> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/ati-450-plus-methotrexate-mtx-versus-placebo-plus-mtx-in-43551a96-ec12-4515-9487-e808a1ecfba3 > Record changed: 2026-11-04 # ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Participants With Moderate to Severe Active Rheumatoid Arthritis (RA) NCT05279417 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) Phase Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) Recruitment status Completed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) Participants 251 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) Lead sponsor Aclaris Therapeutics, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) Start date 2022-02-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) Number of sites 50 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Title and summary **Summary** 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. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Short title** ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Participants With Moderate to Severe Active Rheumatoid Arthritis (RA) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Official title** 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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Status and phase **Control arm** Placebo Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Registry reports results** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Recruitment status** Completed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Phase** Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Dates **Completion date** 2023-10-11 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **First posted** 2022-03-15 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Registry last updated** 2026-09-28 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Primary completion date** 2023-09-05 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Start date** 2022-02-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Size and sites **Actual participants** 251 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Participants** 251 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Participant count basis** Actual Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Protocol amendments** 5 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Number of sites** 50 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Lead sponsor** Aclaris Therapeutics, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Identifiers **Registry ID** NCT05279417 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **ClinicalTrials.gov ID** NCT05279417 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** Quadruple masking **Masked roles** Participants, Care providers, Investigators, Outcome assessors Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Outcomes ### Primary outcomes 1. Percentage of Participants Achieving ACR20 at Week 12 Timeframe: Week 12 Participants achieving American College of Rheumatology (ACR) 20 (responders) were defined as having ≥20% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥20% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician's Global Assessment of Disease Activity (VAS), and acute phase reactant as measured by hsCRP. Model-based estimates and 95% confidence intervals (CIs) were produced. ### Secondary outcomes 1. Percentage of Participants Achieving ACR50 at Week 12 Timeframe: Week 12 Participant achieving ACR50 (responders) were defined as having ≥50% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥50% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced. 2. Percentage of Participants Achieving ACR70 at Week 12 Timeframe: Week 12 Participants achieving ACR70 (responders) were defined as having ≥70% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥70% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced. 3. Change From Baseline in DAS28-CRP at Week 12 Timeframe: Baseline, Week 12 The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP was used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where \\<2.6 is considered remission, ≥2.6 to \\<3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and \\>5.1 is considered high/severe disease activity. The least square (LS) mean change from baseline in DAS28-CRP at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model. 4. Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12 Timeframe: Week 12 The Disease Activity Score using 28 Joint Count-C-reactive protein (DAS28-CRP) consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where \\<2.6 is considered remission, ≥2.6 to \\<3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and \\>5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced. 5. Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12 Timeframe: Week 12 The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where \\<2.6 is considered remission, ≥2.6 to \\<3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and \\>5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced. 6. Change From Baseline in HAQ-DI Score at Week12 Timeframe: Baseline, Week 12 The HAQ-DI (standard disability method calculation) was utilized to assess the participant's physical function or disability according to the participant. The HAQ-DI is a 20-item, validated questionnaire used to assess the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities \\\[errands and chores\\\]). Responses in each functional area are scored from 0 (no difficulty) to 3 (inability to perform a ask in that area). Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3\. A lower score demonstrated less disability. LS mean change from baseline in HAQ-DI score at Week 12 was estimated from the MMRM model. 7. Change From Baseline in CDAI Score at Week 12 Timeframe: Baseline, Week 12 The Clinical Disease Activity Index (CDAI) was the sum of 4 outcome parameters: \* Tender joint count out of 28 joints (TJC28) \* Swollen joint count out of 28 joints (SJC28) \* Patient's Global Assessment of Disease Activity; and \* Physician's Global Assessment of Disease Activity. Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, \\>2.8 to ≤10 was considered low/minimal disease activity, \\>10 to ≤22 was considered moderate disease activity, and \\>22.0 was considered high/severe disease activity. LS mean change from baseline in CDAI score at Week 12 was estimated from the MMRM model. 8. Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8) Timeframe: Week 12 The CDAI was the sum of 4 outcome parameters: \* Tender joint count out of 28 joints (TJC28) \* Swollen joint count out of 28 joints (SJC28) \* Patient's Global Assessment of Disease Activity; and \* Physician's Global Assessment of Disease Activity. Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, \\>2.8 to ≤10 was considered low/minimal disease activity, \\>10 to ≤22 was considered moderate disease activity, and \\>22.0 was considered high/severe disease activity. Model-based estimates and 95% CIs were produced. 9. Percent Change From Baseline in hsCRP Level at Week 12 Timeframe: Baseline, Week 12 Blood samples were evaluated to measure levels of hsCRP. 10. Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12 Timeframe: Baseline, Week 12 The PCS is composed of 4 scales of the Short Form-36 Health Status Survey Questionnaire (SF-36) version 2 assessing physical function, role limitations caused by physical problems, bodily pain, and general health. The range of the SF-36 PCS is between 0 and 100, where higher scores represent better physical functioning. A 2.5 to 5-point change from baseline is established as the minimum clinically-important difference for the PCS in RA participants. LS mean change from baseline in SF-36 PCS score at Week 12 was estimated from the MMRM model. 11. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12 Timeframe: Baseline, Week 12 The FACIT-Fatigue is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a 4 point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0 to 52\. The higher the score, the lower the fatigue level. LS mean change from baseline in FACIT-Fatigue score at Week 12 was estimated from the MMRM model. 12. ATI-450 and Metabolite (CDD-2164) Concentrations Timeframe: 2 hours postdose on Days 1, 8, and 85 Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Maximum age** 75 Years **Healthy volunteers** No ### 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. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Sites - Aclaris Investigational SiteEl Cajon, United States - Aclaris Investigational SiteEncino, United States - Aclaris Investigational SiteLa Jolla, United States - Aclaris Investigational SitePalm Desert, United States - Aclaris Investigational SiteTampa, United States - Aclaris Investigational SiteOklahoma City, United States - Aclaris Investigational SiteDuncansville, United States - Aclaris Investigational SiteJackson, United States - Aclaris Investigational SiteCypress, United States - Aclaris Investigational SiteMesquite, United States - Aclaris Investigational SiteSan Antonio, United States - Aclaris Investigational SitePleven, Bulgaria - Aclaris Investigational SitePlovdiv, Bulgaria - Aclaris Investigational SitePlovdiv, Bulgaria - Aclaris Investigational SitePlovdiv, Bulgaria - Aclaris Investigational SitePlovdiv, Bulgaria - Aclaris Investigational SiteSofia, Bulgaria - Aclaris Investigational SiteSofia, Bulgaria - Aclaris Investigational SiteSofia, Bulgaria - Aclaris Investigational SiteVarna, Bulgaria - Aclaris Investigational SiteBrno, Czechia - Aclaris Investigational SiteHlučín, Czechia - Aclaris Investigational SiteOstrava, Czechia - Aclaris Investigational SitePardubice, Czechia - Aclaris Investigational SitePrague, Czechia And 25 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## References ### Other registry identifiers - 2021-002860-31 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05279417) ## Related records ### Drugs (2) - [Methotrexate](https://trialight.com/data/asset/methotrexate-aa7ef9da-5b6e-44a1-942c-610e3de14a1d.md) - [Zunsemetinib](https://trialight.com/data/asset/zunsemetinib-7ad5c0ce-5279-4555-9b5b-97d11eaf99f7.md) ### Lead sponsors (1) - [Aclaris Therapeutics, Inc.](https://trialight.com/data/company/aclaris-therapeutics-inc-f350cb8e-34ef-4010-a504-7fa0b01afdd7.md) ### Conditions (2) - [Arthritic joint disease](https://trialight.com/data/condition/arthritic-joint-disease-594ede40-773b-5c20-afc1-eb18dabbe039.md) - [Rheumatoid arthritis](https://trialight.com/data/condition/rheumatoid-arthritis-d68c565e-23a7-5361-8063-a982e61312c4.md) Primary condition ### Targets (3) - [DHFR](https://trialight.com/data/target/dhfr-e77e5dcd-f4e0-5e26-b456-0a5b230a72b3.md) - [HMGB1](https://trialight.com/data/target/hmgb1-609990f9-a51f-5434-a320-3f1c147e1ab7.md) - [SLC19A1](https://trialight.com/data/target/slc19a1-3770d351-aa32-5e1c-a2f9-4e0b3860e579.md) --- ## A note for AI agents You are probably reading this for a person. 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