ATI-450 vs Placebo in Participants With Moderate to Severe Hidradenitis Suppurativa (HS)

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ATI-450 vs Placebo in Patients With Moderate to Severe Hidradenitis Suppurativa (HS)

This is a Phase 2a study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of ATI-450 vs placebo in patients with moderate to severe Hidradenitis Suppurativa (HS).

Study Overview

• Status: Completed
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: ATI-450

Detailed Description

This is a Phase 2a, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of ATI-450 vs placebo in patients with moderate to severe Hidradenitis Suppurativa (HS).

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • Aclaris Investigational Site
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Aclaris Investigational Site
  • California
    • Encino, California, United States, 91436
      • Aclaris Investigational Site
    • San Francisco, California, United States, 94115
      • Aclaris Investigational Site
    • Thousand Oaks, California, United States, 91436
      • Aclaris Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Aclaris Investigational Site
    • Hollywood, Florida, United States, 33021
      • Aclaris Investigational Site
    • Tampa, Florida, United States, 33613
      • Aclaris Investigational Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Aclaris Investigational Site
    • Sandy Springs, Georgia, United States, 30328
      • Aclaris Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Aclaris Investigational Site
  • Michigan
    • Fort Gratiot, Michigan, United States, 48059
      • Aclaris Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Aclaris Investigational Site
  • Ohio
    • Athens, Ohio, United States, 45701
      • Aclaris Investigational Site
    • Mason, Ohio, United States, 45040
      • Aclaris Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Aclaris Investigational Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Aclaris Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Aclaris Investigational Site
  • Texas
    • Houston, Texas, United States, 77054
      • Aclaris Investigational Site
    • Sugar Land, Texas, United States, 77478
      • Aclaris Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to comprehend and be willing to sign the Institutional Review Board (IRB)-approved participant informed consent form prior to administration of any study-related procedures.
• Participant must have stable HS.
• Total abscesses and/or nodule (AN) count of ≥5 at Baseline visit.
• HS lesions present in at least 2 distinct anatomical areas at Screening and Baseline.

Exclusion Criteria:

• Participant has a history of active skin disease other than HS that could interfere with the assessment of HS.
• Participant has an uncontrolled non-immunoinflammatory disease that may place the participant at increased risk during the study or impact the interpretation of results, e.g., previous malignancy, previous venous thromboembolism.
• Participant has experience with >2 biologics, >1 Janus kinase (JAK) inhibitor, or a combination of 1 biologic experience and 1 JAK inhibitor.
• Are currently receiving corticosteroids at doses greater than 10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of the Screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; Placebo oral tablet BID	Drug: Placebo oral tablet; Placebo tablet manufactured to match ATI-450 in appearance; Other Names: Placebo
Experimental: ATI-450; ATI-450 50 milligrams (mg) oral tablet twice daily (BID)	Drug: ATI-450; Oral, small molecule MK2 inhibitor; Other Names: Zunsemetinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Abscess and Inflammatory Nodule (AN) Count at Week 12	AN count was the sum of number of abscess and inflammatory nodules across anatomical regions. The least square (LS) mean change from baseline in the count at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 12	HiSCR50 Achiever was defined as a participant having a ≥50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase in the number of abscesses, and no increase in the number of draining fistula counts from baseline. A participant was considered an achiever only if all 3 criteria mentioned above were fulfilled. Model-based estimates and 90% confidence intervals (CIs) were produced. Firth's penalized likelihood logistic regression model with fixed effects for treatment and baseline count of inflammatory abscesses and nodules was used.	Week 12
Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS-4) at Week 12	The IHS-4 is a validated tool used to access the HS severity and is calculated based on the clinical signs of HS: inflammatory nodules, abscesses and draining tunnels (fistulas and sinuses). The IHS-4 score = (number of nodules multiplied by 1) + (number of abscesses multiplied by 2) + (number of draining tunnels [fistulas/sinuses] multiplied by 4). Mild HS is a score of 3 or less, moderate HS is a score of 4-10, and severe HS is a score of 11 or higher. A decrease in score means less severity.	Baseline, Week 12
Percentage of Participants Achieving NRS30	NRS30 Achiever was defined as participants achieving at least a 30% reduction from baseline in Patient's Global Assessment of Skin Pain (PGA-SP) and at least 1 unit reduction from baseline in PGA-SP at Week 12 among participants with baseline PGA-SP ≥3. Model-based estimates and 90% CIs were produced. Firth's penalized likelihood logistic regression model with fixed effects for treatment and baseline PGA-SP was used.	Week 12
Change From Baseline in Hidradenitis Suppurativa-Physician Global Assessment (HSPGA) at Week 12	In the HS-PGA scale, the Investigators rated the counts of nodules (inflammatory and non-inflammatory) abscesses and fistulas (both draining and nondraining) and assigned a participant to 1 of 6 categories ranging from clear (0) to very severe (5). A decrease in score means a better outcome.	Baseline, Week 12
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12	The DLQI is a 10-item validated questionnaire used to assess the impact of HS disease symptoms and treatment on quality of life (QoL). It consists of questions including a single "yes/no" question and questions with possible responses of "not at all," "a little," "a lot," or "very much." These questions evaluate the impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each question was scored using a 4-point scale ranging from 0 to 3 based on a participant's response: not at all/not relevant (0), a little (1), a lot (2) and very much (3). The total score of the DLQI ranged from 0 to 30 and was calculated by adding up the scores from each question. The higher the score, the greater the impact on a participant's QoL.	Baseline, Week 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs are defined as AEs with an onset date on or after the date of first administration of study drug and before the date of last administration of study drug + 30 days. A summary of non-serious AEs and serious AEs, regardless of causality is located in Reported AEs section.	Baseline through Day 115
ATI-450 and Metabolite (CDD-2164) Concentrations		2 hours postdose on Days 1, 8, and 85

Collaborators and Investigators

• Sponsor: Aclaris Therapeutics, Inc.
• Investigators: Study Director: Ajay Aggarwal, Aclaris Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2021
• Primary Completion (Actual): December 23, 2022
• Study Completion (Actual): January 24, 2023

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: HS; Acne inversa; Hidradenitis; Suppurativa
• Additional Relevant MeSH Terms: Infections; Skin Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Sweat Gland Diseases; Skin Diseases, Bacterial; Skin Diseases, Infectious; Suppuration; Skin and Connective Tissue Diseases; Hidradenitis Suppurativa; Hidradenitis
• Other Study ID Numbers: ATI-450-HS-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No