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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03600805




Registration number
NCT03600805
Ethics application status
Date submitted
17/07/2018
Date registered
26/07/2018
Date last updated
28/03/2022

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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/11/2020
Sample size
Target
Accrual to date
Final
83
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
Primary Objective:

To evaluate the efficacy of sarilumab in participants with giant cell arteritis (GCA) as
assessed by the proportion of participants 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 participants 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
participants with GCA.

- To measure sarilumab serum concentrations in participants with GCA.

- To assess the effect of sarilumab on sparing glucocorticoid toxicity as measured by
glucocorticoid toxicity index (GTI).
Trial website
https://clinicaltrials.gov/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03600805