Clinical trial NCT03600818: Evaluation of the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Polymyalgia Rheumatica
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-07-26
Enrollment: 118
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the efficacy of KEVZARA (sarilumab) in participants with polymyalgia rheumatica (PMR) as assessed by the proportion of participants 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 participants with PMR 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 participants with PMR.
* To measure sarilumab serum concentrations in participants with PMR.
* To assess the effect of sarilumab in reducing glucocorticoid toxicity as measured by the composite glucocorticoid toxicity index (GTI) questionnaire.

Detailed description: Study duration per participant was approximative 62 weeks including up to a 4-week screening period, 52-week treatment period and 6-week follow-up period.

Eligibility criteria: Inclusion criteria :

* Diagnosis of PMR according to European League Against Rheumatism/American College of Rheumatology classification criteria.
* Participants must be on prednisone of at least 7.5 milligrams per day (mg/day) (or equivalent) and not exceeding 20 mg/day at screening and during the screening period.
* Participant was willing and able to take prednisone of 15 mg/day at randomization.
* Participants had a history of being treated for at least 8 weeks with prednisone (greater than or equal to \[\>=\]10 mg/day or equivalent).
* Participants must have had at least one episode of unequivocal PMR flare while attempting to taper prednisone at a dose that was \>= 7.5 mg/day (or equivalent) within the past 12 Weeks prior to screening:

  * Unequivocal symptoms of PMR flare included shoulder and/or hip girdle pain associated with inflammatory stiffness.
* Participants had erythrocyte sedimentation rate \>=30 millimeters per hour (mm/hr) and/or C-reactive protein \>=10 milligrams per liter (mg/L) associated with PMR disease activity within 12 weeks prior to screening.

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 interleukin-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 was 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 greater than (\>) 15 mg/week within 3 months of Baseline
* Concurrent use of systemic CS for conditions other than PMR.
* 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 required 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 were positive for hepatitis B, hepatitis C and/or human immunodeficiency virus.
* 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.

