Study of ATI-450 vs Placebo in Patients With Moderate to Severe Psoriatic Arthritis

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Zunsemetinib vs Placebo in Patients With Moderate-to-Severe Active Psoriatic Arthritis

This is a Phase 2a study to investigate the efficacy, safety, tolerability, PK, and PD of ATI-450 versus placebo in patients with moderate to severe psoriatic arthritis.

Study Overview

• Status: Terminated
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: ATI-450; Drug: Placebo Oral Tablet

Detailed Description

This is a Phase 2a, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety, tolerability, PK, and PD of ATI-450 versus placebo in patients with moderate to severe psoriatic arthritis.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Białystok, Poland, 15-707
    • Aclaris Investigational Site
  • Bydgoszcz, Poland, 85-168
    • Aclaris Investigational Site
  • Częstochowa, Poland, 42-200
    • Aclaris Investigational Site
  • Katowice, Poland, 40-040
    • Aclaris Investigational Site
  • Katowice, Poland, 40-081
    • Aclaris Investigational Site
  • Kraków, Poland, 30-363
    • Aclaris Investigational Site
  • Kraków, Poland, 30-510
    • Aclaris Investigational Site
  • Olsztyn, Poland, 10-341
    • Aclaris Investigational Site
  • Poznań, Poland, 60-702
    • Aclaris Investigational Site
  • Stalowa Wola, Poland, 37-450
    • Aclaris Investigational Site
  • Szczecin, Poland, 70-332
    • Aclaris Investigational Site
  • Toruń, Poland, 87-100
    • Aclaris Investigational Site
  • Warszawa, Poland, 04-141
    • Aclaris Investigational Site
  • Wrocław, Poland, 50-381
    • Aclaris Investigational Site
• United States
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Aclaris Investigational Site
    • Tampa, Florida, United States, 33613
      • Aclaris Investigational Site
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Aclaris Clinical Operations
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Aclaris Clinical Operations
  • Ohio
    • Perrysburg, Ohio, United States, 43551
      • Aclaris Investigational Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Aclaris Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Aclaris Investigational Site
  • Texas
    • Mesquite, Texas, United States, 75150
      • Aclaris Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of PsA with symptom onset at least 6 months before the Screening Visit and fulfilment of the Classification Criteria for PsA.

• Patient has moderate-to-severe PsA at Screening and Randomization Visits defined as

  • ≥3 tender joints (based on 68 joint counts) and
  • ≥3 swollen joints (based on 66 joint counts).
• Diagnosis of active plaque psoriasis or documented history of plaque psoriasis.

Exclusion Criteria:

• Any arthritis with onset before age 17 years, or current diagnosis of inflammatory joint disease other than PsA, or other immunological disease (including, but not limited to rheumatoid arthritis, gout, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus).
• Patient has an uncontrolled non-immunoinflammatory disease that may place the patient at increased risk during the study or impact the interpretation of results, eg, cirrhosis, previous malignancy, previous venous thromboembolism.
• Any clinically significant laboratory abnormality that would affect interpretation of study data or safety of the patient's participation in the study, per judgment of the investigator.

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: ATI-450; ATI-450 50mg oral tablet BID	Drug: ATI-450; Oral, small molecule MK2 inhibitor; Other Names: CDD-450
Placebo Comparator: Placebo; Placebo oral tablet BID	Drug: Placebo Oral Tablet; Placebo tablet manufactured to match ATI-450 in appearance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients achieving ACR20 at Week 12	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with ACR 50/70 at Week 12	Baseline to Week 12
Proportion of patients with ACR 20/50/70 response at weeks 2, 4, 6, 8	Baseline to Week 12
Change from baseline in tender joint count 68 at weeks 1, 2, 4, 6, 8, 12	Baseline to Week 12
Change from baseline in swollen joint count 66 at weeks 1, 2, 4, 8, 12	Baseline to Week 12
Change from baseline in Health Assessment Questionnaire - Disability Index at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in patient's global assessment of disease activity at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in physician's global assessment of disease activity at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in Patients Pain VAS assessment at Weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in high sensitivity C-reactive protein (hs-CRP) at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in Leeds Enthesitis Index over 12 weeks	Baseline to Week 12
Change from baseline in Leeds Dactylitis Index over 12 weeks	Baseline to Week 12
Proportion of patients achieving at least a 30% reduction and at least 1 unit reduction from Baseline in the numerical rating scale (NRS30) in Patient's Daily Assessment of Skin Pain at Weeks 2, 4, 8, 12 among patients with Baseline NRS ≥3	Baseline to Week 12
Proportion of patients achieving a sIGA of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline among those with a baseline investigator's global assessment of at least 3 over 12 weeks	Baseline to Week 12
Proportion of patients achieving MDA at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in DAS28CRP at Weeks 2, 4, 8, 12	Baseline to Week 12
Psoriasis Area Severity Index (PASI) 50/75/90 response (for patients with ≥3% body surface area psoriasis at baseline) at Week 12	Baseline to Week 12
Mean change from baseline in PASI score at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in Short-Form-36 Physical Component Summary at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire at weeks 2, 4, 8, 12	Baseline to Week 12
Change from baseline in Self-Assessment of Psoriasis Symptoms Questionnaire at weeks 2, 4, 8, 12	Baseline to Week 12
Type and frequency of adverse events	Baseline to Week 12
Type and frequency of serious adverse events	Baseline to Week 12
Zunsemetinib trough concentration ng/mL	Baseline to Week 12
CDD-2164 metabolite trough concentration ng/mL	Baseline to Week 12
Zunsemetinib peak concentration (Cmax) ng/mL	Baseline to Week 12
CDD-2164 metabolite peak concentration (Cmax) ng/mL	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Aclaris Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Actual): December 6, 2023
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: August 19, 2022
• First Posted (Actual): August 23, 2022

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Arthritis; Psoriatic
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: ATI-450-PsA-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