
  • 7. Clinical Development, Immunology, Johnson & Johnson, West Chester, Pennsylvania, USA.
PMID: 38299059 DOI: 10.1016/j.xjidi.2023.100251
Abstract

Introduction: Atopic dermatitis, a chronic, pruritic skin disease, affects 10-30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective JAK1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited JAK1/3 with limited systemic exposure and without any adverse effects.

Primary objective: The primary goal of this study was to assess the preliminary clinical efficacy of ATI-1777 topical solution in adults with moderate or severe atopic dermatitis.

Design: ATI-1777-AD-201, a phase 2a, first-in-human, randomized, double-blind, vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48 participants with atopic dermatitis over 4 weeks.

Primary endpoint: The primary endpoint was a reduction of a modified Eczema Area and Severity Index score from baseline.

Results: Reduction was significantly greater in the ATI-1777-treated group on day 28 than in vehicle-treated group (percentage reduction from baseline = 74.45% [standard error = 6.455] and 41.43% [standard error = 6.189], respectively [P < .001]). Average plasma concentrations of ATI-1777 were <5% of the half-maximal inhibitory concentration of ATI-1777 for inhibiting JAK1/3. No deaths or serious adverse events were reported.

Conclusion: Topical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of atopic dermatitis.

Trial registration: The study was registered at ClinicalTrials.gov with the number NCT04598269.

Keywords
Hematopoiesis; Metabolism; Porcine model; Screening; Skin.
Products