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Completed

NCT Number: NCT04247815

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

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Aclaris Investigational Site, Anniston, Alabama, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ATI-450

Drug

Oral, small molecule MK2 inhibitor

Other names: CDD-450

Placebo oral tablet

Drug

Placebo tablet manufactured to match ATI-450 in appearance

methotrexate

Drug

7.5 mg to 25 mg weekly

Primary outcomes

  1. 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)

    Time frame: Baseline through Day 114

    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.

Secondary outcomes

  1. Percent Change in (hsCRP) Levels Over Time

    Time frame: Baseline through Day 114

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

  2. Change From Baseline in Disease Activity Score

    Time frame: Baseline through Day 114

    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.

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

    Time frame: Baseline through Day 114

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

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

    Time frame: Baseline through Day 84

    Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) uses integer scales to measure the severity of disease at each bone or joint of interest in the hand and wrist, with separate scores given for osteitis and synovitis.

    Osteitis was scored at 25 bone locations: distal radius and ulna, 8 carpal bones (trapezium, trapezoid, capitate, hamate, pisiform, scaphoid, lunate, and triquetrum, as well as the 5 metacarpal bases), 5 metacarpal heads, and 5 proximal phalangeal bases.

    Score Definition

    0 No osteitis

    • 1-33% involvement of original articular bone
    • 34-67% involvement of original articular bone
    • 68-100% involvement of original articular bone

    Synovitis was scored at the following 8 joint locations: distal radioulnar joint, radiocarpal joint, intercarpal / carpometacarpal joints 2-5, and 5 metacarpophalangeal (MCP) joints.

    Score Definition

    0 No synovitis

    • 1-33% volume enhancement
    • 34-67% volume enhancement
    • 68-100% volume enhancement

  5. Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)

    Time frame: Baseline through Day 84

    Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) uses integer scales to measure the severity of disease at each bone or joint of interest in the hand and wrist, with separate scores given for osteitis and synovitis.

    Osteitis was scored at 25 bone locations: distal radius and ulna, 8 carpal bones (trapezium, trapezoid, capitate, hamate, pisiform, scaphoid, lunate, and triquetrum, as well as the 5 metacarpal bases), 5 metacarpal heads, and 5 proximal phalangeal bases.

    Score Definition

    0 No osteitis

    • 1-33% involvement of original articular bone
    • 34-67% involvement of original articular bone
    • 68-100% involvement of original articular bone

    Synovitis was scored at the following 8 joint locations: distal radioulnar joint, radiocarpal joint, intercarpal / carpometacarpal joints 2-5, and 5 metacarpophalangeal (MCP) joints.

    Score Definition

    0 No synovitis

    • 1-33% volume enhancement
    • 34-67% volume enhancement
    • 68-100% volume enhancement

  6. Number and Percent of Patients Achieving ACR 20

    Time frame: Baseline through Day 114

    American College of Rheumatology (ACR) 20 will be calculated at each treatment visit and the number and percent of subjects with a 20% improvement will be tabulated at each scheduled visit.

  7. Number and Percent of Patients Achieving ACR 50

    Time frame: Baseline through Day 114

    American College of Rheumatology (ACR) 50 will be calculated at each treatment visit and the number and percent of subjects with a 50% improvement will be tabulated at each scheduled visit.

  8. Number and Percent of Patients Achieving ACR 70

    Time frame: Baseline through Day 114

    American College of Rheumatology (ACR) 70 will be calculated at each treatment visit and the number and percent of subjects with a 70% improvement will be tabulated at each scheduled visit.

  9. Assessment of ATI-450 Concentration (ng/mL)

    Time frame: Day 1 through Day Day 84

Sponsors and collaborators

Lead sponsor

Aclaris Therapeutics, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Jan 30, 2020
Registry last updated
Mar 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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