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Evaluation of the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica

Primary Purpose

Polymyalgia Rheumatica

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sarilumab SAR153191 (REGN88)
Sarilumab-matching placebo
Prednisone
Prednisone-matching placebo
Prednisone
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polymyalgia Rheumatica

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 8400003
  • Investigational Site Number 8400005
  • Investigational Site Number 8400009
  • Investigational Site Number 8400002
  • Investigational Site Number 8400014
  • Investigational Site Number 8400006
  • Investigational Site Number 8400022
  • Investigational Site Number 8400011
  • Investigational Site Number 8400025
  • Investigational Site Number 8400015
  • Investigational Site Number 0320001
  • Investigational Site Number 0320005
  • Investigational Site Number 0320002
  • Investigational Site Number 0320003
  • Investigational Site Number 0360003
  • Investigational Site Number 0360001
  • Investigational Site Number 0360002
  • Investigational Site Number 0360004
  • Investigational Site Number 0560003
  • Investigational Site Number 0560001
  • Investigational Site Number 1240007
  • Investigational Site Number 1240010
  • Investigational Site Number 1240001
  • Investigational Site Number 1240005
  • Investigational Site Number 1240003
  • Investigational Site Number 2330001
  • Investigational Site Number 2500005
  • Investigational Site Number 2500011
  • Investigational Site Number 2500015
  • Investigational Site Number 2500010
  • Investigational Site Number 2500002
  • Investigational Site Number 2500003
  • Investigational Site Number 2500004
  • Investigational Site Number 2500016
  • Investigational Site Number 2500014
  • Investigational Site Number 2760008
  • Investigational Site Number 2760009
  • Investigational Site Number 2760001
  • Investigational Site Number 2760002
  • Investigational Site Number 2760003
  • Investigational Site Number 2760004
  • Investigational Site Number 2760007
  • Investigational Site Number 3480001
  • Investigational Site Number 3760001
  • Investigational Site Number 3760004
  • Investigational Site Number 3760003
  • Investigational Site Number 3760002
  • Investigational Site Number 3760005
  • Investigational Site Number 3800003
  • Investigational Site Number 3800001
  • Investigational Site Number 3800004
  • Investigational Site Number 3800002
  • Investigational Site Number 3800005
  • Investigational Site Number 3800008
  • Investigational Site Number 3920002
  • Investigational Site Number 3920003
  • Investigational Site Number 3920005
  • Investigational Site Number 3920001
  • Investigational Site Number 5280003
  • Investigational Site Number 5280002
  • Investigational Site Number 5280007
  • Investigational Site Number 5280005
  • Investigational Site Number 5280004
  • Investigational Site Number 5280008
  • Investigational Site Number 6430002
  • Investigational Site Number 6430001
  • Investigational Site Number 6430003
  • Investigational Site Number 6430004
  • Investigational Site Number 6430008
  • Investigational Site Number 7240004
  • Investigational Site Number 7240005
  • Investigational Site Number 7240001
  • Investigational Site Number 7240008
  • Investigational Site Number 7240002
  • Investigational Site Number 7240006
  • Investigational Site Number 7240007
  • Investigational Site Number 7560001
  • Investigational Site Number 7560002
  • Investigational Site Number 8260004
  • Investigational Site Number 8260003
  • Investigational Site Number 8260009
  • Investigational Site Number 8260007
  • Investigational Site Number 8260002
  • Investigational Site Number 8260001

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo+52 Week Taper

Sarilumab 200mg q2w+14 Week Taper

Arm Description

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.

Participants received sarilumab 200 milligrams (mg) 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 14 weeks and prednisone-matching placebo from Week 14 up to Week 52.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Sustained Remission at Week 52
Sustained remission was defined as meeting all of the following parameters: achievement of disease remission (defined as resolution of signs and symptoms of polymyalgia rheumatica [PMR], and normalization of C-reactive protein [CRP] {less than [<]10 milligrams per liter [mg/L]}) not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active PMR plus an increase in corticosteroid [CS] dose due to PMR or elevation of erythrocyte sedimentation rate [ESR] attributable to active PMR plus an increase in CS dose due to PMR) from Week 12 through Week 52, sustained reduction of CRP (to <10 mg/L, with absence of successive elevations to greater than or equal to [>=]10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52.

