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Tocilizumab for Patients With Giant Cell Arteritis

18. september 2018 oppdatert av: 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.

Studieoversikt

Detaljert beskrivelse

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).

Studietype

Intervensjonell

Registrering (Faktiske)

30

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

50 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Tocilizumab
Tocilizumab 8mg/kg every 4 weeks until week 52.
Tocilizumab 8mg/kg every 4 weeks until week 52.
Placebo komparator: Placebo
Placebo every 4 weeks until week 52.
Placebo every 4 weeks until week 52.

Hva måler studien?

Primære resultatmål

Resultatmål
Tidsramme
Number of Patients That Have Achieved Complete Remission of Disease
Tidsramme: 12 weeks
12 weeks

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Relapse Free Patients
Tidsramme: 12 months
12 months
Cumulative Dose of GCs in mg/kg
Tidsramme: 12 months
cumulative weight-adapted prednisolone dose
12 months
Restricted Mean Survival Time to First Relapse After Induction of Remission
Tidsramme: 12 months
12 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Samarbeidspartnere

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. september 2011

Primær fullføring (Faktiske)

1. desember 2014

Studiet fullført (Faktiske)

1. september 2015

Datoer for studieregistrering

Først innsendt

3. oktober 2011

Først innsendt som oppfylte QC-kriteriene

11. oktober 2011

Først lagt ut (Anslag)

12. oktober 2011

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

12. februar 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

18. september 2018

Sist bekreftet

1. september 2018

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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3
Abonnere