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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03600818




Registration number
NCT03600818
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 the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Scientific title
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Secondary ID [1] 0 0
2017-002989-42
Secondary ID [2] 0 0
EFC15160
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polymyalgia Rheumatica 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 (REGN88)
Treatment: Drugs - Sarilumab-matching placebo
Treatment: Drugs - Prednisone
Treatment: Drugs - Prednisone-matching placebo
Treatment: Drugs - Prednisone

Experimental: Group 1 - Sarilumab once every 2 weeks plus prednisone taper regimen of 14 weeks

Placebo Comparator: Group 2 - Placebo matching sarilumab once every 2 weeks plus prednisone taper regimen of 52 weeks


Treatment: Drugs: Sarilumab SAR153191 (REGN88)
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:over-encapsulated tablets Route of administration: oral administration

Treatment: Drugs: Prednisone-matching placebo
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Treatment: Drugs: Prednisone
Pharmaceutical form:tablets 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 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 polymyalgia rheumatica (PMR) flare - Duration of first PMR 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 58
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 polymyalgia rheumatica (PMR) according to European League Against
Rheumatism/American College of Rheumatology classification criteria.

- Patients must be on prednisone of at least 7.5 mg/day (or equivalent) and not
exceeding 20 mg/day at screening and during the screening period.

- Patient is willing and able to take prednisone of 15 mg/day at randomization.

- Patients must have a history of being treated for at least 8 weeks with prednisone
(=10 mg/day or equivalent).

- Patient must have had at least one episode of unequivocal PMR flare while attempting
to taper prednisone at a dose that is =7.5 mg/day (or equivalent) within the past 12
Weeks prior to screening:

- Unequivocal symptoms of PMR flare include shoulder and/or hip girdle pain associated
with inflammatory stiffness.

- Patients must have erythrocyte sedimentation rate =30 mm/hr and/or C-reactive protein
=10 mg/L associated with PMR disease activity within 12 weeks prior to screening.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Diagnosis of giant cell arteritis (e.g., persistent or recurrent localized headache,
temporal artery or scalp tenderness, jaw claudication, extremity claudication, blurry
or loss of vision, symptoms of stroke).

- Diagnosis of active fibromyalgia.

- Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective
tissue diseases, such as but not limited to systemic lupus erythematosus, systemic
sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing
spondylitis.

- Concurrent diagnosis of rhabdomyolysis or neuropathic muscular diseases.

- Inadequately treated hypothyroidism.

- Organ transplant recipient.

- Therapeutic failure including inadequate response or intolerance, or contraindication,
to biological IL-6 antagonist.

- Any prior (within the defined period below) or concurrent use of immunosuppressive
therapies but not limited to any of the following:

- Janus kinase inhibitor within 4 weeks of baseline.

- Alkylating agents including cyclophosphamide within 6 months of baseline.

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

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

- Abatacept within 8 weeks of baseline.

- Anakinra within 1 week of baseline.

- Cyclosporine, azathioprine or mycophenolate mofetil or leflunomide within 4 weeks of
baseline.

- Unstable methotrexate (MTX) dose and/or MTX dose >15mg/week within 3 months of
baseline

- Concurrent use of systemic CS for conditions other than PMR.

- 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 0360001 - Kogarah
Recruitment hospital [3] 0 0
Investigational Site Number 0360002 - Maroochydore
Recruitment hospital [4] 0 0
Investigational Site Number 0360004 - Woodville South
Recruitment postcode(s) [1] 0 0
3124 - Camberwell
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
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
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Argentina
State/province [12] 0 0
Buenos Aires
Country [13] 0 0
Argentina
State/province [13] 0 0
San Miguel de Tucuman
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Belgium
State/province [16] 0 0
Liège
Country [17] 0 0
Canada
State/province [17] 0 0
Rimouski
Country [18] 0 0
Canada
State/province [18] 0 0
Saskatoon
Country [19] 0 0
Canada
State/province [19] 0 0
Sherbrooke
Country [20] 0 0
Canada
State/province [20] 0 0
Trois-Rivières
Country [21] 0 0
Estonia
State/province [21] 0 0
Tallinn
Country [22] 0 0
France
State/province [22] 0 0
Caen Cedex 9
Country [23] 0 0
France
State/province [23] 0 0
Le Kremlin Bicetre
Country [24] 0 0
France
State/province [24] 0 0
Lille Cedex
Country [25] 0 0
France
State/province [25] 0 0
Montivilliers
Country [26] 0 0
France
State/province [26] 0 0
Montpellier
Country [27] 0 0
France
State/province [27] 0 0
Paris Cedex 13
Country [28] 0 0
France
State/province [28] 0 0
Pierre Benite
Country [29] 0 0
France
State/province [29] 0 0
Toulouse Cedex 09
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Kirchheim Unter Teck
Country [32] 0 0
Hungary
State/province [32] 0 0
Debrecen
Country [33] 0 0
Israel
State/province [33] 0 0
Haifa
Country [34] 0 0
Israel
State/province [34] 0 0
Petah-Tikva
Country [35] 0 0
Israel
State/province [35] 0 0
Tel Hashomer
Country [36] 0 0
Italy
State/province [36] 0 0
Milano
Country [37] 0 0
Italy
State/province [37] 0 0
Pisa
Country [38] 0 0
Italy
State/province [38] 0 0
Reggio Emilia
Country [39] 0 0
Italy
State/province [39] 0 0
Rozzano
Country [40] 0 0
Italy
State/province [40] 0 0
Verona
Country [41] 0 0
Netherlands
State/province [41] 0 0
Alkmaar
Country [42] 0 0
Netherlands
State/province [42] 0 0
Almelo
Country [43] 0 0
Netherlands
State/province [43] 0 0
Den Haag
Country [44] 0 0
Netherlands
State/province [44] 0 0
Leeuwarden
Country [45] 0 0
Netherlands
State/province [45] 0 0
Nijmegen
Country [46] 0 0
Netherlands
State/province [46] 0 0
Rotterdam
Country [47] 0 0
Spain
State/province [47] 0 0
Badalona
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Spain
State/province [49] 0 0
Santander
Country [50] 0 0
Spain
State/province [50] 0 0
Santiago De Compostela
Country [51] 0 0
Spain
State/province [51] 0 0
Valencia
Country [52] 0 0
Switzerland
State/province [52] 0 0
St. Gallen
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Newport
Country [54] 0 0
United Kingdom
State/province [54] 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 KEVZARA (sarilumab) in patients with polymyalgia rheumatica (PMR)
as assessed by the proportion of subjects with sustained remission for sarilumab with a
shorter corticosteroid (CS) tapering regimen as compared to placebo with a longer CS tapering
regimen.

Secondary Objectives:

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

- Clinical responses (such as components of sustained remission, 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 PMR.

- To measure sarilumab serum concentrations in patients with PMR.

- To assess the effect of sarilumab in reducing glucocorticoid toxicity as measured by the
composite glucocorticoid toxicity index (GTI) questionnaire.
Trial website
https://clinicaltrials.gov/show/NCT03600818
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/NCT03600818