Secondary Outcome Measures

Total Cumulative Corticosteroid Dose
Cumulative dose of CS used for PMR disease was defined as the dose taken up to the end of treatment, including expected prednisone in tapering regimen per protocol, add-on prednisone, CS used in rescue therapy and the use of commercial prednisone (an excess of <=100 mg of prednisone during the study treatment period). The total cumulative CS dose was based on the total number of days with complete or partial intake, no imputation was done on missed tablets.
Number of Participants Who Achieved Disease Remission up to Week 12
Disease remission was defined as resolution of signs and symptoms of PMR, and normalization of CRP (< 10 mg/L). The status of normalization of CRP (<10 mg/L) was determined based on the last two non-missing post-baseline CRP values measured up to Week 12. If at least one of the value was <10 mg/L, then it was considered as normalization of CRP. Participants who took rescue CS due to active PMR prior to Week 12 or who permanently withdrew from the study treatment prior to Week 12 were considered as not achieved disease remission by Week 12. During the initial 12 weeks of prednisone taper, treatment for one flare before Week 12 was permitted if it was successfully treated with a low dose (<=5 mg/day) prednisone add-on taper regimen (completed prior to Week 12) and provided that all other sustained remission parameters were met.
Number of Participants With Absence of Disease Flare From Week 12 Through Week 52
Disease flare was defined as either recurrence of signs and symptoms attributable to active PMR plus an increase in CS dose due to PMR, or elevation of ESR attributable to active PMR plus an increase in CS dose due to PMR.
Number of Participants With Sustained Reduction of CRP From Week 12 Through Week 52
Normalization (sustained reduction) of CRP was defined as CRP levels <10 mg/L. If there were two or more consecutive visits with CRP >=10 mg/L, then it was categorized as no normalization of CRP.
Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52
Successful adherence to the prednisone taper from Week 12 through Week 52 was defined as participants who did not take rescue therapy from Week 12 through Week 52 and any excess prednisone (beyond the per protocol CS tapering regimen) with a cumulative dose of <=100 mg (or equivalent), such as those employed to manage adverse event (AE) not related to PMR.
Time to First Polymyalgia Rheumatica Flare After Clinical Remission up to Week 52
Time to first PMR flare was defined as the duration (in days) from randomization to first PMR flare after clinical remission (defined as resolution of signs and symptoms and normalization of CRP [<10 mg/L]) and up to 52 weeks. Disease flare was defined as either the recurrence of signs or symptoms attributable to active plus an increase in CS dose due to PMR or elevation of ESR attributable to active PMR plus an increase in CS dose due to PMR. Kaplan-Meier method was used for the analysis. Participants who never achieved remission were censored at randomization day; and those who achieved clinical remission and never flared were censored at the end of treatment assessment date up to Week 52.
Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 52
GTI assessed glucocorticoid (GC) related morbidity and GC-sparing ability of other therapies; composed of 2 components: C-GTI and Specific List. C-GTI contained 9 domains and Specific List contained of 23 items (11 domains), used as complementary tool to C-GTI. C-GTI score was sum of 9 domain-specific scores at each visit and Cumulative GTI score was sum of C-GTI scores across each visit. Two cumulative GTI scores: CWS and AIS at Week 52 are reported in this outcome measure. CWS assessed cumulative GC toxicity regardless of whether toxicity had lasting effects or was transient. AIS assessed new therapy effectiveness in decreasing any Baseline GC toxicity over time. Negative scores reflect improvement in CS toxicities present from Baseline. For CWS, composite score ranged from 0 to 439 and for AIS, composite score ranged from -346 to 439. For both CWS and AIS, minimum score implies least toxicity and maximum score implies most toxicity.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product (IMP) to the last dose of the IMP +60 days).
