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ATI-450 Plus MTX versus Placebo Plus MTX hos patienter med moderat til svær aktiv RA

2. september 2026 opdateret af: Aclaris Therapeutics, Inc.

ATI-450 Plus MTX versus Placebo Plus MTX hos patienter med moderat til svær aktiv RA, som har haft en utilstrækkelig 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret 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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

251

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Bulgarien
      • Pleven, Bulgarien, 5800
        • Aclaris Investigational Site
      • Plovdiv, Bulgarien, 4000
        • Aclaris Investigational Site
      • Plovdiv, Bulgarien, 4001
        • Aclaris Investigational Site
      • Plovdiv, Bulgarien, 4002
        • Aclaris Investigational Site
      • Plovdiv, Bulgarien, 4004
        • Aclaris Investigational Site
      • Sofia, Bulgarien, 1336
        • Aclaris Investigational Site
      • Sofia, Bulgarien, 1431
        • Aclaris Investigational Site
      • Sofia, Bulgarien, 1606
        • Aclaris Investigational Site
      • Varna, Bulgarien, 9000
        • Aclaris Investigational Site
  • Forenede Stater
    • California
      • El Cajon, California, Forenede Stater, 92020
        • Aclaris Investigational Site
      • Encino, California, Forenede Stater, 91436
        • Aclaris Investigational Site
      • La Jolla, California, Forenede Stater, 92093
        • Aclaris Investigational Site
      • Palm Desert, California, Forenede Stater, 92260
        • Aclaris Investigational Site
    • Florida
      • Tampa, Florida, Forenede Stater, 33613
        • Aclaris Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, Forenede Stater, 73103
        • Aclaris Investigational Site
    • Pennsylvania
      • Duncansville, Pennsylvania, Forenede Stater, 16635
        • Aclaris Investigational Site
    • Tennessee
      • Jackson, Tennessee, Forenede Stater, 38305
        • Aclaris Investigational Site
    • Texas
      • Cypress, Texas, Forenede Stater, 77429
        • Aclaris Investigational Site
      • Mesquite, Texas, Forenede Stater, 75150
        • Aclaris Investigational Site
      • San Antonio, Texas, Forenede 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
  • Tjekkiet
      • Brno, Tjekkiet, 615 00
        • Aclaris Investigational Site
      • Hlučín, Tjekkiet, 748 01
        • Aclaris Investigational Site
      • Ostrava, Tjekkiet, 702 00
        • Aclaris Investigational Site
      • Pardubice, Tjekkiet, 530 02
        • Aclaris Investigational Site
      • Prague, Tjekkiet, 128 50
        • Aclaris Investigational Site
      • Prague, Tjekkiet, 140 00
        • Aclaris Investigational Site
      • Uherské Hradiště, Tjekkiet, 686 01
        • Aclaris Investigational Site

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 75 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Medicin: Methotrexate

15 mg to 25 mg weekly

Medicin: ATI-450 20 mg oral tablet BID

Oral, small molecule MK2 inhibitor

Andre navne:
  • zunsemetinib
Eksperimentel: ATI-450 50 mg BID plus Methotrexate

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

15 mg to 25 mg weekly

Medicin: ATI-450 50 mg oral tablet BID

Oral, small molecule MK2 inhibitor

Andre navne:
  • zunsemetinib
Placebo komparator: Placebo plus Methotrexate

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

15 mg to 25 mg weekly

Medicin: Placebo oral tablet

Placebo tablet manufactured to match ATI-450 in appearance

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
Tidsramme
ATI-450 og metabolit (CDD-2164) koncentrationer
Tidsramme: 2 timer efter dosering på dag 1, 8 og 85
2 timer efter 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Aclaris Therapeutics, Inc.

Efterforskere

  • Studieleder: Ajay Aggarwal, Aclaris Therapeutics, Inc.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. februar 2022

Primær færdiggørelse (Faktiske)

5. september 2023

Studieafslutning (Faktiske)

11. oktober 2023

Datoer for studieregistrering

Først indsendt

18. februar 2022

Først indsendt, der opfyldte QC-kriterier

4. marts 2022

Først opslået (Faktiske)

15. marts 2022

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

28. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

2. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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