Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis (986)
25 de julho de 2017 atualizado por: Biotest
A 24-week Phase IIb, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Tregalizumab (BT061) in Combination With Methotrexate in the Treatment of Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Alone, Followed by a 24-week Extension Phase: T Cell REgulating Arthritis Trial 2b (TREAT 2b)
The purpose of this study is to determine the efficacy and safety of three different Tregalizumab doses in combination with Methotrexate (MTX) in subjects who have active rheumatoid arthritis and an inadequate response to MTX alone.
The overall study duration is 24 weeks followed by a 24 week extension phase.
Visão geral do estudo
Status
Rescindido
Condições
Intervenção / Tratamento
Descrição detalhada
The planned clinical study 986 (TREAT 2b) is a 24-week study in patients with Active rheumatoid arthritis (RA) who have had an inadequate response to Methotrexate (MTX) alone. The main phase of this study is followed by a 24-week extension phase for subjects meeting the respective entry criteria. Patients will be randomized to one of three different Active treatment groups or Placebo. The primary efficacy variable is the proportion of subjects with an ACR20 response after 12 weeks of double blinded treatment with the study medication based on observed cases in the FAS.
At Week 12, all subjects who had a minimum improvement of at least 20% (from baseline) in their tender joint count (TJC) and swollen joint count (SJC) continued on the same treatment. Subjects who had not demonstrated an improvement of at least 20% of TJC and SJC were assessed as non-responders. Non-responders who received placebo were randomized to an active treatment dose in a blinded manner. Non-responders who received active treatment were rolled up to the next highest dose in a blinded manner, apart from those already on the highest dose. These subjects remained on the highest dose.
Tipo de estudo
Intervencional
Inscrição (Real)
321
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
-
-
-
Berlin, Alemanha
- Study Site 03
-
Frankfurt, Alemanha
- Study Site 04
-
Muenchen, Alemanha
- Study Site 06
-
Ratingen, Alemanha
- Study Site 02
-
Zerbst, Alemanha
- Study site 01
-
-
-
-
-
Plovdiv, Bulgária
- Study site 01
-
Plovdiv, Bulgária
- Study Site 06
-
Sofia, Bulgária
- Study Site 02
-
Sofia, Bulgária
- Study Site 04
-
Sofia, Bulgária
- Study Site 07
-
Stara Zagora, Bulgária
- Study Site 05
-
Varna, Bulgária
- Study Site 03
-
-
-
-
Quebec
-
Rimouski, Quebec, Canadá
- Study Site 02
-
St-Jérôme, Quebec, Canadá
- Study site 01
-
-
-
-
-
Bratislava, Eslováquia
- Study Site 03
-
Kosice - Saca, Eslováquia
- Study Site 04
-
Lucenec, Eslováquia
- Study Site 05
-
Povazska Bystrica, Eslováquia
- Study Site 02
-
Rimavska Sobota, Eslováquia
- Study site 01
-
-
-
-
Arizona
-
Paradise Valley, Arizona, Estados Unidos, 85253
- Study Site 07
-
-
Illinois
-
Springfield, Illinois, Estados Unidos, 62704
- Study site 01
-
-
Nebraska
-
Lincoln, Nebraska, Estados Unidos, 68516
- Study Site 03
-
-
New Jersey
-
Clifton, New Jersey, Estados Unidos, 07012
- Study Site 02
-
-
South Carolina
-
North Charleston, South Carolina, Estados Unidos, 29406
- Study Site 04
-
-
Tennessee
-
Jackson, Tennessee, Estados Unidos, 38305
- Study Site 05
-
-
Texas
-
Houston, Texas, Estados Unidos, 77004
- Study site 09
-
Katy, Texas, Estados Unidos, 77450
- Study site 10
-
-
-
-
-
Tallinn, Estônia
- Study site 01
-
-
-
-
-
Kemerovo, Federação Russa
- Study Site 08
-
Kemerovo, Federação Russa
- Study site 11
-
Kursk, Federação Russa
- Study Site 04
-
Moscow, Federação Russa
- Study Site 03
-
Moscow, Federação Russa
- Study Site 07
-
Moscow, Federação Russa
- Study site 10
-
Omsk, Federação Russa
- Study Site 05
-
Saratov, Federação Russa
- Study site 09
-
Smolensk, Federação Russa
- Study Site 06
-
Tomsk, Federação Russa
- Study site 01
-
Yaroslavl, Federação Russa
- Study Site 02
-
-
-
-
-
Balatonfüred, Hungria
- Study Site 03
-
Budapest, Hungria
- Study Site 02
-
Budapest, Hungria
- Study Site 04