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities During TEAE Period
Criteria for potentially clinically significant vital sign abnormalities: Systolic Blood Pressure (SBP): <= 95 mmHg and decrease from baseline (DFB) more than or equal to (>=) 20 mmHg; >= 160 mmHg and increase from baseline (IFB) >= 20 mmHg Diastolic blood pressure (DBP): <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg. Heart Rate (HR): <= 50 beats per min (bpm) and DFB >=20 bpm; >=120 bpm and IFB >= 20 bpm Weight: >=5% DFB; >=5% IFB. TEAE period was defined as the time from the first dose of the IMP to the last dose of the IMP + 60 days.
Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameter
Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): <= 115 grams per liter (g/L) (Male [M]), <= 95 g/L (Female [F]); >= 185 g/L (M), >= 165 g/L (F); DFB >= 20 g/L . Hematocrit: <= 0.37 volume/volume (v/v) (M); <= 0.32 v/v (F); >= 0.55 v/v (M); >= 0.5 v/v (F). Erythrocytes: >=6 Tera/ liter (L). Platelets: < 100 Giga/L, >= 700 Giga/L. Leukocytes: < 3.0 Giga/L (Non-Black [NB]); < 2.0 Giga/L (Black [B]), >= 16.0 Giga/L. Neutrophils: < 1.5 Giga/L (NB); < 1.0 Giga/L (B). Lymphocytes: > 4.0 Giga/L. Monocytes: > 0.7 Giga/L. Basophils: > 0.1 Giga/L. Eosinophils: > 0.5 Giga/L or > upper limit of normal (ULN) (if ULN >= 0.5 Giga/L).
Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters
Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 millimoles (mmol)/L and < lower limit of normal (LLN); >=11.1 mmol/L (unfasted [unfas]); >=7 mmol/L (fasted [fas]). HbA1c: >8%. Cholesterol: >=7.74 mmol/L. Triglycerides: >=4.6 mmol/L. C Reactive Protein (CRP): >2 ULN or >10 mg/L (if ULN not provided).
Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function
Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline. Creatinine clearance: >=60 to <90 milliliters per minute (mL/min); >=30 to <60 mL/min ; >=15 to <30 mL/min; <15 mL/min. Blood urea nitrogen: >=17 mmol/L. Urate: <120 micromol/L; >408 micromol/L.
Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function
Criteria for potentially clinically significant abnormalities: Albumin: <= 25 g/L. Alanine Aminotransferase (ALT): >3 ULN; >5 ULN; >10 ULN. Aspartate Aminotransferase (AST): >3 ULN; >5 ULN; >10 ULN; >20 ULN. Alkaline Phosphatase: >1.5 ULN. Bilirubin: >1.5 ULN; >2 ULN. ALT and Total Bilirubin: ALT > 3 ULN and Bilirubin > 2 ULN
Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
ADA response categories: 1) Treatment-boosted ADA positive participant: Participant with a positive ADA assay response at Baseline and with at least a 4-fold increase in titer compared to Baseline during TEAE period. 2) Treatment-emergent ADA positive participant: Participant with non-positive assay (meaning negative or missing) response at Baseline but with a positive assay response during the TEAE period (defined as the time from the first dose of the IMP to the last dose of the IMP +60 days).
Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab
Ctrough was pre dose concentration of drug. Data for this outcome measure was not planned to be collected and analyzed for placebo arm (Placebo+52 Week Taper) as pre-specified in the protocol.
Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24
Serum concentrations of functional sarilumab were analyzed using validated enzyme linked immunosorbent assay.

