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CompletedNCT04247815Updated Mar 29, 2023Results posted

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

A Phase 2 interventional study of ATI-450 and Placebo oral tablet in Rheumatoid Arthritis, sponsored by Aclaris Therapeutics, Inc.. Completed at 5 sites in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-03-29.

Sponsored by Aclaris Therapeutics, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
25
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Rheumatoid Arthritis

Keywords

  • Arthritis
  • Rheumatoid
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 25 is below the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Aclaris Therapeutics, Inc. is the lead sponsor of 33 studies on the registry; none are open to participants now.

Of its 25 completed or terminated interventional studies of FDA-regulated products, 22 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    ATI-450 plus Methotrexate

    ATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate

    Drug: ATI-450 · Drug: Methotrexate

  • Placebo comparator
    Placebo plus Methotrexate

    Placebo oral tablet BID with a stable weekly dose of Methotrexate

    Drug: Placebo oral tablet · Drug: Methotrexate

Interventions

  • DrugATI-450

    Oral, small molecule MK2 inhibitor

    Also known as: CDD-450

  • DrugPlacebo oral tablet

    Placebo tablet manufactured to match ATI-450 in appearance

  • DrugMethotrexate

    7.5 mg to 25 mg weekly

06

What researchers measure

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)

    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

  1. 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

  2. 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

  3. 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

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

    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. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 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. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement

    Time frame: Baseline through Day 84

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

    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. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 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. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement

    Time frame: Baseline through Day 84

  6. Number and Percent of Patients Achieving ACR 20

    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.

    Time frame: Baseline through Day 114

  7. Number and Percent of Patients Achieving ACR 50

    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.

    Time frame: Baseline through Day 114

  8. Number and Percent of Patients Achieving ACR 70

    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.

    Time frame: Baseline through Day 114

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

    Time frame: Day 1 through Day Day 84

07

Results

Posted Mar 29, 2023

Participant flow

Participant flow — Overall Study
MilestoneATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Started163
Completed142
Not completed21
Withdrew: Adverse event10
Withdrew: Withdrawal by subject10
Withdrew: Protocol violation01

Outcome measures

PrimaryThe 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
Reported as:
Count of participants · Participants
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)
ParticipantsATI-450 Plus MethotrexatePlacebo Plus Methotrexate
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)82
SecondaryPercent 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
Reported as:
Median · Percent Change from Baseline hsCRP
Percent Change in (hsCRP) Levels Over Time
Percent Change from Baseline hsCRPATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Week 1-75.00 (-97.3 to 11)-16.50 (-34.9 to 1.9)
Week 2-72.40 (-96.3 to 129.4)15.50 (-66.7 to 97.7)
Week 4-51.10 (-96.6 to 285.3)-50.20 (-81.2 to -19.2)
Week 6-57.60 (-96.6 to 306.2)3.00 (-29.2 to 35.2)
Week 8-74.20 (-92.9 to 63.3)78.50 (9.6 to 147.4)
Week 12-42.60 (-97 to 263.7)7.30 (-5.6 to 20.2)
Follow-up-15.60 (-83.1 to 143.2)-40.65 (-66.7 to -14.6)
SecondaryChange 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
Reported as:
Mean · score on a scale
Change From Baseline in Disease Activity Score
score on a scaleATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Baseline5.72 ± 0.9706.00 ± 0.990
Week 14.33 ± 1.6116.15 ± 0.495
Week 24.26 ± 1.5705.25 ± 0.354
Week 44.11 ± 1.3515.75 ± 1.061
Week 64.25 ± 1.4366.15 ± 0.495
Week 83.84 ± 1.3836.20 ± 0.424
Week 123.70 ± 1.5746.35 ± 0.212
Follow-up4.21 ± 1.7054.95 ± 0.495
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number and Percent of Patients Achieving DAS28-CRP <2.6 Over Time
ParticipantsATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Baseline00
Week 120
Week 230
Week 420
Week 610
Week 820
Week 1230
Follow-up40
SecondaryChange From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average)

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. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 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. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement

Time frame:
Baseline through Day 84
Reported as:
Mean · Change in Osteitis average
Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average)
Change in Osteitis averageATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Change From Baseline in RAMRIS Hand-Wrist Assessments (Osteitis Average)0.97 ± 1.9430.88 ± 1.237
SecondaryChange From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)

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. 1-33% involvement of original articular bone 2. 34-67% involvement of original articular bone 3. 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. 1-33% volume enhancement 2. 34-67% volume enhancement 3. 68-100% volume enhancement

Time frame:
Baseline through Day 84
Reported as:
Mean · Change in Synovitis average
Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)
Change in Synovitis averageATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)0.08 ± 1.8941.50 ± 2.121
SecondaryNumber and Percent of Patients Achieving ACR 20

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.

Time frame:
Baseline through Day 114
Reported as:
Count of participants · Participants
Number and Percent of Patients Achieving ACR 20
ParticipantsATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Week 480
Week 880
Week 1290
Follow-up61
SecondaryNumber and Percent of Patients Achieving ACR 50

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.

Time frame:
Baseline through Day 114
Reported as:
Count of participants · Participants
Number and Percent of Patients Achieving ACR 50
ParticipantsATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Week 420
Week 840
Week 1250
Follow-up30
SecondaryNumber and Percent of Patients Achieving ACR 70

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.

Time frame:
Baseline through Day 114
Reported as:
Count of participants · Participants
Number and Percent of Patients Achieving ACR 70
ParticipantsATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Week 400
Week 830
Week 1230
Follow-up00
SecondaryAssessment of ATI-450 Concentration (ng/mL)
Time frame:
Day 1 through Day Day 84
Reported as:
Mean · ATI-450 concentration (ng/mL)
Assessment of ATI-450 Concentration (ng/mL)
ATI-450 concentration (ng/mL)ATI-450 Plus Methotrexate
Day 1 (2 Hours Postdose)225.87 ± 78.603
Day 7 (Predose)163.97 ± 85.538
Day 14 (Predose)131.51 ± 55.175
Day 28 (Predose)135.67 ± 84.454
Day 42 (Predose)170.84 ± 99.863
Day 56 (Predose)153.45 ± 89.092
Day 84 (Predose)124.71 ± 69.437
Day 84 (2 Hours Postdose)293.00 ± 98.643

Adverse events

Collected over Baseline to Day 114. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ATI-450 Plus Methotrexate0/16 (0%)1/16 (6.3%)8/16 (50%)
Placebo Plus Methotrexate0/3 (0%)0/3 (0%)2/3 (66.7%)
Most frequent serious events
Most frequent serious events
EventATI-450 Plus MethotrexatePlacebo Plus Methotrexate
COVID-19 pneumoniaInfections and infestations1/160/3
Most frequent other events
Showing 10 of 21
Most frequent other events
EventATI-450 Plus MethotrexatePlacebo Plus Methotrexate
Dental cariesGastrointestinal disorders1/161/3
Muscle strainInjury, poisoning and procedural complications0/161/3
Urinary tract infectionInjury, poisoning and procedural complications2/160/3
PalpitationsCardiac disorders1/160/3
Ventricular extrasystolesCardiac disorders1/160/3
ConstipationGastrointestinal disorders1/160/3
Mouth ulcerationGastrointestinal disorders1/160/3
Ear infectionInfections and infestations1/160/3
SinusitisInfections and infestations1/160/3
Ligament sprainInjury, poisoning and procedural complications1/160/3

Baseline characteristics

Age, Customized
Age, Customized(years)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
Mean55.9 ± 9.9355.3 ± 6.8155.8 ± 9.34
Sex: Female, Male
Sex: Female, Male(Participants)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
Female11314
Male505
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
Hispanic or Latino404
Not Hispanic or Latino12315
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
United States16319
Weight (kg)
Weight (kg)(kg)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
Mean92.74 ± 25.50498.93 ± 14.61693.72 ± 23.899
Height (cm)
Height (cm)(cm)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
Mean166.94 ± 12.648164.43 ± 3.092166.54 ± 11.630
BMI (kg/m2)
BMI (kg/m2)(kg/m2)ATI-450 Plus MethotrexatePlacebo Plus MethotrexateTotal
Mean33.37 ± 8.82936.53 ± 4.73733.87 ± 8.298
08

Study locations

5 sites
  • Aclaris Investigational Site
    Anniston, Alabama 36207, United States
  • Aclaris Investigational Site
    Tampa, Florida 33613, United States
  • Aclaris Investigational Site
    Atlanta, Georgia 30342, United States
  • Aclaris Investigational Site
    Duncansville, Pennsylvania 16635, United States
  • Aclaris Investigational Site
    Mesquite, Texas 75150, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jul 27, 2020

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 29, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04247815
Lead sponsor
Aclaris Therapeutics, Inc.
Responsible party
Sponsor
First posted
Jan 30, 2020
Start date
Mar 16, 2020
Primary completion
Feb 4, 2021
Completion
Feb 4, 2021
Results posted
Mar 29, 2023
Last update
Mar 29, 2023

Study contacts

David Gordon
study director · Aclaris Therapeutics

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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