ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Participants With Moderate to Severe Active Rheumatoid Arthritis (RA)

September 3, 2024 updated by: Aclaris Therapeutics, Inc.

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 Methotrexate (MTX) Versus Placebo Plus MTX in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

251

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4000
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4001
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4002
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4004
        • Aclaris Investigational Site
      • Sofia, Bulgaria, 1336
        • Aclaris Investigational Site
      • Sofia, Bulgaria, 1431
        • Aclaris Investigational Site
      • Sofia, Bulgaria, 1606
        • Aclaris Investigational Site
      • Varna, Bulgaria, 9000
        • Aclaris Investigational Site
  • Czechia
      • Brno, Czechia, 615 00
        • Aclaris Investigational Site
      • Hlučín, Czechia, 748 01
        • Aclaris Investigational Site
      • Ostrava, Czechia, 702 00
        • Aclaris Investigational Site
      • Pardubice, Czechia, 530 02
        • Aclaris Investigational Site
      • Praha, Czechia, 128 50
        • Aclaris Investigational Site
      • Praha, Czechia, 140 00
        • Aclaris Investigational Site
      • Uherské Hradiště, Czechia, 686 01
        • Aclaris Investigational Site
  • Poland
      • Białystok, Poland, 15-297
        • Aclaris Investigational Site
      • Białystok, Poland, 15-879
        • Aclaris Investigational Site
      • Dąbrówka, Poland, 62-069
        • Aclaris Investigational Site
      • Kraków, Poland, 30-363
        • Aclaris Investigational Site
      • Lublin, Poland, 20-607
        • Aclaris Investigational Site
      • Nowa Sól, Poland, 67-100
        • Aclaris Investigational Site
      • Poznań, Poland, 60-218
        • Aclaris Investigational Site
      • Poznań, Poland, 60-446
        • Aclaris Investigational Site
      • Poznań, Poland, 61-397
        • Aclaris Investigational Site
      • Sochaczew, Poland, 96-500
        • Aclaris Investigational Site
      • Toruń, Poland, 87-100
        • Aclaris Investigational Site
      • Warszawa, Poland, 04-141
        • Aclaris Investigational Site
      • Wrocław, Poland, 52-442
        • Aclaris Investigational Site
    • Lubelski
      • Tomaszów Lubelski, Lubelski, Poland, 22-600
        • Aclaris Investigational Site
    • Lubelskie
      • Lublin, Lubelskie, Poland, 20-362
        • Aclaris Investigational Site
    • Malopolskie
      • Kraków, Malopolskie, Poland, 30-002
        • Aclaris Investigational Site
    • Mazowieckie
      • Nadarzyn, Mazowieckie, Poland, 05-830
        • Aclaris Investigational Site
    • Mzowieckie
      • Grodzisk Mazowiecki, Mzowieckie, Poland, 05-825
        • Aclaris Investigational Site
    • Podlaskie
      • Białystok, Podlaskie, Poland, 15-351
        • Aclaris Investigational Site
    • Silesia
      • Katowice, Silesia, Poland, 40-282
        • Aclaris Investigational Site
    • Warm.Maz.
      • Elbląg, Warm.Maz., Poland, 82-300
        • Aclaris Investigational Site
    • Warmińsko-Mazurskien
      • Olsztyn, Warmińsko-Mazurskien, Poland, 10-117
        • Aclaris Investigational Site
    • Wielkopolska
      • Poznań, Wielkopolska, Poland, 61-113
        • Aclaris Investigational Site
  • United States
    • California
      • El Cajon, California, United States, 92020
        • Aclaris Investigational Site
      • Encino, California, United States, 91436
        • Aclaris Investigational Site
      • La Jolla, California, United States, 92093
        • Aclaris Investigational Site
      • Palm Desert, California, United States, 92260
        • Aclaris Investigational Site
    • Florida
      • Tampa, Florida, United States, 33613
        • Aclaris Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73103
        • Aclaris Investigational Site
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Aclaris Investigational Site
    • Tennessee
      • Jackson, Tennessee, United States, 38305
        • Aclaris Investigational Site
    • Texas
      • Cypress, Texas, United States, 77429
        • Aclaris Investigational Site
      • Mesquite, Texas, United States, 75150
        • Aclaris Investigational Site
      • San Antonio, Texas, United States, 78229
        • Aclaris Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ATI-450 20 mg BID plus Methotrexate
ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks
Drug: Methotrexate
15 mg to 25 mg weekly
Drug: ATI-450 20 mg oral tablet BID
Oral, small molecule MK2 inhibitor
Other Names:
  • zunsemetinib
Experimental: ATI-450 50 mg BID plus Methotrexate
ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks
Drug: Methotrexate
15 mg to 25 mg weekly
Drug: ATI-450 50 mg oral tablet BID
Oral, small molecule MK2 inhibitor
Other Names:
  • zunsemetinib
Placebo Comparator: Placebo plus Methotrexate
Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks
Drug: Methotrexate
15 mg to 25 mg weekly
Drug: Placebo oral tablet
Placebo tablet manufactured to match ATI-450 in appearance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients achieving ACR20 at Week 12
Time Frame: Baseline to Week 12
Baseline to Week 12

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients achieving ACR50/70 at Week 12
Time Frame: Baseline to Week 12
Baseline to Week 12
Proportion of patients achieving ACR20/50/70 over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Mean change from baseline in DAS28-CRP over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Proportion of patients achieving DAS28-CRP remission (score < 2.6) over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Proportion of patients achieving DAS28-CRP low disease activity (score ≤ 3.2) over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Mean change from baseline in CDAI over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Proportion of patients achieving CDAI remission (score ≤ 2.8) over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Percent change from baseline in hsCRP level over time
Time Frame: Up to 30 days after 12 weeks of treatment
Up to 30 days after 12 weeks of treatment
Health Assessment Questionnaire-Disability Index (HAQ-DI) score over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Short Form Health Survey version-2.0 (SF-36v2) score over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) score over time
Time Frame: Up to 12 Weeks
Up to 12 Weeks
Incidence of adverse events (AEs), serious AEs (SAEs), laboratory value abnormalities, electrocardiogram (ECG) abnormalities, vital signs abnormalities
Time Frame: Baseline to Week 12
Baseline to Week 12
Trough ATI-450 and metabolite (CDD-2164) concentrations at clinic visits (trough and 2-hour post dose will be collected).
Time Frame: Study Days 1, 8, and 85
Study Days 1, 8, and 85

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aclaris Therapeutics, Inc.

Investigators

  • Study Director: Ajay Aggarwal, Aclaris Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2022

Primary Completion (Actual)

September 5, 2023

Study Completion (Actual)

October 11, 2023

Study Registration Dates

First Submitted

February 18, 2022

First Submitted That Met QC Criteria

March 4, 2022

First Posted (Actual)

March 15, 2022

Study Record Updates

Last Update Posted (Estimated)

September 5, 2024

Last Update Submitted That Met QC Criteria

September 3, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATI-450-RA-202
  • 2021-002860-31 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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