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

Aclaris Therapeutics, Inc.25 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

ATI-450DRUG

Oral, small molecule MK2 inhibitor

Placebo oral tabletDRUG

Placebo tablet manufactured to match ATI-450 in appearance

MethotrexateDRUG

7.5 mg to 25 mg weekly

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.

Locations (5)

Aclaris Investigational Site

Anniston, Alabama, United States

Aclaris Investigational Site

Tampa, Florida, United States

Aclaris Investigational Site

Atlanta, Georgia, United States

Aclaris Investigational Site

Duncansville, Pennsylvania, United States

Outcomes

Primary Outcomes

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)

Safety and tolerability reported as Adverse Events (AEs). AEs will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. AEs will be presented by system organ class and preferred term in frequency tables.

Time frame: Baseline through Day 114

Secondary Outcomes

Percent Change in (hsCRP) Levels Over Time

Median percent change from baseline in high sensitivity C-reactive protein (hsCRP) levels over time

Time frame: Baseline through Day 114

Change From Baseline in Disease Activity Score

The Disease Activity Score using 28 joint count C-reactive protein DAS28 (CRP) consists of a composite score of the following variables: tender joint count, swollen joint count, CRP, and Patient's Global Assessment of Disease Activity score. The following equation will be used to calculate the DAS28 (CRP): DAS28 (CRP) = 0.56 √TJC28 + 0.28√SJC28 + 0.36ln(CRP +1) + 0.014×(Patient's Global Assessment of Disease Activity) + 0.96, where: * TJC28 = number of joints tender out of 28 * SJC28 = number of joints swollen out of 28 * CRP = C-reactive protein * Patient's Global Assessment of Disease Activity on a 100 mm visual analog scale (VAS) recorded by the patient Interpretation of the DAS28 (CRP) disease activity measure is on a scale of 0 to 9.4, where: \<2.6 is considered remission, ≥2.6 to \<3.2 is considered low/minimal, ≥3.2 to ≤5.1 is considered moderate, and \>5.1 is considered high/severe.

Time frame: Baseline through Day 114

Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time

Number and Percent of Patients Achieving DAS28-CRP \<2.6 over time

Time frame: Baseline through Day 114

Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average)

Data from ClinicalTrials.gov

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