Study of ATI-450 Plus Methotrexate (MTX) vs MTX Alone in Patients With Moderate to Severe RA
Study Details
Study Description
Brief Summary
This is a Phase 2 study to investigate the safety, tolerability, PK, and PD of ATI-450 plus methotrexate versus methotrexate alone in patients with moderate to severe RA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a Phase 2, randomized, investigator and patient-blind, sponsor-unblinded, parallel group, placebo-controlled study to investigate the safety, tolerability, PK, and PD of ATI-450 plus methotrexate versus methotrexate alone in patients with moderate to severe RA with inadequate response to methotrexate. All subjects will be required to complete a safety follow up visit 30 days post last study medication administration.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ATI-450 plus Methotrexate ATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate |
Drug: ATI-450
Oral, small molecule MK2 inhibitor
Other Names:
Drug: Methotrexate
7.5 mg to 25 mg weekly
|
| Placebo Comparator: Placebo plus Methotrexate Placebo oral tablet BID with a stable weekly dose of Methotrexate |
Drug: Placebo oral tablet
Placebo tablet manufactured to match ATI-450 in appearance
Drug: Methotrexate
7.5 mg to 25 mg weekly
|
Outcome Measures
Primary Outcome Measures
- The primary outcome measure is the determination of the safety and tolerability of ATI-450 plus Methotrexate in patients with moderate to severe rheumatoid arthritis: Adverse Events (AEs) [114 days]
Adverse Events (AEs) will be coded with the Medical Dictionary for Regulatory Activities (MedDRA). AEs will be presented by system organ class and preferred term in frequency tables.
Secondary Outcome Measures
- Percent change in high sensitivity C-reactive protein (hsCRP) levels [Baseline through Day 114]
Median percent change from baseline in hsCRP over time
- Change from baseline in Disease Activity Score [Baseline through Day 114]
Mean change from baseline in Disease Activity Score using DAS28-CRP
- Change from baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Hand-Wrist Assessments [Baseline through Day 84]
Mean change from baseline in RAMRIS Hand-Wrist assessment of synovitis or osteitis
- Proportion of patients with American College of Rheumatology (ACR) 20/50/70 [Baseline through Day 114]
ACR20/50/70 will be calculated at each treatment visit and the proportion of subjects with a 20%, 50% and 70% improvement will be tabulated at each scheduled visit.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria.
-
DAS28-CRP ≥3.2 defined as moderate to high disease activity.
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Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints.
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hsCRP ≥5 mg/L at screening.
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Patients must have definitive intra-articular synovitis or osteitis defined as a score of 1 or greater on a Hand-Wrist MRI as assessed by central imaging reader (using RAMRIS).
-
On a stable MTX dose and a stable dose of folic or folinic acid prior to the screening visit.
Exclusion Criteria:
-
Patient has a current acute or chronic immunoinflammatory disease other than RA which may impact the course or assessment of RA.
-
Patient has an uncontrolled non-immunoinflammatory disease that may place the patient at increased risk during the study or impact the interpretation of results.
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History or evidence of active or latent tuberculosis.
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Active infection requiring treatment with antibiotics.
-
Blood pressure levels (in supine position after at least 5 minutes rest): <90 mmHg or
140 mmHg for systolic blood pressure or <40 mmHg or >90 mmHg for diastolic blood pressure.
-
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.
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Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of the screening visit.
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Patients with history of stroke.
-
Any joint procedure in the past 90 days prior to screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aclaris Investigational Site | Anniston | Alabama | United States | 36207 |
| 2 | Aclaris Investigational Site | Tampa | Florida | United States | 33613 |
| 3 | Aclaris Investigational Site | Atlanta | Georgia | United States | 30342 |
| 4 | Aclaris Investigational Site | Duncansville | Pennsylvania | United States | 16635 |
| 5 | Aclaris Investigational Site | Mesquite | Texas | United States | 75150 |
Sponsors and Collaborators
- Aclaris Therapeutics, Inc.
Investigators
- Study Director: David Gordon, Aclaris Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ATI-450-RA-201