Tocilizumab for Patients With Giant Cell Arteritis
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Giant Cell Arteritis |
Drug: Tocilizumab + Glucocorticoids (GCs) Drug: Placebo + Glucocorticoids (GCs) |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Phase II, Randomized, Double-blind, Placebo Controlled Study of Tocilizumab in Patients With Giant Cell Arteritis |
- Proportion of patients that have achieved complete remission of disease [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Proportion of relapse free patients [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Cumulative dose of GCs in mg [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Time to first relapse after induction of remission [ Time Frame: 12 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 27 |
| Study Start Date: | September 2011 |
| Estimated Study Completion Date: | March 2014 |
| Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Tocilizumab
Tocilizumab 8mg/kg every 4 weeks until week 52.
|
Drug: Tocilizumab + Glucocorticoids (GCs)
Tocilizumab 8mg/kg every 4 weeks until week 52.
|
|
Placebo Comparator: Placebo
Placebo every 4 weeks until week 52.
|
Drug: Placebo + Glucocorticoids (GCs)
Placebo every 4 weeks until week 52.
|
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).
Eligibility| Ages Eligible for Study: | 50 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Peter M Villiger, Prof. | +41 31 632 80 17 | PeterM.Villiger@insel.ch |
| Contact: Michael Seitz, Prof. | +41 31 632 80 17 | MichaelN.Seitz@insel.ch |
| Switzerland | |
| Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital | Recruiting |
| Bern, Switzerland, 3010 | |
| Principal Investigator: Michael Seitz, Prof | |
| 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 |
More Information
No publications provided
| Responsible Party: | Proff. P.M.Villiger and M.Seitz, Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital, Bern, Switzerland |
| ClinicalTrials.gov Identifier: | NCT01450137 History of Changes |
| Other Study ID Numbers: | 168/10 |
| Study First Received: | October 3, 2011 |
| Last Updated: | January 29, 2013 |
| Health Authority: | Switzerland: Ethikkommission Switzerland: Swissmedic |
Keywords provided by University Hospital Inselspital, Berne:
|
Giant Cell Arteritis Tocilizumab Antibodies, Monoclonal Glucocorticoids |
Additional relevant MeSH terms:
|
Giant Cell Arteritis Polymyalgia Rheumatica Arteritis Vascular Diseases Cardiovascular Diseases Vasculitis Vasculitis, Central Nervous System Autoimmune Diseases of the Nervous System Nervous System Diseases Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Skin Diseases, Vascular |
Skin Diseases Autoimmune Diseases Immune System Diseases Muscular Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 22, 2013