Full Information

First Posted
July 17, 2018
Last Updated
May 17, 2022
Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03600818
Brief Title
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

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Protracted recruitment timeline exacerbated by COVID-19 pandemic
Study Start Date
October 9, 2018 (Actual)
Primary Completion Date
May 19, 2021 (Actual)
Study Completion Date
May 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymyalgia Rheumatica

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo+52 Week Taper
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Sarilumab 200mg q2w+14 Week Taper
Arm Type
Experimental
Arm Description
Participants received sarilumab 200 milligrams (mg) 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 14 weeks and prednisone-matching placebo from Week 14 up to Week 52.
Intervention Type
Drug
Intervention Name(s)
Sarilumab SAR153191 (REGN88)
Intervention Description
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Sarilumab-matching placebo
Intervention Description
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration
Intervention Type
Drug
Intervention Name(s)
Prednisone-matching placebo
Intervention Description
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Pharmaceutical form:tablets Route of administration: oral administration
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving Sustained Remission at Week 52
Description
Sustained remission was defined as meeting all of the following parameters: achievement of disease remission (defined as resolution of signs and symptoms of polymyalgia rheumatica [PMR], and normalization of C-reactive protein [CRP] {less than [<]10 milligrams per liter [mg/L]}) not later than Week 12, absence of disease flare (defined as recurrence of signs and symptoms attributable to active PMR plus an increase in corticosteroid [CS] dose due to PMR or elevation of erythrocyte sedimentation rate [ESR] attributable to active PMR plus an increase in CS dose due to PMR) from Week 12 through Week 52, sustained reduction of CRP (to <10 mg/L, with absence of successive elevations to greater than or equal to [>=]10 mg/L) from Week 12 through Week 52, and successful adherence to prednisone taper from Week 12 through Week 52.
Time Frame
At Week 52
Secondary Outcome Measure Information:
Title
Total Cumulative Corticosteroid Dose
Description
Cumulative dose of CS used for PMR disease was defined as the dose taken up to the end of treatment, including expected prednisone in tapering regimen per protocol, add-on prednisone, CS used in rescue therapy and the use of commercial prednisone (an excess of <=100 mg of prednisone during the study treatment period). The total cumulative CS dose was based on the total number of days with complete or partial intake, no imputation was done on missed tablets.
Time Frame
Up to Week 52
Title
Number of Participants Who Achieved Disease Remission up to Week 12
Description
Disease remission was defined as resolution of signs and symptoms of PMR, and normalization of CRP (< 10 mg/L). The status of normalization of CRP (<10 mg/L) was determined based on the last two non-missing post-baseline CRP values measured up to Week 12. If at least one of the value was <10 mg/L, then it was considered as normalization of CRP. Participants who took rescue CS due to active PMR prior to Week 12 or who permanently withdrew from the study treatment prior to Week 12 were considered as not achieved disease remission by Week 12. During the initial 12 weeks of prednisone taper, treatment for one flare before Week 12 was permitted if it was successfully treated with a low dose (<=5 mg/day) prednisone add-on taper regimen (completed prior to Week 12) and provided that all other sustained remission parameters were met.
Time Frame
Up to Week 12
Title
Number of Participants With Absence of Disease Flare From Week 12 Through Week 52
Description
Disease flare was defined as either recurrence of signs and symptoms attributable to active PMR plus an increase in CS dose due to PMR, or elevation of ESR attributable to active PMR plus an increase in CS dose due to PMR.
Time Frame
From Week 12 Through Week 52
Title
Number of Participants With Sustained Reduction of CRP From Week 12 Through Week 52
Description
Normalization (sustained reduction) of CRP was defined as CRP levels <10 mg/L. If there were two or more consecutive visits with CRP >=10 mg/L, then it was categorized as no normalization of CRP.
Time Frame
From Week 12 through Week 52
Title
Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52
Description
Successful adherence to the prednisone taper from Week 12 through Week 52 was defined as participants who did not take rescue therapy from Week 12 through Week 52 and any excess prednisone (beyond the per protocol CS tapering regimen) with a cumulative dose of <=100 mg (or equivalent), such as those employed to manage adverse event (AE) not related to PMR.
Time Frame
From Week 12 through Week 52
Title
Time to First Polymyalgia Rheumatica Flare After Clinical Remission up to Week 52
Description
Time to first PMR flare was defined as the duration (in days) from randomization to first PMR flare after clinical remission (defined as resolution of signs and symptoms and normalization of CRP [<10 mg/L]) and up to 52 weeks. Disease flare was defined as either the recurrence of signs or symptoms attributable to active plus an increase in CS dose due to PMR or elevation of ESR attributable to active PMR plus an increase in CS dose due to PMR. Kaplan-Meier method was used for the analysis. Participants who never achieved remission were censored at randomization day; and those who achieved clinical remission and never flared were censored at the end of treatment assessment date up to Week 52.
Time Frame
Up to Week 52
Title
Composite Glucocorticoid Toxicity Index (C-GTI): Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 52
Description
GTI assessed glucocorticoid (GC) related morbidity and GC-sparing ability of other therapies; composed of 2 components: C-GTI and Specific List. C-GTI contained 9 domains and Specific List contained of 23 items (11 domains), used as complementary tool to C-GTI. C-GTI score was sum of 9 domain-specific scores at each visit and Cumulative GTI score was sum of C-GTI scores across each visit. Two cumulative GTI scores: CWS and AIS at Week 52 are reported in this outcome measure. CWS assessed cumulative GC toxicity regardless of whether toxicity had lasting effects or was transient. AIS assessed new therapy effectiveness in decreasing any Baseline GC toxicity over time. Negative scores reflect improvement in CS toxicities present from Baseline. For CWS, composite score ranged from 0 to 439 and for AIS, composite score ranged from -346 to 439. For both CWS and AIS, minimum score implies least toxicity and maximum score implies most toxicity.
Time Frame
At Week 52
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the time from the first dose of the investigational medicinal product (IMP) to the last dose of the IMP +60 days).
Time Frame
From first dose (i.e. Day 1) up to 60 days after last dose date of study drug (i.e. up to Week 60)
Title
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities During TEAE Period
Description
Criteria for potentially clinically significant vital sign abnormalities: Systolic Blood Pressure (SBP): <= 95 mmHg and decrease from baseline (DFB) more than or equal to (>=) 20 mmHg; >= 160 mmHg and increase from baseline (IFB) >= 20 mmHg Diastolic blood pressure (DBP): <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg. Heart Rate (HR): <= 50 beats per min (bpm) and DFB >=20 bpm; >=120 bpm and IFB >= 20 bpm Weight: >=5% DFB; >=5% IFB. TEAE period was defined as the time from the first dose of the IMP to the last dose of the IMP + 60 days.
Time Frame
From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
Title
Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameter
Description
Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): <= 115 grams per liter (g/L) (Male [M]), <= 95 g/L (Female [F]); >= 185 g/L (M), >= 165 g/L (F); DFB >= 20 g/L . Hematocrit: <= 0.37 volume/volume (v/v) (M); <= 0.32 v/v (F); >= 0.55 v/v (M); >= 0.5 v/v (F). Erythrocytes: >=6 Tera/ liter (L). Platelets: < 100 Giga/L, >= 700 Giga/L. Leukocytes: < 3.0 Giga/L (Non-Black [NB]); < 2.0 Giga/L (Black [B]), >= 16.0 Giga/L. Neutrophils: < 1.5 Giga/L (NB); < 1.0 Giga/L (B). Lymphocytes: > 4.0 Giga/L. Monocytes: > 0.7 Giga/L. Basophils: > 0.1 Giga/L. Eosinophils: > 0.5 Giga/L or > upper limit of normal (ULN) (if ULN >= 0.5 Giga/L).
Time Frame
From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
Title
Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters
Description
Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 millimoles (mmol)/L and < lower limit of normal (LLN); >=11.1 mmol/L (unfasted [unfas]); >=7 mmol/L (fasted [fas]). HbA1c: >8%. Cholesterol: >=7.74 mmol/L. Triglycerides: >=4.6 mmol/L. C Reactive Protein (CRP): >2 ULN or >10 mg/L (if ULN not provided).
Time Frame
From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
Title
Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function
Description
Criteria for potentially clinically significant abnormalities: Creatinine: >=150 micromol/L (adults); >=30% change from baseline, >=100% change from baseline. Creatinine clearance: >=60 to <90 milliliters per minute (mL/min); >=30 to <60 mL/min ; >=15 to <30 mL/min; <15 mL/min. Blood urea nitrogen: >=17 mmol/L. Urate: <120 micromol/L; >408 micromol/L.
Time Frame
From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
Title
Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function
Description
Criteria for potentially clinically significant abnormalities: Albumin: <= 25 g/L. Alanine Aminotransferase (ALT): >3 ULN; >5 ULN; >10 ULN. Aspartate Aminotransferase (AST): >3 ULN; >5 ULN; >10 ULN; >20 ULN. Alkaline Phosphatase: >1.5 ULN. Bilirubin: >1.5 ULN; >2 ULN. ALT and Total Bilirubin: ALT > 3 ULN and Bilirubin > 2 ULN
Time Frame
From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
Title
Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
Description
ADA response categories: 1) Treatment-boosted ADA positive participant: Participant with a positive ADA assay response at Baseline and with at least a 4-fold increase in titer compared to Baseline during TEAE period. 2) Treatment-emergent ADA positive participant: Participant with non-positive assay (meaning negative or missing) response at Baseline but with a positive assay response during the TEAE period (defined as the time from the first dose of the IMP to the last dose of the IMP +60 days).
Time Frame
From first dose (i.e., Day 1) up to 60 days after last dose date of study drug (i.e., up to Week 60)
Title
Pharmacokinetics (PK): Serum Trough Concentration (Ctrough) of Sarilumab
Description
Ctrough was pre dose concentration of drug. Data for this outcome measure was not planned to be collected and analyzed for placebo arm (Placebo+52 Week Taper) as pre-specified in the protocol.
Time Frame
Pre-dose on Week 0 (Baseline), Week 2, 4, 12, 16, 24, and 52
Title
Pharmacokinetics: Serum Drug Concentration of Sarilumab Post-dose at Week 24
Description
Serum concentrations of functional sarilumab were analyzed using validated enzyme linked immunosorbent assay.
Time Frame
Post-dose at Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400003
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Investigational Site Number 8400005
City
Denver
State/Province
Colorado
ZIP/Postal Code
80230
Country
United States
Facility Name
Investigational Site Number 8400009
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06905
Country
United States
Facility Name
Investigational Site Number 8400002
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Investigational Site Number 8400014
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Investigational Site Number 8400006
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Investigational Site Number 8400022
City
New York
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
Investigational Site Number 8400011
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Investigational Site Number 8400025
City
Lufkin
State/Province
Texas
ZIP/Postal Code
75904
Country
United States
Facility Name
Investigational Site Number 8400015
City
Spokane
State/Province
Washington
ZIP/Postal Code
99024
Country
United States
Facility Name
Investigational Site Number 0320001
City
Buenos Aires
ZIP/Postal Code
C1015ABO
Country
Argentina
Facility Name
Investigational Site Number 0320005
City
Buenos Aires
ZIP/Postal Code
C1121ABE
Country
Argentina
Facility Name
Investigational Site Number 0320002
City
Caba
ZIP/Postal Code
C1181ACH
Country
Argentina
Facility Name
Investigational Site Number 0320003
City
San Miguel de Tucuman
ZIP/Postal Code
T4000AXL
Country
Argentina
Facility Name
Investigational Site Number 0360003
City
Camberwell
ZIP/Postal Code
3124
Country
Australia
Facility Name
Investigational Site Number 0360001
City
Kogarah
ZIP/Postal Code
2217
Country
Australia
Facility Name
Investigational Site Number 0360002
City
Maroochydore
ZIP/Postal Code
4558
Country
Australia
Facility Name
Investigational Site Number 0360004
City
Woodville South
ZIP/Postal Code
5011
Country
Australia
Facility Name
Investigational Site Number 0560003
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Investigational Site Number 0560001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number 1240007
City
Hamilton
ZIP/Postal Code
L8N 1Y2
Country
Canada
Facility Name
Investigational Site Number 1240010
City
Montreal
ZIP/Postal Code
H4A 3T2
Country
Canada
Facility Name
Investigational Site Number 1240001
City
Rimouski
ZIP/Postal Code
G5L 5T1
Country
Canada
Facility Name
Investigational Site Number 1240005
City
Sherbrooke
ZIP/Postal Code
J1G 2E8
Country
Canada
Facility Name
Investigational Site Number 1240003
City
Trois-Rivières
ZIP/Postal Code
G8Z 1Y2
Country
Canada
Facility Name
Investigational Site Number 2330001
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Investigational Site Number 2500005
City
Brest Cedex
ZIP/Postal Code
29609
Country
France
Facility Name
Investigational Site Number 2500011
City
Caen Cedex 9
ZIP/Postal Code
14033
Country
France
Facility Name
Investigational Site Number 2500015
City
Le Kremlin Bicetre
ZIP/Postal Code
94270
Country
France
Facility Name
Investigational Site Number 2500010
City
Lille Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Investigational Site Number 2500002
City
Montivilliers
ZIP/Postal Code
76290
Country
France
Facility Name
Investigational Site Number 2500003
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Investigational Site Number 2500004
