- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01450137
Tocilizumab for Patients With Giant Cell Arteritis
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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Bern, Svizzera, 3010
- Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Tocilizumab
Tocilizumab 8mg/kg every 4 weeks until week 52.
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Tocilizumab 8mg/kg every 4 weeks until week 52.
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Comparatore placebo: Placebo
Placebo every 4 weeks until week 52.
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Placebo every 4 weeks until week 52.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Number of Patients That Have Achieved Complete Remission of Disease
Lasso di tempo: 12 weeks
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12 weeks
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Number of Relapse Free Patients
Lasso di tempo: 12 months
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12 months
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Cumulative Dose of GCs in mg/kg
Lasso di tempo: 12 months
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cumulative weight-adapted prednisolone dose
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12 months
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Restricted Mean Survival Time to First Relapse After Induction of Remission
Lasso di tempo: 12 months
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12 months
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Collaboratori e investigatori
Investigatori
- Investigatore principale: Peter M Villiger, Prof, Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
- Investigatore principale: Michael Seitz, Prof, Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
Pubblicazioni e link utili
Pubblicazioni generali
- Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, Butikofer L, Seitz M, Reichenbach S. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016 May 7;387(10031):1921-7. doi: 10.1016/S0140-6736(16)00560-2. Epub 2016 Mar 4.
- Gloor AD, Yerly D, Adler S, Reichenbach S, Kuchen S, Seitz M, Villiger PM. Immuno-monitoring reveals an extended subclinical disease activity in tocilizumab-treated giant cell arteritis. Rheumatology (Oxford). 2018 Oct 1;57(10):1795-1801. doi: 10.1093/rheumatology/key158.
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattia cardiovascolare
- Malattie vascolari
- Disturbi cerebrovascolari
- Malattie del cervello
- Malattie del sistema nervoso centrale
- Malattie del sistema nervoso
- Malattie della pelle
- Malattie del sistema immunitario
- Malattie autoimmuni del sistema nervoso
- Malattie autoimmuni
- Malattie muscoloscheletriche
- Malattie reumatiche
- Malattie del tessuto connettivo
- Malattie muscolari
- Vasculite
- Malattie della pelle, vascolari
- Vasculite, sistema nervoso centrale
- Polimialgia reumatica
- Arterite a cellule giganti
- Arterite
- Effetti fisiologici delle droghe
- Ormoni
- Ormoni, sostituti ormonali e antagonisti ormonali
- Glucocorticoidi
Altri numeri di identificazione dello studio
- 168/10
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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