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Remission at Week 52
timeFrame: At Week 52
Secondary outcomes:
measure: Total Cumulative Corticosteroid Dose
timeFrame: Up to Week 52
measure: Number of Participants Who Achieved Disease Remission up to Week 12
timeFrame: Up to Week 12
measure: Number of Participants With Absence of Disease Flare From Week 12 Through Week 52
timeFrame: From Week 12 Through Week 52
measure: Number of Participants With Sustained Reduction of CRP From Week 12 Through Week 52
timeFrame: From Week 12 through Week 52
measure: Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52
timeFrame: From Week 12 through Week 52
measure: Time to First Polymyalgia Rheumatica Flare After Clinical Remission up to Week 52
timeFrame: Up to Week 52
measure: Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 52
timeFrame: At Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose (i.e. Day 1) up to 60 days after last dose date of study drug (i.e. up to Week 60)
measure: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities During TEAE Period
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
measure: Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameter
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
measure: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
measure: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
measure: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
measure: Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
timeFrame: From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
measure: Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab
timeFrame: Pre-dose on Week 0 (Baseline), Week 2, 4, 12, 16, 24, and 52
measure: Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24
timeFrame: Post-dose at Week 24
Other outcomes:
Locations:
city: Upland
country: United States
facility: Investigational Site Number 8400003
state: California
city: Denver
country: United States
facility: Investigational Site Number 8400005
state: Colorado
city: Stamford
country: United States
facility: Investigational Site Number 8400009
state: Connecticut
city: Boca Raton
country: United States
facility: Investigational Site Number 8400002
state: Florida
city: Iowa City
country: United States
facility: Investigational Site Number 8400014
state: Iowa
city: Boston
country: United States
facility: Investigational Site Number 8400006
state: Massachusetts
city: New York
country: United States
facility: Investigational Site Number 8400022
state: New York
city: Dallas
country: United States
facility: Investigational Site Number 8400011
state: Texas
city: Lufkin
country: United States
facility: Investigational Site Number 8400025
state: Texas
city: Spokane
country: United States
facility: Investigational Site Number 8400015
state: Washington
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320005
city: Caba
country: Argentina
facility: Investigational Site Number 0320002
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number 0320003
city: Camberwell
country: Australia
facility: Investigational Site Number 0360003
city: Kogarah
country: Australia
facility: Investigational Site Number 0360001
city: Maroochydore
country: Australia
facility: Investigational Site Number 0360002
city: Woodville South
country: Australia
facility: Investigational Site Number 0360004
city: Gent
country: Belgium
facility: Investigational Site Number 0560003
city: Leuven
country: Belgium
facility: Investigational Site Number 0560001
city: Hamilton
country: Canada
facility: Investigational Site Number 1240007
city: Montreal
country: Canada
facility: Investigational Site Number 1240010
city: Rimouski
country: Canada
facility: Investigational Site Number 1240001
city: Sherbrooke
country: Canada
facility: Investigational Site Number 1240005
city: Trois-Rivières
country: Canada
facility: Investigational Site Number 1240003
city: Tallinn
country: Estonia
facility: Investigational Site Number 2330001
city: Brest Cedex
country: France
facility: Investigational Site Number 2500005
city: Caen Cedex 9
country: France
facility: Investigational Site Number 2500011
city: Le Kremlin Bicetre
country: France
facility: Investigational Site Number 2500015
city: Lille Cedex
country: France
facility: Investigational Site Number 2500010
city: Montivilliers
country: France
facility: Investigational Site Number 2500002
city: Montpellier
country: France
facility: Investigational Site Number 2500003
city: Paris
country: France
facility: Investigational Site Number 2500004
city: Pierre Benite Cedex
country: France
facility: Investigational Site Number 2500016
city: Toulouse Cedex 09
country: France
facility: Investigational Site Number 2500014
city: Bad Abbach
country: Germany
facility: Investigational Site Number 2760008
city: Berlin
country: Germany
facility: Investigational Site Number 2760009
city: Berlin
country: Germany
facility: Investigational Site Number 2760001
city: Dresden
country: Germany
facility: Investigational Site Number 2760002
city: Kirchheim Unter Teck
country: Germany
facility: Investigational Site Number 2760003
city: München
country: Germany
facility: Investigational Site Number 2760004
city: Tübingen
country: Germany
facility: Investigational Site Number 2760007
city: Debrecen
country: Hungary
facility: Investigational Site Number 3480001
city: Haifa
country: Israel
facility: Investigational Site Number 3760001
city: Haifa
country: Israel
facility: Investigational Site Number 3760004
city: Kfar Saba
country: Israel
facility: Investigational Site Number 3760003
city: Petah-Tikva
country: Israel
facility: Investigational Site Number 3760002
city: Tel Hashomer
country: Israel
facility: Investigational Site Number 3760005
city: Milano
country: Italy
facility: Investigational Site Number 3800003
city: Milano
country: Italy
facility: Investigational Site Number 3800001
city: Pisa
country: Italy
facility: Investigational Site Number 3800004
city: Reggio Emilia
country: Italy
facility: Investigational Site Number 3800002
city: Rozzano
country: Italy
facility: Investigational Site Number 3800005
city: Verona
country: Italy
facility: Investigational Site Number 3800008
city: Fuchu-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Kamakura-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Kawachinagano-Shi
country: Japan
facility: Investigational Site Number 3920005
city: Takasaki-Shi
country: Japan
facility: Investigational Site Number 3920001
city: Alkmaar
country: Netherlands
facility: Investigational Site Number 5280003
city: Almelo
country: Netherlands
facility: Investigational Site Number 5280002
city: Den Haag
country: Netherlands
facility: Investigational Site Number 5280007
city: Leeuwarden
country: Netherlands
facility: Investigational Site Number 5280005
city: Nijmegen
country: Netherlands
facility: Investigational Site Number 5280004
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 5280008
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430004
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430008
city: A Coruña / Santiago De Compostela
country: Spain
facility: Investigational Site Number 7240004
city: Badalona
country: Spain
facility: Investigational Site Number 7240005
city: Getafe
country: Spain
facility: Investigational Site Number 7240001
city: Granada
country: Spain
facility: Investigational Site Number 7240008
city: Madrid
country: Spain
facility: Investigational Site Number 7240002
city: Santander
country: Spain
facility: Investigational Site Number 7240006
city: Valencia
country: Spain
facility: Investigational Site Number 7240007
city: Bern
country: Switzerland
facility: Investigational Site Number 7560001
city: St. Gallen
country: Switzerland
facility: Investigational Site Number 7560002
city: Gateshead
country: United Kingdom
facility: Investigational Site Number 8260004
city: Leeds
country: United Kingdom
facility: Investigational Site Number 8260003
city: Manchester
country: United Kingdom
facility: Investigational Site Number 8260009
city: Newport
country: United Kingdom
facility: Investigational Site Number 8260007
city: Plymouth
country: United Kingdom
facility: Investigational Site Number 8260002
city: Southend
country: United Kingdom
facility: Investigational Site Number 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: