Clinical trial NCT04247815: Study of ATI-450 Plus Methotrexate (MTX) vs MTX Alone in Patients With Moderate to Severe RA
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Arthritis
Rheumatoid
Lead sponsor: Aclaris Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, investigator and patient-blind, sponsor-unblinded, parallel group.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.
* 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.

Primary outcomes:
measure: 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)
timeFrame: Baseline through Day 114
Secondary outcomes:
measure: Percent Change in (hsCRP) Levels Over Time
timeFrame: Baseline through Day 114
measure: Change From Baseline in Disease Activity Score
timeFrame: Baseline through Day 114
measure: Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time
timeFrame: Baseline through Day 114
measure: Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average)
timeFrame: Baseline through Day 84
measure: Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)
timeFrame: Baseline through Day 84
measure: Number and Percent of Patients Achieving ACR 20
timeFrame: Baseline through Day 114
measure: Number and Percent of Patients Achieving ACR 50
timeFrame: Baseline through Day 114
measure: Number and Percent of Patients Achieving ACR 70
timeFrame: Baseline through Day 114
measure: Assessment of ATI-450 Concentration (ng/mL)
timeFrame: Day 1 through Day Day 84
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Aclaris Investigational Site
state: Alabama
city: Tampa
country: United States
facility: Aclaris Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Aclaris Investigational Site
state: Georgia
city: Duncansville
country: United States
facility: Aclaris Investigational Site
state: Pennsylvania
city: Mesquite
country: United States
facility: Aclaris Investigational Site
state: Texas
Study officials:
affiliation: Aclaris Therapeutics
name: David Gordon
role: STUDY_DIRECTOR
References: