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Tocilizumab for Patients With Giant Cell Arteritis

18 de setembro de 2018 atualizado por: University Hospital Inselspital, Berne

A Phase II, Randomized, Double-blind, Placebo Controlled Study of Tocilizumab in Patients With Giant Cell Arteritis

Giant-cell arteritis (GCA) is an immune-mediated disease that mostly affects people older than 50 years of age. Glucocorticoid (GC) treatment dramatically alters the symptoms and course of GCA, reducing the likelihood of vascular complications that could lead e.g. to blindness. However, relapses usually occur when GC dosages are tapered, resulting in frequent re-treatment with high cumulative dosages of GC over time with substantial toxicity and morbidity (e.g. diabetes mellitus, infections, enhanced cardiovascular risk, osteoporotic fractures, cataracts).

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the human interleukin-6 receptor (IL-6R). Elevated tissue and serum levels of IL-6 have been implicated in giant cell arteritis. Inhibition of IL-6 and/or its receptor therefore represents a new and novel approach for the treatment of RA.

The primary endpoint is the proportion of patients that have achieved complete remission of disease after treatment with TCZ compared to treatment with placebo at week 12. All patients will receive glucocorticoids in a standardized form.

Visão geral do estudo

Descrição detalhada

Background

Giant-cell arteritis (GCA) is an immune-mediated disease that mostly affects people older than 50 years of age. Glucocorticoid (GC) treatment dramatically alters the symptoms and course of GCA, reducing the likelihood of vascular complications that could lead e.g. to blindness. However, relapses usually occur when GC dosages are tapered, resulting in frequent re-treatment with high cumulative dosages of GC over time with substantial toxicity and morbidity (e.g. diabetes mellitus, infections, enhanced cardiovascular risk, osteoporotic fractures, cataracts).

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the human interleukin-6 receptor (IL-6R). Elevated tissue and serum levels of IL-6 have been implicated in giant cell arteritis. Inhibition of IL-6 and/or its receptor therefore represents a new and novel approach for the treatment of RA.

Objective

The primary endpoint is the proportion of patients that have achieved complete remission of disease (normal ESR and CRP + absence of signs and symptoms) at Week 12 at a GC dose of 0.1 mg/kg/d of prednisone.

Methods

2-arm (Tocilizumab + Glucocorticoids (GCs) vs. Placebo + GCs), randomized, placebo-controlled, double blind, monocentric trial in patients with newly onset or relapsing giant cell arteritis (GCA), satisfying ACR criteria AND an elevated sedimentation rate above 40 mm/h and a CRP > 20 mg/L AND a biopsy proven GCA OR a large vessel vasculitis assessed by MR Angiography (MRA).

Tipo de estudo

Intervencional

Inscrição (Real)

30

Estágio

  • Fase 2

Contactos e Locais

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Locais de estudo

      • Bern, Suíça, 3010
        • Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital

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

50 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Patients with newly onset or relapsed GCA
  • > 50 years of age
  • satisfying ACR criteria
  • elevated sedimentation rate above 40 mm
  • CRP > 20 mg/L
  • Patients with histologically proven GCA or with large vessel vasculitis assessed by MRI

Exclusion Criteria

  • Rheumatic diseases (except for CPPD/chondrocalcinosis) other than GCA/Takayasu disease or polymyalgia rheumatica (i.e., RA, autoimmune connectivitides, other systemic vasculitides, a.o.)
  • Evidence of significant and/or uncontrolled concomitant disease
  • Diagnosis of GCA > 4 weeks before screening visit and beginning of GC treatment > 4 weeks before screening (only valid for new onset GCA), or when a patient received treatment with tocilizumab or with other biological agents (such as TNFα-blockers) within 3 months before screening
  • Any condition or general state of health which, in the Investigator's opinion, would preclude participation in the study
  • Actual or recent myocardial infarction (within the last 3 months before screening visit)
  • Significant cardiac disease (NYHA Class III and IV), known severe chronic obstructive pulmonary disease (COPD) (FEV1 < 50% predicted or Functional dyspnoea > Grade 3 on the MRC Dyspnoea Scale) or other significant pulmonary disease
  • Uncontrolled disease (such as asthma, psoriasis or inflammatory bowel disease) where flares are commonly treated with oral or injectable corticosteroids
  • Known active infection of any kind, or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to baseline
  • History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline
  • Any surgical procedure, including bone/joint surgery within 8 weeks prior to baseline or planned within the duration of the study
  • History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to screening)
  • Lack of peripheral venous access
  • Body weight > 150 kg or BMI > 35
  • Previous treatment with tocilizumab or any other biological agent
  • Treatment with any investigational agent within 28 days of screening or 5 half-lives of the investigational drug (whichever is the longer)
  • History of severe allergic or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of tocilizumab (RoActemra)
  • Receipt of any vaccine within 28 days prior to baseline (a patient's vaccination record and need for immunization prior to receiving tocilizumab/placebo must be carefully investigated)
  • Positive tests for hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HbcAb) or hepatitis C serology
  • Positive Quantiferon-TB® test for latent Tb without subsequent INH prophylaxis
  • Patients with active Tb which had to be treated for Tb within 2 years before the screening visit

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: Tocilizumab
Tocilizumab 8mg/kg every 4 weeks until week 52.
Tocilizumab 8mg/kg every 4 weeks until week 52.
Comparador de Placebo: Placebo
Placebo every 4 weeks until week 52.
Placebo every 4 weeks until week 52.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
Number of Patients That Have Achieved Complete Remission of Disease
Prazo: 12 weeks
12 weeks

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Number of Relapse Free Patients
Prazo: 12 months
12 months
Cumulative Dose of GCs in mg/kg
Prazo: 12 months
cumulative weight-adapted prednisolone dose
12 months
Restricted Mean Survival Time to First Relapse After Induction of Remission
Prazo: 12 months
12 months

Colaboradores e Investigadores

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

Investigadores

  • Investigador principal: Peter M Villiger, Prof, Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
  • Investigador principal: Michael Seitz, Prof, Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital

Publicações e links úteis

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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 setembro de 2011

Conclusão Primária (Real)

1 de dezembro de 2014

Conclusão do estudo (Real)

1 de setembro de 2015

Datas de inscrição no estudo

Enviado pela primeira vez

3 de outubro de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

11 de outubro de 2011

Primeira postagem (Estimativa)

12 de outubro de 2011

Atualizações de registro de estudo

Última Atualização Postada (Real)

12 de fevereiro de 2019

Última atualização enviada que atendeu aos critérios de controle de qualidade

18 de setembro de 2018

Última verificação

1 de setembro de 2018

Mais Informações

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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