-
Budapest, Hungria
- Study Site 05
-
Gyula, Hungria
- Study Site 06
-
Veszprem, Hungria
- Study site 01
-
-
-
-
-
Kaunas, Lituânia
- Study site 01
-
Vilnus, Lituânia
- Study Site 02
-
-
-
-
-
Chihuahua, México
- Study Site 02
-
Distrito Federal, México
- Study Site 03
-
-
Distrito Federal
-
Mexico, Distrito Federal, México
- Study Site 05
-
Mexico, Distrito Federal, México
- Study Site 08
-
-
Guanajuato
-
Leon, Guanajuato, México
- Study Site 06
-
-
-
-
-
Bialystok, Polônia
- Study Site 08
-
Bydgoszcz, Polônia
- Study Site 05
-
Elblag, Polônia
- Study site 10
-
Gdynia, Polônia
- Study Site 04
-
Katowice, Polônia
- Study Site 02
-
Krakow, Polônia
- Study Site 03
-
Krakow, Polônia
- Study Site 06
-
Poznan, Polônia
- Study site 09
-
Warszawa, Polônia
- Study site 01
-
Warszawa, Polônia
- Study Site 07
-
-
-
-
-
Belgrade, Sérvia
- Study site 01
-
Belgrade, Sérvia
- Study Site 02
-
Belgrade, Sérvia
- Study Site 04
-
Niska Banja, Sérvia
- Study Site 03
-
-
-
-
-
Bruntal, Tcheca
- Study Site 03
-
Ostrava, Tcheca
- Study Site 05
-
Praha, Tcheca
- Study site 01
-
Praha, Tcheca
- Study Site 04
-
Praha, Tcheca
- Study Site 08
-
Praha, Tcheca
- Study site 09
-
Uherske Hradiste, Tcheca
- Study Site 02
-
Uherske Hradiste, Tcheca
- Study Site 07
-
Zlin, Tcheca
- Study Site 06
-
-
-
-
-
Donetsk, Ucrânia
- Study Site 08
-
Kharkiv, Ucrânia
- Study site 01
-
Kharkiv, Ucrânia
- Study Site 02
-
Kyiv, Ucrânia
- Study Site 03
-
Kyiv, Ucrânia
- Study Site 04
-
Vinnytsia, Ucrânia
- Study Site 05
-
Vinnytsia, Ucrânia
- Study Site 06
-
Vinnytsia, Ucrânia
- Study Site 07
-
Zaporizhzhia, Ucrânia
- Study site 09
-
-
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:
- Subject demonstrates active RA according to the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA with functional class I-III for ≥6 months.
- Subject receives oral or parenteral MTX treatment for ≥12 weeks (overall), with an unchanged mode of application and stable MTX dose of ≥15 mg per week (or ≥12.5 mg per week in case of MTX intolerance), but no more than the highest locally approved dose for RA, for ≥8 weeks prior to baseline. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons. If applicable, the dose of folic acid must be unchanged for ≥8 weeks prior to baseline.
- Subject meets the following two criteria at both screening and baseline: - At least 6 swollen joints at 28-joint assessment. - At least 6 tender joints at 28-joint assessment.
- Subject has an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) above the upper limit of normal (ULN) at screening. These tests may be repeated once during the screening period at the discretion of the investigator.
- Subject is ≥18 and ≤75 years of age.
- Subject has a body mass index ≥18 and ≤35 kg/m².
- Subject receives treatment with corticosteroids ≤10 mg prednisone equivalent, stable for at least 4 weeks prior to baseline and during the study, if applicable.
- Subject receives treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable for at least 2 weeks prior to baseline and during the study, if applicable.
- Female subjects of childbearing potential: has both a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
- Subject is judged to be in good general health as determined by the investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (within 3 months before screening date is acceptable), and 12-lead electrocardiogram (ECG).
- Subject has a cluster of differentiation 4 (CD4) cell count of > 400/µl at screening.
Exclusion Criteria:
- Subject has previous exposure to any systemic biologic therapy (e.g., etanercept, adalimumab, rituximab, abatacept, tocilizumab), to Janus kinase (JAK) or spleen tyrosine kinase (SYK) inhibitors, or to Tregalizumab. Previous treatment with an anti-TNF agent is allowed only, if all of the following criteria apply: - treatment was stopped for reasons other than lack of efficacy or adverse events (AEs) - treatment was stopped at least 12 weeks or five half-lives of the compound prior to baseline (whichever is longer), and - the treatment period did not exceed 6 weeks.
