Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid, Arthritis, RA
Brief summary
This study evaluates ATI-450 plus MTX versus placebo plus MTX in participants with moderate to severe active RA who have had an inadequate response to MTX alone.
Detailed description
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 MTX versus placebo plus MTX in participants with moderate to severe active RA who have had an inadequate response to MTX alone.
Interventions
DRUGATI-450 50 mg oral tablet BID
Oral, small molecule MK2 inhibitor
DRUGPlacebo oral tablet
Placebo tablet manufactured to match ATI-450 in appearance
DRUGMethotrexate
15 mg to 25 mg weekly
DRUGATI-450 20 mg oral tablet BID
Oral, small molecule MK2 inhibitor
Sponsors
Aclaris Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Able to comprehend and be willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved participant 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 participant at increased risk during the study or impact the interpretation of results (eg, previous malignancy, recurrent infection, previous venous thromboembolism). * Participant 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients achieving ACR20 at Week 12 | Baseline to Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Proportion of patients achieving ACR50/70 at Week 12 | Baseline to Week 12 |
| 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 |
| Percent change from baseline in hsCRP level over time | Up to 30 days after 12 weeks of treatment |
Countries
Bulgaria, Czechia, Poland, United States
Outcome results
None listed