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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03600805




Registration number
NCT03600805
Ethics application status
Date submitted
17/07/2018
Date registered
26/07/2018
Date last updated
13/08/2019

Titles & IDs
Public title
Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA
Scientific title
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Giant Cell Arteritis
Secondary ID [1] 0 0
2017-002988-18
Secondary ID [2] 0 0
EFC15068
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Giant Cell Arteritis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Neurological 0 0 0 0
Other neurological disorders
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sarilumab SAR153191
Treatment: Drugs - Sarilumab matching placebo
Treatment: Drugs - Prednisone
Treatment: Drugs - Prednisone matching placebo

Experimental: Group A - Sarilumab dose 1, once every 2 weeks plus 26-week prednisone taper regimen

Experimental: Group B - Sarilumab dose 2, once every 2 weeks plus 26-week prednisone taper regimen

Placebo Comparator: Group C - Sarilumab matching placebo once every 2 weeks plus prednisone regimen 26 weeks

Placebo Comparator: Group D - Sarilumab matching placebo once every 2 weeks plus prednisone regimen 52 weeks


Treatment: Drugs: Sarilumab SAR153191
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Treatment: Drugs: Sarilumab matching placebo
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Treatment: Drugs: Prednisone
Pharmaceutical form:tablets or capsules Route of administration: oral administration

Treatment: Drugs: Prednisone matching placebo
Pharmaceutical form:capsules Route of administration: oral administration

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of patients with sustained remission - Proportion of patients achieving sustained remission at Week 52.
Timepoint [1] 0 0
At Week 52
Secondary outcome [1] 0 0
Components of sustained remission (composite measure) - Summary of the components of the sustained remission composite measure at Week 52
Timepoint [1] 0 0
At Week 52
Secondary outcome [2] 0 0
Cumulative corticosteroid dose - Total cumulative corticosteroid (including prednisone) dose over 52 weeks
Timepoint [2] 0 0
Up to Week 52
Secondary outcome [3] 0 0
Time to first GCA flare - Duration of first GCA flare from clinical remission up to Week 52
Timepoint [3] 0 0
Up to Week 52
Secondary outcome [4] 0 0
Change in glucocorticoid toxicity index - Changes from baseline in the glucocorticoid toxicity index and its components up to Week 52
Timepoint [4] 0 0
Up to Week 52
Secondary outcome [5] 0 0
Adverse events - Number of adverse events
Timepoint [5] 0 0
Up to Week 76
Secondary outcome [6] 0 0
Pharmacokinetic - Serum concentrations of sarilumab
Timepoint [6] 0 0
Up to Week 58

Eligibility
Key inclusion criteria
Inclusion criteria :

- Diagnosis of giant cell arteritis (GCA) according to European League Against
Rheumatism/American College of Rheumatology classification criteria.

- New onset active disease or refractory active disease.

- At least one of the symptoms of GCA within 6 weeks of baseline.

- Either erythrocyte sedimentation rate =30 mm/hour or C-reactive protein =10 mg/L
within 6 weeks of baseline.

- Receiving or able to receive prednisone 20-60 mg/day for the treatment of active GCA.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Organ transplantation recipient (except corneas, unless it is within 3 months prior to
baseline visit).

- Major ischemic event, unrelated to GCA, within 12 weeks of screening.

- Any prior use of the following therapies, for the treatment of GCA:

- Janus kinase inhibitor (e.g., tofacitinib) within 4 weeks of baseline.

- Cell-depletion agents (e.g., anti CD20) without evidence of recovery of B cells to
baseline level.

- Abatacept within 8 weeks of baseline.

- Anakinra within 1 week of baseline.

- Tumor necrosis factor inhibitors within 2-8 weeks (etanercept within 2 weeks;
infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or less than at
least 5 half-lives have elapsed prior to baseline, whichever is longer.

- Therapeutic failure, including inadequate response or intolerance, or
contraindication, to biological IL-6/(R) antagonist (prior experience with IL-6/(R)
antagonist that was terminated for reasons unrelated to therapeutic failure at least 3
months before baseline is not exclusionary).

- Use of any alkylating agents including cyclophosphamide within 6 months of baseline.

- Use of immunosuppressant, such as hydroxychloroquine, cyclosporine, azathioprine,
mycophenolate mofetil or leflunomide within 4 weeks of baseline. (Use of methotrexate
(MTX) not exceeding 25 mg per week and have been stable for at least 3 months prior to
baseline is not exclusionary).

- Concurrent use of systemic corticosteroids (CS) for conditions other than GCA.

- Use of IV CS at a dose equivalent to 100 mg of methylprednisolone or higher within 8
weeks of baseline for GCA therapy.

- Pregnant or breastfeeding woman.

- Patients with active or untreated latent tuberculosis.

- Patients with history of invasive opportunistic infections.

- Patients with fever associated with infection or chronic, persistent or recurring
infections requiring active treatment.

- Patients with uncontrolled diabetes mellitus.

- Patients with non-healed or healing skin ulcers.

- Patients who received any live, attenuated vaccine within 3 months of baseline.

- Patients who are positive for hepatitis B, hepatitis C and/or HIV.

