Clinical trial NCT05279417: ATI-450 Plus Methotrexate (MTX) Versus Placebo Plus MTX in Participants With Moderate to Severe Active Rheumatoid Arthritis (RA)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid
Arthritis
RA
Lead sponsor: Aclaris Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-15
Enrollment: 251
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients achieving ACR20 at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Proportion of patients achieving ACR50/70 at Week 12
timeFrame: Baseline to Week 12
measure: Proportion of patients achieving ACR20/50/70 over time
timeFrame: Up to 12 Weeks
measure: Mean change from baseline in DAS28-CRP over time
timeFrame: Up to 12 Weeks
measure: Proportion of patients achieving DAS28-CRP remission (score < 2.6) over time
timeFrame: Up to 12 Weeks
measure: Proportion of patients achieving DAS28-CRP low disease activity (score ≤ 3.2) over time
timeFrame: Up to 12 Weeks
measure: Mean change from baseline in CDAI over time
timeFrame: Up to 12 Weeks
measure: Proportion of patients achieving CDAI remission (score ≤ 2.8) over time
timeFrame: Up to 12 Weeks
measure: Percent change from baseline in hsCRP level over time
timeFrame: Up to 30 days after 12 weeks of treatment
measure: Health Assessment Questionnaire-Disability Index (HAQ-DI) score over time
timeFrame: Up to 12 Weeks
measure: Short Form Health Survey version-2.0 (SF-36v2) score over time
timeFrame: Up to 12 Weeks
measure: Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) score over time
timeFrame: Up to 12 Weeks
measure: Incidence of adverse events (AEs), serious AEs (SAEs), laboratory value abnormalities, electrocardiogram (ECG) abnormalities, vital signs abnormalities
timeFrame: Baseline to Week 12
measure: Trough ATI-450 and metabolite (CDD-2164) concentrations at clinic visits (trough and 2-hour post dose will be collected).
timeFrame: Study Days 1, 8, and 85
Other outcomes:
Locations:
city: El Cajon
country: United States
facility: Aclaris Investigational Site
state: California
city: Encino
country: United States
facility: Aclaris Investigational Site
state: California
city: La Jolla
country: United States
facility: Aclaris Investigational Site
state: California
city: Palm Desert
country: United States
facility: Aclaris Investigational Site
state: California
city: Tampa
country: United States
facility: Aclaris Investigational Site
state: Florida
city: Oklahoma City
country: United States
facility: Aclaris Investigational Site
state: Oklahoma
city: Duncansville
country: United States
facility: Aclaris Investigational Site
state: Pennsylvania
city: Jackson
country: United States
facility: Aclaris Investigational Site
state: Tennessee
city: Cypress
country: United States
facility: Aclaris Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Aclaris Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Aclaris Investigational Site
state: Texas
city: Pleven
country: Bulgaria
facility: Aclaris Investigational Site
city: Plovdiv
country: Bulgaria
facility: Aclaris Investigational Site
city: Plovdiv
country: Bulgaria
facility: Aclaris Investigational Site
city: Plovdiv
country: Bulgaria
facility: Aclaris Investigational Site
city: Plovdiv
country: Bulgaria
facility: Aclaris Investigational Site
city: Sofia
country: Bulgaria
facility: Aclaris Investigational Site
city: Sofia
country: Bulgaria
facility: Aclaris Investigational Site
city: Sofia
country: Bulgaria
facility: Aclaris Investigational Site
city: Varna
country: Bulgaria
facility: Aclaris Investigational Site
city: Brno
country: Czechia
facility: Aclaris Investigational Site
city: Hlučín
country: Czechia
facility: Aclaris Investigational Site
city: Ostrava
country: Czechia
facility: Aclaris Investigational Site
city: Pardubice
country: Czechia
facility: Aclaris Investigational Site
city: Praha
country: Czechia
facility: Aclaris Investigational Site
city: Praha
country: Czechia
facility: Aclaris Investigational Site
city: Uherské Hradiště
country: Czechia
facility: Aclaris Investigational Site
city: Lublin
country: Poland
facility: Aclaris Investigational Site
state: Lubelskie
city: Tomaszów Lubelski
country: Poland
facility: Aclaris Investigational Site
state: Lubelski
city: Kraków
country: Poland
facility: Aclaris Investigational Site
state: Malopolskie
city: Nadarzyn
country: Poland
facility: Aclaris Investigational Site
state: Mazowieckie
city: Grodzisk Mazowiecki
country: Poland
facility: Aclaris Investigational Site
state: Mzowieckie
city: Białystok
country: Poland
facility: Aclaris Investigational Site
state: Podlaskie
city: Katowice
country: Poland
facility: Aclaris Investigational Site
state: Silesia
city: Elbląg
country: Poland
facility: Aclaris Investigational Site
state: Warm.Maz.
city: Olsztyn
country: Poland
facility: Aclaris Investigational Site
state: Warmińsko-Mazurskien
city: Poznań
country: Poland
facility: Aclaris Investigational Site
state: Wielkopolska
city: Białystok
country: Poland
facility: Aclaris Investigational Site
city: Białystok
country: Poland
facility: Aclaris Investigational Site
city: Dąbrówka
country: Poland
facility: Aclaris Investigational Site
city: Kraków
country: Poland
facility: Aclaris Investigational Site
city: Lublin
country: Poland
facility: Aclaris Investigational Site
city: Nowa Sól
country: Poland
facility: Aclaris Investigational Site
city: Poznań
country: Poland
facility: Aclaris Investigational Site
city: Poznań
country: Poland
facility: Aclaris Investigational Site
city: Poznań
country: Poland
facility: Aclaris Investigational Site
city: Sochaczew
country: Poland
facility: Aclaris Investigational Site
city: Toruń
country: Poland
facility: Aclaris Investigational Site
city: Warszawa
country: Poland
facility: Aclaris Investigational Site
city: Wrocław
country: Poland
facility: Aclaris Investigational Site
Study officials:
affiliation: Aclaris Therapeutics, Inc.
name: Ajay Aggarwal
role: STUDY_DIRECTOR
References: