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Trial record 35 of 130 for:    GCA

Tocilizumab for Patients With Giant Cell Arteritis

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ClinicalTrials.gov Identifier: NCT01450137
Recruitment Status : Completed
First Posted : October 12, 2011
Results First Posted : February 12, 2019
Last Update Posted : February 12, 2019
Sponsor:
Collaborators:
University of Bern
Roche Pharma AG
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Tracking Information
First Submitted Date  ICMJE October 3, 2011
First Posted Date  ICMJE October 12, 2011
Results First Submitted Date  ICMJE July 3, 2017
Results First Posted Date  ICMJE February 12, 2019
Last Update Posted Date February 12, 2019
Study Start Date  ICMJE September 2011
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
Number of Patients That Have Achieved Complete Remission of Disease [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2011)
Proportion of patients that have achieved complete remission of disease [ Time Frame: 12 weeks ]
Change History Complete list of historical versions of study NCT01450137 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
  • Number of Relapse Free Patients [ Time Frame: 12 months ]
  • Cumulative Dose of GCs in mg/kg [ Time Frame: 12 months ]
    cumulative weight-adapted prednisolone dose
  • Restricted Mean Survival Time to First Relapse After Induction of Remission [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2011)
  • Proportion of relapse free patients [ Time Frame: 12 months ]
  • Cumulative dose of GCs in mg [ Time Frame: 12 months ]
  • Time to first relapse after induction of remission [ Time Frame: 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tocilizumab for Patients With Giant Cell Arteritis
Official Title  ICMJE A Phase II, Randomized, Double-blind, Placebo Controlled Study of Tocilizumab in Patients With Giant Cell Arteritis
Brief Summary

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.

Detailed Description

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Giant Cell Arteritis
Intervention  ICMJE
  • Drug: Tocilizumab + Glucocorticoids (GCs)
    Tocilizumab 8mg/kg every 4 weeks until week 52.
  • Drug: Placebo + Glucocorticoids (GCs)
    Placebo every 4 weeks until week 52.
Study Arms  ICMJE
  • Experimental: Tocilizumab
    Tocilizumab 8mg/kg every 4 weeks until week 52.
    Intervention: Drug: Tocilizumab + Glucocorticoids (GCs)
  • Placebo Comparator: Placebo
    Placebo every 4 weeks until week 52.
    Intervention: Drug: Placebo + Glucocorticoids (GCs)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 23, 2015)
30
Original Estimated Enrollment  ICMJE
 (submitted: October 11, 2011)
27
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01450137
Other Study ID Numbers  ICMJE 168/10
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital Inselspital, Berne
Study Sponsor  ICMJE University Hospital Inselspital, Berne
Collaborators  ICMJE
  • University of Bern
  • Roche Pharma AG
Investigators  ICMJE
Principal Investigator: Peter M Villiger, Prof Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
Principal Investigator: Michael Seitz, Prof Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital
PRS Account University Hospital Inselspital, Berne
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP