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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Drug: ATI-450
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATI-450<br>ATI-450 50mg oral tablet BID | Drug: ATI-450<br>* Oral, small molecule MK2 inhibitor<br>* Other names: CDD-450;|
| Placebo Comparator: Placebo<br>Placebo oral tablet BID | Drug: Placebo Oral Tablet<br>* Placebo tablet manufactured to match ATI-450 in appearance<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Psoriatic