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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03600805
Ethics application status
Date submitted
17/07/2018
Date registered
26/07/2018

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
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
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

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: Placebo+52 Week Taper - Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.

Experimental: Placebo+26 Week Taper - Participants received sarilumab-matching placebo as SC injection q2w up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.

Placebo comparator: Sarilumab 150mg q2w+26 Week Taper - Participants received sarilumab 150 milligrams (mg) as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.

Placebo comparator: Sarilumab 200mg q2w+26 Week Taper - Participants received sarilumab 200 mg as SC injection q2w up to 52 weeks along with prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 26 weeks and prednisone-matching placebo from Week 26 up to Week 52.


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
Percentage of Participants Who Achieved Sustained Disease Remission at Week 52
Timepoint [1] 0 0
At Week 52
Primary outcome [2] 0 0
Percentage of Participants Who Achieved Sustained Disease Remission at Week 24
Timepoint [2] 0 0
At Week 24
Secondary outcome [1] 0 0
Number of Participants With Achievement of Disease Remission up to Week 12: Week 52 Analysis Set
Timepoint [1] 0 0
Up to Week 12
Secondary outcome [2] 0 0
Number of Participants With Achievement of Disease Remission up to Week 12: Intent-to-treat (ITT) Population
Timepoint [2] 0 0
Up to Week 12
Secondary outcome [3] 0 0
Number of Participants With Absence of Disease Flare From Week 12 Through Week 52: Week 52 Analysis Set
Timepoint [3] 0 0
From Week 12 through Week 52
Secondary outcome [4] 0 0
Number of Participants With Absence of Disease Flare From Week 12 Through Week 24: ITT Population
Timepoint [4] 0 0
From Week 12 through Week 24
Secondary outcome [5] 0 0
Number of Participants With Normalization of C-Reactive Protein From Week 12 Through Week 52: Week 52 Analysis Set
Timepoint [5] 0 0
From Week 12 through Week 52
Secondary outcome [6] 0 0
Number of Participants With Normalization of C-Reactive Protein (CRP) From Week 12 Through Week 24: ITT Population
Timepoint [6] 0 0
From Week 12 through Week 24
Secondary outcome [7] 0 0
Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52: Week 52 Analysis Set
Timepoint [7] 0 0
From Week 12 through Week 52
Secondary outcome [8] 0 0
Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 24: ITT Population
Timepoint [8] 0 0
From Week 12 through Week 24
Secondary outcome [9] 0 0
Total Cumulative Corticosteroid (Including Prednisone) Dose
Timepoint [9] 0 0
Up to Week 52
Secondary outcome [10] 0 0
Time to First Giant Cell Arteritis Disease Flare
Timepoint [10] 0 0
Up to Week 52
Secondary outcome [11] 0 0
Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 24: ITT Population
Timepoint [11] 0 0
At Week 24
Secondary outcome [12] 0 0
Composite Glucocorticoid Toxicity Index: Cumulative Worsening Score and Aggregate Improvement Score at Week 52
Timepoint [12] 0 0
At Week 52
Secondary outcome [13] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [13] 0 0
From first dose (i.e., Day 1) up to 60 days after last dose (i.e., up to Week 60)
Secondary outcome [14] 0 0
Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab
Timepoint [14] 0 0
Pre-dose on Week 0 (Baseline), Weeks 2, 4, 12, 16, 24 and 52
Secondary outcome [15] 0 0
Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24
Timepoint [15] 0 0
post-dose at Week 24
Secondary outcome [16] 0 0
Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
Timepoint [16] 0 0
From Day 1 (Baseline) up to last dose date of study drug + 60 days (i.e., up to Week 60)
Secondary outcome [17] 0 0
Pharmacodynamics: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
Timepoint [17] 0 0
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
Secondary outcome [18] 0 0
Pharmacodynamics: Change From Baseline in C-reactive Protein (CRP) Level at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
Timepoint [18] 0 0
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 52
Secondary outcome [19] 0 0
Pharmacodynamics: Change From Baseline in Interleukin-6 (IL-6) at Weeks 2, 12, 24, and 52
Timepoint [19] 0 0
Baseline, Weeks 2, 12, 24, and 52
Secondary outcome [20] 0 0
Pharmacodynamics: Change From Baseline in Soluble Interleukin-6 Receptor (sIL-6R) Level at Weeks 2, 12, 24, and 52
Timepoint [20] 0 0
Baseline, Weeks 2, 12, 24, and 52

Eligibility
Key inclusion criteria
Inclusion criteria :

