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ATI-450 Plus MTX versus Placebo Plus MTX hos pasienter med moderat til alvorlig aktiv RA

2. september 2026 oppdatert av: Aclaris Therapeutics, Inc.

ATI-450 Plus MTX versus Placebo Plus MTX hos pasienter med moderat til alvorlig aktiv RA som har hatt en utilstrekkelig respons på MTX alene

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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

251

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4000
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4001
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4002
        • Aclaris Investigational Site
      • Plovdiv, Bulgaria, 4004
        • Aclaris Investigational Site
      • Sofia, Bulgaria, 1336
        • Aclaris Investigational Site
      • Sofia, Bulgaria, 1431
        • Aclaris Investigational Site
      • Sofia, Bulgaria, 1606
        • Aclaris Investigational Site
      • Varna, Bulgaria, 9000
        • Aclaris Investigational Site
  • Forente stater
    • California
      • El Cajon, California, Forente stater, 92020
        • Aclaris Investigational Site
      • Encino, California, Forente stater, 91436
        • Aclaris Investigational Site
      • La Jolla, California, Forente stater, 92093
        • Aclaris Investigational Site
      • Palm Desert, California, Forente stater, 92260
        • Aclaris Investigational Site
    • Florida
      • Tampa, Florida, Forente stater, 33613
        • Aclaris Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, Forente stater, 73103
        • Aclaris Investigational Site
    • Pennsylvania
      • Duncansville, Pennsylvania, Forente stater, 16635
        • Aclaris Investigational Site
    • Tennessee
      • Jackson, Tennessee, Forente stater, 38305
        • Aclaris Investigational Site
    • Texas
      • Cypress, Texas, Forente stater, 77429
        • Aclaris Investigational Site
      • Mesquite, Texas, Forente stater, 75150
        • Aclaris Investigational Site
      • San Antonio, Texas, Forente stater, 78229
        • Aclaris Investigational Site
  • Polen
      • Bialystok, Polen, 15-297
        • Aclaris Investigational Site
      • Bialystok, Polen, 15-879
        • Aclaris Investigational Site
      • Dąbrówka, Polen, 62-069
        • Aclaris Investigational Site
      • Krakow, Polen, 30-363
        • Aclaris Investigational Site
      • Lublin, Polen, 20-607
        • Aclaris Investigational Site
      • Nowa Sól, Polen, 67-100
        • Aclaris Investigational Site
      • Poznan, Polen, 60-218
        • Aclaris Investigational Site
      • Poznan, Polen, 60-446
        • Aclaris Investigational Site
      • Poznan, Polen, 61-397
        • Aclaris Investigational Site
      • Sochaczew, Polen, 96-500
        • Aclaris Investigational Site
      • Torun, Polen, 87-100
        • Aclaris Investigational Site
      • Warsaw, Polen, 04-141
        • Aclaris Investigational Site
      • Wroclaw, Polen, 52-442
        • Aclaris Investigational Site
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Polen, 30-002
        • Aclaris Investigational Site
    • Lubelski
      • Tomaszów Lubelski, Lubelski, Polen, 22-600
        • Aclaris Investigational Site
    • Lublin Voivodeship
      • Lublin, Lublin Voivodeship, Polen, 20-362
        • Aclaris Investigational Site
    • Masovian Voivodeship
      • Nadarzyn, Masovian Voivodeship, Polen, 05-830
        • Aclaris Investigational Site
    • Mzowieckie
      • Grodzisk Mazowiecki, Mzowieckie, Polen, 05-825
        • Aclaris Investigational Site
    • Podlaskie Voivodeship
      • Bialystok, Podlaskie Voivodeship, Polen, 15-351
        • Aclaris Investigational Site
    • Silesian Voivodeship
      • Katowice, Silesian Voivodeship, Polen, 40-282
        • Aclaris Investigational Site
    • Warm.Maz.
      • Elblag, Warm.Maz., Polen, 82-300
        • Aclaris Investigational Site
    • Warmińsko-Mazurskien
      • Olsztyn, Warmińsko-Mazurskien, Polen, 10-117
        • Aclaris Investigational Site
    • Wielkopolska
      • Poznan, Wielkopolska, Polen, 61-113
        • Aclaris Investigational Site
  • Tsjekkia
      • Brno, Tsjekkia, 615 00
        • Aclaris Investigational Site
      • Hlučín, Tsjekkia, 748 01
        • Aclaris Investigational Site
      • Ostrava, Tsjekkia, 702 00
        • Aclaris Investigational Site
      • Pardubice, Tsjekkia, 530 02
        • Aclaris Investigational Site
      • Prague, Tsjekkia, 128 50
        • Aclaris Investigational Site
      • Prague, Tsjekkia, 140 00
        • Aclaris Investigational Site
      • Uherské Hradiště, Tsjekkia, 686 01
        • Aclaris Investigational Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 75 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: ATI-450 20 mg BID plus Methotrexate

ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks
Legemiddel: Methotrexate

15 mg to 25 mg weekly

Legemiddel: ATI-450 20 mg oral tablet BID

Oral, small molecule MK2 inhibitor

Andre navn:
  • zunsemetinib
Eksperimentell: ATI-450 50 mg BID plus Methotrexate

ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks
Legemiddel: Methotrexate

15 mg to 25 mg weekly

Legemiddel: ATI-450 50 mg oral tablet BID

Oral, small molecule MK2 inhibitor

Andre navn:
  • zunsemetinib
Placebo komparator: Placebo plus Methotrexate

Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks
Legemiddel: Methotrexate

15 mg to 25 mg weekly

Legemiddel: Placebo oral tablet

Placebo tablet manufactured to match ATI-450 in appearance

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants Achieving ACR20 at Week 12
Tidsramme: 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.
Week 12

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
ATI-450 og metabolitt (CDD-2164)-konsentrasjoner
Tidsramme: 2 timer etter dosering på dag 1, 8 og 85
2 timer etter dosering på dag 1, 8 og 85
Percentage of Participants Achieving ACR50 at Week 12
Tidsramme: 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.
Week 12
Percentage of Participants Achieving ACR70 at Week 12
Tidsramme: 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.
Week 12
Change From Baseline in DAS28-CRP at Week 12
Tidsramme: 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.
Baseline, Week 12
Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12
Tidsramme: 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.
Week 12
Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12
Tidsramme: 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.
Week 12
Change From Baseline in HAQ-DI Score at Week12
Tidsramme: 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.
Baseline, Week 12
Change From Baseline in CDAI Score at Week 12
Tidsramme: 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.
Baseline, Week 12
Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)
Tidsramme: 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.
Week 12
Percent Change From Baseline in hsCRP Level at Week 12
Tidsramme: Baseline, Week 12

Blood samples were evaluated to measure levels of hsCRP.
Baseline, Week 12
Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12
Tidsramme: 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.
Baseline, Week 12
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12
Tidsramme: 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.
Baseline, Week 12

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Aclaris Therapeutics, Inc.

Etterforskere

  • Studieleder: Ajay Aggarwal, Aclaris Therapeutics, Inc.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

1. februar 2022

Primær fullføring (Faktiske)

5. september 2023

Studiet fullført (Faktiske)

11. oktober 2023

Datoer for studieregistrering

Først innsendt

18. februar 2022

Først innsendt som oppfylte QC-kriteriene

4. mars 2022

Først lagt ut (Faktiske)

15. mars 2022

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

28. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

2. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • ATI-450-RA-202
  • 2021-002860-31 (EudraCT-nummer)

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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