Giant Cell ArteritisPhase 2NCT01450137

Tocilizumab for Patients With Giant Cell Arteritis

A Phase 2 study testing Tocilizumab + Glucocorticoids (GCs) in people with Giant Cell Arteritis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 50 years and older
Conditions the study is for: Giant Cell Arteritis
What is being tested?: Tocilizumab + Glucocorticoids (GCs)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 30 participants
Where: 1 siteSwitzerland
Study dates: Sep 2011to Sep 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 20Show fewer

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

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

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

Other trials in Switzerland

About this study

Official title: 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.

Read the detailed description

Background

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

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).

Conditions: Giant Cell Arteritis
Being tested: Tocilizumab + Glucocorticoids (GCs), Placebo + Glucocorticoids (GCs)
Keywords: Giant Cell Arteritis, Tocilizumab, Antibodies, Monoclonal, Glucocorticoids
Medical subject headings: Giant Cell Arteritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tocilizumab + Glucocorticoids (GCs)Drug
Tocilizumab 8mg/kg every 4 weeks until week 52.
Placebo + Glucocorticoids (GCs)Drug
Placebo every 4 weeks until week 52.

Study groups in NCT01450137
Study group	Role	What they receive
Tocilizumab	Experimental	Tocilizumab 8mg/kg every 4 weeks until week 52. Receives: Drug: Tocilizumab + Glucocorticoids (GCs)
Placebo	Placebo comparator	Placebo every 4 weeks until week 52. Receives: Drug: Placebo + Glucocorticoids (GCs)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (3)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011Sep 2015

First posted12 Oct 2011 (estimated)
Study startSep 2011
Primary completionDec 2014
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Giant Cell ArteritisStudies of the same condition, open and under way.
More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01450137
Sponsor's protocol ID: 168/10
Status last verified: Sep 2018
First submitted: 3 Oct 2011
Last updated: 12 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 26952547
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.
PubMed 29961816

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 3
Aspirin for the Prevention of Ischemic Complications in Giant Cell Arteritis
Giant Cell Arteritis (GCA), Acute Coronary Syndrome (ACS)
RecruitingObservational study
Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
Takayasu's Arteritis, Giant Cell Arteritis
RecruitingObservational study
Optic Nerve Sheath Ultrasound in Giant Cell Arteritis
Giant Cell Arteritis, Anterior Ischemic Optic Neuropathy
Active, not recruitingObservational study
The Applanation Tonometry in GCA Pilot
Giant Cell Arteritis
RecruitingObservational study
Early Temporal Dynamics of Optic Nerve Sheath Diameter After Therapy in GCA
Giant Cell Arteritis, Temporal Arteritis

All Giant Cell Arteritis trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Randomized, Double-blind, Placebo Controlled Study of Tocilizumab in Patients With Giant Cell Arteritis
ClinicalTrials.gov ID: NCT01450137
Acronym / sponsor ID: 168/10
Conditions: Giant Cell Arteritis
Keywords: Giant Cell Arteritis, Tocilizumab, Antibodies, Monoclonal, Glucocorticoids
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Insel Gruppe AG, University Hospital BernUniversity, hospital or other
Collaborators: University of Bern, Roche Pharma AG
Study start: Sep 2011
Primary completion: Dec 2014 (actual)
Study completion: Sep 2015 (actual)
First posted: 12 Oct 2011 (estimated)
Results: Posted 12 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

Detailed description

Background

Therefore, novel therapies are needed that effectively reduce the dose and duration of GC treatment and provide more durable remissions of GCA.

Objective

Methods

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Tocilizumab	Experimental	Drug: Tocilizumab + Glucocorticoids (GCs)Tocilizumab 8mg/kg every 4 weeks until week 52.
Placebo	Placebo comparator	Drug: Placebo + Glucocorticoids (GCs)Placebo every 4 weeks until week 52.

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Patients with newly onset or relapsed GCA
> 50 years of age
satisfying ACR criteria
elevated sedimentation rate above 40 mm
CRP > 20 mg/L

Key exclusion criteria (20 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tocilizumab + Glucocorticoids (GCs)Tocilizumab 8mg/kg every 4 weeks until week 52.	Drug	Tocilizumab
Placebo + Glucocorticoids (GCs)Placebo every 4 weeks until week 52.	Drug	Placebo

Primary outcome

Number of Patients That Have Achieved Complete Remission of Disease
Time frame: 12 weeks

3 secondary outcomes

Number of Relapse Free Patients
Time frame: 12 months
Cumulative Dose of GCs in mg/kg
Time frame: 12 months
Restricted Mean Survival Time to First Relapse After Induction of Remission
Time frame: 12 months

Results and safety

Results posted to the registry on 12 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tocilizumab	20	18
Placebo	10	7

Primary outcome: Number of Patients That Have Achieved Complete Remission of Disease

Time frame: 12 weeks. Count of participants. Unit: Participants

Measure	Tocilizumab n = 20	Placebo n = 10
Value	17	4

Tocilizumab vs Placebo: Risk Difference (RD): 0.45 (95% CI 0.11 to 0.79), p = 0.0301, Fisher Exact

Population analysed: All randomized patients, intention-to-treat

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tocilizumab	7 of 20 (35%)	11 of 20 (55%)	0 of 20
Placebo	5 of 10 (50%)	6 of 10 (60%)	1 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26952547Villiger 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.
Derived from this study: PubMed 29961816Gloor 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.

Related trials for Giant Cell Arteritis

Not yet recruitingPhase 3
Aspirin for the Prevention of Ischemic Complications in Giant Cell Arteritis
Giant Cell Arteritis (GCA), Acute Coronary Syndrome (ACS)
RecruitingObservational study
Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
Takayasu's Arteritis, Giant Cell Arteritis
RecruitingObservational study
Optic Nerve Sheath Ultrasound in Giant Cell Arteritis
Giant Cell Arteritis, Anterior Ischemic Optic Neuropathy
Active, not recruitingObservational study
The Applanation Tonometry in GCA Pilot
Giant Cell Arteritis
RecruitingObservational study
Early Temporal Dynamics of Optic Nerve Sheath Diameter After Therapy in GCA
Giant Cell Arteritis, Temporal Arteritis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Peter M Villiger, Prof principal investigator

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

Michael Seitz, Prof principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tocilizumab + Glucocorticoids (GCs) in people with Giant Cell Arteritis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients That Have Achieved Complete Remission of Disease (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01450137, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.