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ATI-450 Plus MTX Versus Placebo Plus MTX em pacientes com AR ativa moderada a grave

2 de setembro de 2026 atualizado por: Aclaris Therapeutics, Inc.

ATI-450 Plus MTX Versus Placebo Plus MTX em pacientes com AR ativa moderada a grave que tiveram uma resposta inadequada ao MTX sozinho

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.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Real)

251

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 75 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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
Medicamento: Methotrexate

15 mg to 25 mg weekly

Medicamento: ATI-450 20 mg oral tablet BID

Oral, small molecule MK2 inhibitor

Outros nomes:
  • zunsemetinibe
Experimental: ATI-450 50 mg BID plus Methotrexate

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

15 mg to 25 mg weekly

Medicamento: ATI-450 50 mg oral tablet BID

Oral, small molecule MK2 inhibitor

Outros nomes:
  • zunsemetinibe
Comparador de Placebo: Placebo plus Methotrexate

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

15 mg to 25 mg weekly

Medicamento: Placebo oral tablet

Placebo tablet manufactured to match ATI-450 in appearance

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Percentage of Participants Achieving ACR20 at Week 12
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Concentrações de ATI-450 e Metabolito (CDD-2164)
Prazo: 2 horas após a dose nos Dias 1, 8 e 85
2 horas após a dose nos Dias 1, 8 e 85
Percentage of Participants Achieving ACR50 at Week 12
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Aclaris Therapeutics, Inc.

Investigadores

  • Diretor de estudo: Ajay Aggarwal, Aclaris Therapeutics, Inc.

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

1 de fevereiro de 2022

Conclusão Primária (Real)

5 de setembro de 2023

Conclusão do estudo (Real)

11 de outubro de 2023

Datas de inscrição no estudo

Enviado pela primeira vez

18 de fevereiro de 2022

Enviado pela primeira vez que atendeu aos critérios de CQ

4 de março de 2022

Primeira postagem (Real)

15 de março de 2022

Atualizações de registro de estudo

Última Atualização Postada (Real)

28 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

2 de setembro de 2026

Última verificação

1 de setembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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