ATI-450 Plus MTX Versus Placebo Plus MTX in Patients With Moderate to Severe Active RA

Study Overview
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Brief Summary
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ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Patients with Moderate to Severe Active Rheumatoid Arthritis (RA) who have had an Inadequate Response to MTX Alone

Detailed Description
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This is a Phase 2b, Randomized, Multicenter, Double-blind, Parallel Group, Placebo Controlled, Dose Ranging Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Patients with Moderate to Severe Active Rheumatoid Arthritis (RA) who have had an Inadequate Response to MTX Alone

Official Title
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ATI-450 Plus MTX Versus Placebo Plus MTX in Patients With Moderate to Severe Active RA Who Have Had an Inadequate Response to MTX Alone

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: ATI-450 50mg oral tablet BID
* Drug: Placebo oral tablet
* Drug: Methotrexate
* Drug: ATI-450 20mg oral tablet BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and be willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved patient ICF prior to administration of any study-related procedures. Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Have active moderate to severe RA at Screening. A minimum of 12 weeks on MTX with a stable MTX dose. Exclusion Criteria: Current acute or chronic immunoinflammatory disease other than RA which may impact the course or assessment of RA. Uncontrolled non-immunoinflammatory disease that may place the patient at increased risk during the study or impact the interpretation of results (eg, previous malignancy, recurrent infection, previous venous thromboembolism). Patient has experience with > 2 biologics, > 1 JAK inhibitor, or a combination of 1 biologic experience and 1 JAK inhibitor. Currently receiving corticosteroids at doses > 10 mg/day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of screening.

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 20mg BID plus Methotrexate<br>ATI-450 20mg oral tablet BID with a stable weekly dose of Methotrexate | Drug: Methotrexate<br>* 15 mg to 25 mg weekly<br>Drug: ATI-450 20mg oral tablet BID<br>* Oral, small molecule MK2 inhibitor<br>* Other names: zunsemetinib;|
| Experimental: ATI-450 50mg BID plus Methotrexate<br>ATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate | Drug: ATI-450 50mg oral tablet BID<br>* Oral, small molecule MK2 inhibitor<br>* Other names: zunsemetinib;Drug: Methotrexate<br>* 15 mg to 25 mg weekly<br>|
| Placebo Comparator: Placebo plus Methotrexate<br>Placebo oral tablet BID with a stable weekly dose of Methotrexate | Drug: Placebo oral tablet<br>* Placebo tablet manufactured to match ATI-450 in appearance<br>Drug: Methotrexate<br>* 15 mg to 25 mg weekly<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 achieving ACR50/70 at Week 12 |  | Baseline to Week 12 | 
| Proportion of patients achieving ACR20/50/70 over time |  | Up to 12 Weeks | 
| Mean change from baseline in DAS28-CRP over time |  | Up to 12 Weeks | 
| Proportion of patients achieving DAS28-CRP remission (score < 2.6) over time |  | Up to 12 Weeks | 
| Proportion of patients achieving DAS28-CRP low disease activity (score ≤ 3.2) over time |  | Up to 12 Weeks | 
| Mean change from baseline in CDAI over time |  | Up to 12 Weeks | 
| Proportion of patients achieving CDAI remission (score ≤ 2.8) over time |  | Up to 12 Weeks | 
| Percent change from baseline in hsCRP level over time |  | Up to 30 days after 12 weeks of treatment | 
| Health Assessment Questionnaire-Disability Index (HAQ-DI) score over time |  | Up to 12 Weeks | 
| Short Form Health Survey version-2.0 (SF-36v2) score over time |  | Up to 12 Weeks | 
| Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) score over time |  | Up to 12 Weeks | 
| Incidence of adverse events (AEs), serious AEs (SAEs), laboratory value abnormalities, electrocardiogram (ECG) abnormalities, vital signs abnormalities |  | Baseline to Week 12 | 
| Trough ATI-450 and metabolite (CDD-2164) concentrations at clinic visits (trough and 2-hour post dose will be collected). |  | Study Days 1, 8, and 85 | 

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