* Diagnosis of 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 greater than or equal to (>=) 30 millimeter per hour or C-reactive protein >=10 mg per liter within 6 weeks of baseline.
* Received or were able to receive prednisone 20-60 mg/day for the treatment of active GCA.
Minimum age
50 Years
Maximum age
No limit
Sex
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 had elapsed prior to baseline, whichever was longer.
* Therapeutic failure, including inadequate response or intolerance, or contraindication, to biological Interleukin 6 (IL-6) 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 was 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 had been stable for at least 3 months prior to baseline was not exclusionary).
* Concurrent use of systemic CS for conditions other than GCA.
* Use of intervascular CS at a dose equivalent to 100 mg of methylprednisolone or higher within 8 weeks of baseline for GCA therapy.
* Pregnant or breastfeeding woman.
* Participants with active or untreated latent tuberculosis.
* Participants with history of invasive opportunistic infections.
* Participants with fever associated with infection or chronic, persistent or recurring infections requiring active treatment.
* Participants with uncontrolled diabetes mellitus.
* Participants with non-healed or healing skin ulcers.
* Participants who received any live, attenuated vaccine within 3 months of baseline.
* Participants who are positive for hepatitis B, hepatitis C and/or HIV.
* Participants with a history of active or recurrent herpes zoster.
* Participants with a history of or prior articular or prosthetic joint infection.
* Prior or current history of malignancy.
* Participants who have had surgery within 4 weeks of screening or planned surgery during study.
* Participants with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation..

The above information was not intended to contain all considerations relevant to a participant'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
Stopped early
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 0360001 - Kogarah
Recruitment postcode(s) [1] 0 0
3124 - Camberwell
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
Oregon
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Caba
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Canada
State/province [9] 0 0
Hamilton
Country [10] 0 0
Canada
State/province [10] 0 0
Montreal
Country [11] 0 0
Canada
State/province [11] 0 0
Rimouski
Country [12] 0 0
Canada
State/province [12] 0 0
Sherbrooke
Country [13] 0 0
Canada
State/province [13] 0 0
Trois-Rivières
Country [14] 0 0
Croatia
State/province [14] 0 0
Zagreb
Country [15] 0 0
Denmark
State/province [15] 0 0
Aarhus C
Country [16] 0 0
Denmark
State/province [16] 0 0
Svendborg
Country [17] 0 0
Estonia
State/province [17] 0 0
Tallinn
Country [18] 0 0
France
State/province [18] 0 0
Brest Cedex
Country [19] 0 0
France
State/province [19] 0 0
Montivilliers
Country [20] 0 0
France
State/province [20] 0 0
Montpellier
Country [21] 0 0
France
State/province [21] 0 0
Mulhouse
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
France
State/province [23] 0 0
Pessac
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Dresden
Country [26] 0 0
Germany
State/province [26] 0 0
Kirchheim Unter Teck
Country [27] 0 0
Germany
State/province [27] 0 0
München
Country [28] 0 0
Germany
State/province [28] 0 0
Tübingen
Country [29] 0 0
Hungary
State/province [29] 0 0
Debrecen
Country [30] 0 0
Israel
State/province [30] 0 0
Ashkelon
Country [31] 0 0
Israel
State/province [31] 0 0
Haifa
Country [32] 0 0
Italy
State/province [32] 0 0
Milano
Country [33] 0 0
Italy
State/province [33] 0 0
Rozzano
Country [34] 0 0
Netherlands
State/province [34] 0 0
Den Haag
Country [35] 0 0
Netherlands
State/province [35] 0 0
Leeuwarden
Country [36] 0 0
Netherlands
State/province [36] 0 0
Sittard-Geleen
Country [37] 0 0
Netherlands
State/province [37] 0 0
Venlo
Country [38] 0 0
Portugal
State/province [38] 0 0
Almada
Country [39] 0 0
Portugal
State/province [39] 0 0
Aveiro
Country [40] 0 0
Portugal
State/province [40] 0 0
Ponte De Lima
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Kemerovo
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Moscow
Country [43] 0 0
Slovenia
State/province [43] 0 0
Ljubljana
Country [44] 0 0
Spain
State/province [44] 0 0
Bilbao
Country [45] 0 0
Spain
State/province [45] 0 0
La Coruña
Country [46] 0 0
Spain
State/province [46] 0 0
Madrid
Country [47] 0 0
Spain
State/province [47] 0 0
Sabadell
Country [48] 0 0
Spain
State/province [48] 0 0
Santa Cruz De Tenerife
Country [49] 0 0
Sweden
State/province [49] 0 0
Uppsala
Country [50] 0 0
Sweden
State/province [50] 0 0
Örebro
Country [51] 0 0
Switzerland
State/province [51] 0 0
St. Gallen
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Aberdeen
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Gateshead
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Leeds
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Manchester
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Portsmouth

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
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.