- Patients with a history of active or recurrent herpes zoster.

- Patients with a history of or prior articular or prosthetic joint infection.

- Prior or current history of malignancy.

- Patients who have had surgery within 4 weeks of screening or planned surgery during
study.

- Patients with a history of inflammatory bowel disease or severe diverticulitis or
previous gastrointestinal perforation..

The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360003 - Camberwell
Recruitment hospital [2] 0 0
Investigational Site Number 0360006 - Clayton
Recruitment hospital [3] 0 0
Investigational Site Number 0360008 - Geelong
Recruitment hospital [4] 0 0
Investigational Site Number 0360001 - Kogarah
Recruitment hospital [5] 0 0
Investigational Site Number 0360002 - Maroochydore
Recruitment hospital [6] 0 0
Investigational Site Number 0360005 - Murdoch
Recruitment hospital [7] 0 0
Investigational Site Number 0360007 - Woodville
Recruitment postcode(s) [1] 0 0
3124 - Camberwell
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
4558 - Maroochydore
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment postcode(s) [7] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Idaho
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Austria
State/province [13] 0 0
Innsbruck
Country [14] 0 0
Austria
State/province [14] 0 0
Wien
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Canada
State/province [16] 0 0
Hamilton
Country [17] 0 0
Canada
State/province [17] 0 0
Rimouski
Country [18] 0 0
Canada
State/province [18] 0 0
Sherbrooke
Country [19] 0 0
Canada
State/province [19] 0 0
Trois-Rivières
Country [20] 0 0
Croatia
State/province [20] 0 0
Zagreb
Country [21] 0 0
Denmark
State/province [21] 0 0
Aarhus C
Country [22] 0 0
Denmark
State/province [22] 0 0
Svendborg
Country [23] 0 0
Denmark
State/province [23] 0 0
Ålborg
Country [24] 0 0
France
State/province [24] 0 0
Brest
Country [25] 0 0
France
State/province [25] 0 0
Lille
Country [26] 0 0
France
State/province [26] 0 0
Montivilliers
Country [27] 0 0
France
State/province [27] 0 0
Montpellier
Country [28] 0 0
France
State/province [28] 0 0
Mulhouse
Country [29] 0 0
France
State/province [29] 0 0
Paris Cedex 13
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Pessac
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Kirchheim Unter Teck
Country [34] 0 0
Germany
State/province [34] 0 0
Tübingen
Country [35] 0 0
Hungary
State/province [35] 0 0
Debrecen
Country [36] 0 0
Israel
State/province [36] 0 0
Ashkelon
Country [37] 0 0
Israel
State/province [37] 0 0
Kfar Saba
Country [38] 0 0
Israel
State/province [38] 0 0
Petah-Tikva
Country [39] 0 0
Italy
State/province [39] 0 0
Milano
Country [40] 0 0
Italy
State/province [40] 0 0
Pisa
Country [41] 0 0
Italy
State/province [41] 0 0
Rozzano
Country [42] 0 0
Netherlands
State/province [42] 0 0
Den Haag
Country [43] 0 0
Netherlands
State/province [43] 0 0
Leeuwarden
Country [44] 0 0
Netherlands
State/province [44] 0 0
Rotterdam
Country [45] 0 0
Netherlands
State/province [45] 0 0
Sittard-Geleen
Country [46] 0 0
Netherlands
State/province [46] 0 0
Venlo
Country [47] 0 0
Portugal
State/province [47] 0 0
Almada
Country [48] 0 0
Portugal
State/province [48] 0 0
Aveiro
Country [49] 0 0
Portugal
State/province [49] 0 0
Lisboa
Country [50] 0 0
Portugal
State/province [50] 0 0
Ponte De Lima
Country [51] 0 0
Spain
State/province [51] 0 0
Bilbao
Country [52] 0 0
Spain
State/province [52] 0 0
Córdoba
Country [53] 0 0
Spain
State/province [53] 0 0
La Coruña
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Sabadell
Country [56] 0 0
Spain
State/province [56] 0 0
Santa Cruz De Tenerife
Country [57] 0 0
Sweden
State/province [57] 0 0
Uppsala
Country [58] 0 0
Sweden
State/province [58] 0 0
Örebro
Country [59] 0 0
Switzerland
State/province [59] 0 0
St. Gallen
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To evaluate the efficacy of sarilumab in patients with giant cell arteritis (GCA) as assessed
by the proportion of patients with sustained remission for sarilumab compared to placebo, in
combination with a corticosteroid (CS) tapering course.

Secondary Objective:

- To demonstrate the efficacy of sarilumab in patients with GCA compared to placebo, in
combination with CS taper with regards to:

- Clinical responses (such as responses based on disease remission rates, time to first
disease flare) over time.

- Cumulative CS (including prednisone) exposure.

- To assess the safety (including immunogenicity) and tolerability of sarilumab in
patients with GCA.

- To measure sarilumab serum concentrations in patients with GCA.

- To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by
glucocorticoid toxicity index (GTI).
Trial website
https://clinicaltrials.gov/show/NCT03600805
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03600805