Tocilizumab for Patients With Giant Cell Arteritis

NCT01450137 | Completed Phase 2 Results DMC

• 1 other identifier: 168/10
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Giant Cell Arteritis

Keywords

Giant Cell Arteritis; Tocilizumab; Antibodies, Monoclonal; Glucocorticoids

Outcome Measures

Primary Outcomes (1)

• Number of Patients That Have Achieved Complete Remission of Disease

  12 weeks

Secondary Outcomes (3)

• Number of Relapse Free Patients

  12 months

• Cumulative Dose of GCs in mg/kg

  12 months

• Restricted Mean Survival Time to First Relapse After Induction of Remission

  12 months

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Tocilizumab 8mg/kg every 4 weeks until week 52.

Drug: Tocilizumab + Glucocorticoids (GCs)

Placebo

PLACEBO COMPARATOR

Placebo every 4 weeks until week 52.

Drug: Placebo + Glucocorticoids (GCs)

Interventions

Tocilizumab + Glucocorticoids (GCs) DRUG

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab

Placebo + Glucocorticoids (GCs) DRUG

Placebo every 4 weeks until week 52.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

Department of Rheumatology, Clinical Immunology Allergology, University Hospital, Inselspital

Bern, 3010, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 26952547 RESULT

• 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.

  PMID: 29961816 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

tocilizumab; Glucocorticoids

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Prof Peter M Villiger
• Organization: Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

peter.villiger@insel.ch

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2011
• First Posted: October 12, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: September 1, 2015
• Last Updated: February 12, 2019
• Results First Posted: February 12, 2019

Record last verified: 2018-09

Locations

CH (1)