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

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

ATI-450

Placebo oral tablet

Methotrexate

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Arthritis, Rheumatoid

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Aclaris Investigational Site
Aclaris Investigational Site
Aclaris Investigational Site
Aclaris Investigational Site
Aclaris Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ATI-450 plus Methotrexate

Placebo plus Methotrexate

Arm Description

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

Placebo oral tablet BID with a stable weekly dose of Methotrexate

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percent Change in (hsCRP) Levels Over Time

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

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.

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

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

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 1-33% 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

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

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.

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.

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.

Assessment of ATI-450 Concentration (ng/mL)

Full Information

NCT ID

NCT04247815

First Posted

January 16, 2020

Last Updated

March 3, 2023

Sponsor

Aclaris Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04247815

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

March 16, 2020 (Actual)

Primary Completion Date

February 4, 2021 (Actual)

Study Completion Date

February 4, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aclaris Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Arthritis, Rheumatoid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Randomized, investigator and patient-blind, sponsor-unblinded, parallel group.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

The blinded placebo drug is packaged to match the active study drug and will be stored under the same conditions.

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ATI-450 plus Methotrexate

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo plus Methotrexate

Arm Type

Placebo Comparator

Arm Description

Placebo oral tablet BID with a stable weekly dose of Methotrexate

Intervention Type

Drug

Intervention Name(s)

ATI-450

Other Intervention Name(s)

CDD-450

Intervention Description

Oral, small molecule MK2 inhibitor

Intervention Type

Drug

Intervention Name(s)

Placebo oral tablet

Intervention Description

Placebo tablet manufactured to match ATI-450 in appearance

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Description

7.5 mg to 25 mg weekly

Primary Outcome Measure Information:

Title

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)

Description

Time Frame

Baseline through Day 114

Secondary Outcome Measure Information:

Title

Percent Change in (hsCRP) Levels Over Time

Description

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

Time Frame

Baseline through Day 114

Title

Change From Baseline in Disease Activity Score

Description

Time Frame

Baseline through Day 114

Title

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

Description

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

Time Frame

Baseline through Day 114

Title

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

Description

Time Frame

Baseline through Day 84

Title

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

Description

Time Frame

Baseline through Day 84

Title

Number and Percent of Patients Achieving ACR 20

Description

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

Title

Number and Percent of Patients Achieving ACR 50

Description

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

Title

Number and Percent of Patients Achieving ACR 70

Description

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

Title

Assessment of ATI-450 Concentration (ng/mL)

Time Frame

Day 1 through Day Day 84

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Gordon

Organizational Affiliation

Aclaris Therapeutics

Official's Role

Study Director

Facility Information:

Facility Name

Aclaris Investigational Site

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36207

Country

United States

Facility Name

Aclaris Investigational Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

Aclaris Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Aclaris Investigational Site

City

Duncansville

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Facility Name

Aclaris Investigational Site

City

Mesquite

State/Province

Texas

ZIP/Postal Code

75150

Country

United States

12. IPD Sharing Statement

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

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