- Subject received treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) apart from MTX in the 12 weeks prior to baseline, and for DMARD leflunomide in the 24 weeks prior to baseline (except where specific leflunomide wash-out procedures were completed, following applicable guidelines).
- Subject has been treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to baseline. Inhaled corticosteroids for stable medical conditions are allowed.
- Subject has undergone joint surgery in the 12 weeks prior to baseline (at joints to be assessed within the study) or has undergone major surgery (e.g., abdominal surgery) in the 8 weeks prior to baseline.
- Subject has a history of acute inflammatory joint disease of an origin other than RA or subject has any other rheumatic disease other than RA (e.g., mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter's syndrome, fibromyalgia, systemic lupus erythematosus or any arthritis with onset prior to age 17 years). However, subjects may have secondary Sjögren's syndrome.
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: Dose Level 1 Tregalizumab
25mg Tregalizumab s.c. weekly
|
humanized anti-CD4 mAb
Outros nomes:
|
|
Experimental: Dose Level 2 Tregalizumab
100mg Tregalizumab s.c. weekly
|
humanized anti-CD4 mAb
Outros nomes:
|
|
Experimental: Dose Level 3 Tregalizumab
200mg Tregalizumab s.c. weekly
|
humanized anti-CD4 mAb
Outros nomes:
|
|
Comparador de Placebo: Placebo
Placebo s.c. weekly
|
identical end formulation buffer
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
The Proportion of Subjects Who Achieve an ACR20 at Week 12 Following Treatment With Tregalizumab + MTX Compared With Subjects Treated on Placebo + MTX
Prazo: Week 12
|
The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS. |
Week 12
|
Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
|
Proportions of Subjects With an ACR 20 Response.
Prazo: Week 24
|
Week 24
|
|
Proportions of Subjects With an ACR 50 & 70 Response.
Prazo: Week 12 & Week 24
|
Week 12 & Week 24
|
|
Proportions of Subjects With an Disease Activity Score DAS28 <2.6
Prazo: Week 12 & Week 24
|
Week 12 & Week 24
|
|
Proportions of Subjects With Low Disease Activity DAS28 ≤3.2
Prazo: Week 12 & Week 24
|
Week 12 & Week 24
|
|
ACR Score
Prazo: up to 48 weeks
|
up to 48 weeks
|
|
Simple Disease Activity Index [SDAI] ≤11
Prazo: week 12 & 24
|
week 12 & 24
|
|
Clinical Disease Activity Index [CDAI] ≤10
Prazo: week 12 & 24
|
week 12 & 24
|
|
DAS28
Prazo: up to 48 weeks
|
up to 48 weeks
|
|
EULAR Response
Prazo: up to 48 weeks
|
up to 48 weeks
|
|
ACR Score Individual Components
Prazo: up to 48 weeks
|
up to 48 weeks
|
|
DAS28 Score Individual Components
Prazo: up to 48 weeks
|
up to 48 weeks
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Pharmacokinetics
Prazo: up to 48 weeks
|
AUC, Cmax, Tmax at baseline, and at Week (W) 2/Visit (V) 4, W4/V5, W8/V7, W12/V8, W24/V10, W3/V122, W48 (end of Treatment [EoT]/ early termination ET), and at follow-up (post EoT/post ET).
|
up to 48 weeks
|
|
Evaluation of Safety, Patient Reported Outcomes & Blood Tests.
Prazo: up to 48 weeks
|
up to 48 weeks
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
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
1 de outubro de 2013
Conclusão Primária (Real)
1 de julho de 2015
Conclusão do estudo (Real)
1 de julho de 2015
Datas de inscrição no estudo
Enviado pela primeira vez
17 de novembro de 2013
Enviado pela primeira vez que atendeu aos critérios de CQ
2 de dezembro de 2013
Primeira postagem (Estimativa)
3 de dezembro de 2013
Atualizações de registro de estudo
Última Atualização Postada (Real)
24 de agosto de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
25 de julho de 2017
Última verificação
1 de julho de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 986_TREAT 2b
- 2013-000114-38 (Número EudraCT)
- BT986 (Outro identificador: Biotest AG)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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 .