Study of ATI-450 Plus Methotrexate (MTX) vs MTX Alone in Patients With Moderate to Severe RA

A Phase 2a, Randomized, Investigator and Patient-blind, Sponsor-unblinded, Parallel Group, Placebo-controlled Study of ATI-450 Plus Methotrexate (MTX) vs MTX Alone in Patients With Moderate to Severe Active Rheumatoid Arthritis

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.

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.

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.
• Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints.
• hsCRP ≥5 mg/L at screening.
• 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.
• History or evidence of active or latent tuberculosis.
• 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.
• 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.
• Patients with history of stroke.
• Any joint procedure in the past 90 days prior to screening.