Rheumatoid ArthritisPhase 2NCT04247815

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

A Phase 2 study testing ATI-450 and Methotrexate in people with Rheumatoid Arthritis, run by Aclaris Therapeutics, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: ATI-450 and Methotrexate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 25 participants
Where: 5 sitesUnited States
Study dates: 16 Mar 2020to 4 Feb 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Aclaris Investigational Site
Anniston, Alabama, 36207
Aclaris Investigational Site
Atlanta, Georgia, 30342
Aclaris Investigational Site
Duncansville, Pennsylvania, 16635
Aclaris Investigational Site
Mesquite, Texas, 75150
Aclaris Investigational Site
Tampa, Florida, 33613

Other trials in United States

About this study

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

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.

Conditions: Rheumatoid Arthritis
Being tested: ATI-450, Placebo oral tablet, Methotrexate
Keywords: Arthritis, Rheumatoid
Medical subject headings: Arthritis, Rheumatoid, Arthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ATI-450Drug
Also called CDD-450
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

Study groups in NCT04247815
Study group	Role	What they receive
ATI-450 plus Methotrexate	Experimental	ATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate Receives: Drug: ATI-450; Drug: Methotrexate
Placebo plus Methotrexate	Placebo comparator	Placebo oral tablet BID with a stable weekly dose of Methotrexate Receives: Drug: Placebo oral tablet; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline through Day 114

Secondary outcomes (9)

Percent Change in (hsCRP) Levels Over Time
Median percent change from baseline in high sensitivity C-reactive protein (hsCRP) levels over time
Measured: 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.
Measured: 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
Measured: Baseline through Day 114
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
Measured: Baseline through Day 84
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
Measured: Baseline through Day 84
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.
Measured: Baseline through Day 114
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.
Measured: Baseline through Day 114
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.
Measured: Baseline through Day 114
Assessment of ATI-450 Concentration (ng/mL)
Measured: Day 1 through Day Day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Mar 20204 Feb 2021

First posted30 Jan 2020
Study start16 Mar 2020
Primary completion4 Feb 2021
Study completion4 Feb 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, investigator and patient-blind, sponsor-unblinded, parallel group.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04247815
Sponsor's protocol ID: ATI-450-RA-201
Status last verified: Mar 2023
First submitted: 16 Jan 2020
Last updated: 29 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04247815
Acronym / sponsor ID: ATI-450-RA-201
Conditions: Rheumatoid Arthritis
Keywords: Arthritis, Rheumatoid
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Aclaris Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 16 Mar 2020 (actual)
Primary completion: 4 Feb 2021 (actual)
Study completion: 4 Feb 2021 (actual)
First posted: 30 Jan 2020 (actual)
Results: Posted 29 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Randomized, investigator and patient-blind, sponsor-unblinded, parallel group.

Arm	Type	Receives
ATI-450 plus Methotrexate	Experimental	Drug: ATI-450, Drug: MethotrexateATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate
Placebo plus Methotrexate	Placebo comparator	Drug: Placebo oral tablet, Drug: MethotrexatePlacebo oral tablet BID with a stable weekly dose of Methotrexate

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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).

Key exclusion criteria (9 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ATI-450Also: CDD-450Oral, small molecule MK2 inhibitor	Drug	ATI-450 plus Methotrexate
Placebo oral tabletPlacebo tablet manufactured to match ATI-450 in appearance	Drug	Placebo plus Methotrexate
Methotrexate7.5 mg to 25 mg weekly	Drug	ATI-450 plus Methotrexate, Placebo plus Methotrexate

Primary outcome

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.

9 secondary outcomes

Percent Change in (hsCRP) Levels Over Time
Time frame: Baseline through Day 114
Change From Baseline in Disease Activity Score
Time frame: Baseline through Day 114
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)
Time frame: Baseline through Day 84
Change From Baseline in RAMRIS Hand-Wrist Assessments (Synovitis Average)
Time frame: Baseline through Day 84
Number and Percent of Patients Achieving ACR 20
Time frame: Baseline through Day 114
Number and Percent of Patients Achieving ACR 50
Time frame: Baseline through Day 114
Number and Percent of Patients Achieving ACR 70
Time frame: Baseline through Day 114
Assessment of ATI-450 Concentration (ng/mL)
Time frame: Day 1 through Day Day 84

Results and safety

Results posted to the registry on 29 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ATI-450 Plus Methotrexate	16	14
Placebo Plus Methotrexate	3	2

Primary outcome: 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. Count of participants. Unit: Participants

Measure	ATI-450 Plus Methotrexate n = 16	Placebo Plus Methotrexate n = 3
Value	8	2

Population analysed: The Safety population consisted of patients who receive at least 1 dose of study drug. This set was used for the safety data summaries and baseline characteristic summaries. This set was analyzed as treated.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to Day 114. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ATI-450 Plus Methotrexate	1 of 16 (6.3%)	8 of 16 (50%)	0 of 16
Placebo Plus Methotrexate	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Gordon study director

Aclaris Therapeutics

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ATI-450 and Methotrexate in people with Rheumatoid Arthritis, run by Aclaris Therapeutics, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04247815.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.