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Investigational Site Number 2500016
City
Pierre Benite Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
Investigational Site Number 2500014
City
Toulouse Cedex 09
ZIP/Postal Code
31059
Country
France
Facility Name
Investigational Site Number 2760008
City
Bad Abbach
ZIP/Postal Code
93077
Country
Germany
Facility Name
Investigational Site Number 2760009
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Investigational Site Number 2760001
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Investigational Site Number 2760002
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Investigational Site Number 2760003
City
Kirchheim Unter Teck
ZIP/Postal Code
73230
Country
Germany
Facility Name
Investigational Site Number 2760004
City
München
ZIP/Postal Code
80336
Country
Germany
Facility Name
Investigational Site Number 2760007
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Investigational Site Number 3480001
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Investigational Site Number 3760001
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Investigational Site Number 3760004
City
Haifa
ZIP/Postal Code
34362
Country
Israel
Facility Name
Investigational Site Number 3760003
City
Kfar Saba
ZIP/Postal Code
44281
Country
Israel
Facility Name
Investigational Site Number 3760002
City
Petah-Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Investigational Site Number 3760005
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Investigational Site Number 3800003
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Investigational Site Number 3800001
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Investigational Site Number 3800004
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Investigational Site Number 3800002
City
Reggio Emilia
ZIP/Postal Code
42100
Country
Italy
Facility Name
Investigational Site Number 3800005
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Investigational Site Number 3800008
City
Verona
ZIP/Postal Code
37134
Country
Italy
Facility Name
Investigational Site Number 3920002
City
Fuchu-Shi
Country
Japan
Facility Name
Investigational Site Number 3920003
City
Kamakura-Shi
Country
Japan
Facility Name
Investigational Site Number 3920005
City
Kawachinagano-Shi
Country
Japan
Facility Name
Investigational Site Number 3920001
City
Takasaki-Shi
Country
Japan
Facility Name
Investigational Site Number 5280003
City
Alkmaar
ZIP/Postal Code
1815 JD
Country
Netherlands
Facility Name
Investigational Site Number 5280002
City
Almelo
ZIP/Postal Code
7609 PP
Country
Netherlands
Facility Name
Investigational Site Number 5280007
City
Den Haag
ZIP/Postal Code
2545 CH
Country
Netherlands
Facility Name
Investigational Site Number 5280005
City
Leeuwarden
ZIP/Postal Code
8934 AD
Country
Netherlands
Facility Name
Investigational Site Number 5280004
City
Nijmegen
ZIP/Postal Code
6522 JV
Country
Netherlands
Facility Name
Investigational Site Number 5280008
City
Rotterdam
ZIP/Postal Code
3079
Country
Netherlands
Facility Name
Investigational Site Number 6430002
City
Moscow
ZIP/Postal Code
115404
Country
Russian Federation
Facility Name
Investigational Site Number 6430001
City
Moscow
ZIP/Postal Code
121374
Country
Russian Federation
Facility Name
Investigational Site Number 6430003
City
Moscow
ZIP/Postal Code
123182
Country
Russian Federation
Facility Name
Investigational Site Number 6430004
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
Facility Name
Investigational Site Number 6430008
City
Saint-Petersburg
ZIP/Postal Code
192242
Country
Russian Federation
Facility Name
Investigational Site Number 7240004
City
A Coruña / Santiago De Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Investigational Site Number 7240005
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Investigational Site Number 7240001
City
Getafe
ZIP/Postal Code
28905
Country
Spain
Facility Name
Investigational Site Number 7240008
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
Investigational Site Number 7240002
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Investigational Site Number 7240006
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Investigational Site Number 7240007
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Investigational Site Number 7560001
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Investigational Site Number 7560002
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Investigational Site Number 8260004
City
Gateshead
ZIP/Postal Code
NE9 6SX
Country
United Kingdom
Facility Name
Investigational Site Number 8260003
City
Leeds
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
Facility Name
Investigational Site Number 8260009
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
Facility Name
Investigational Site Number 8260007
City
Newport
ZIP/Postal Code
PO30 5TG
Country
United Kingdom
Facility Name
Investigational Site Number 8260002
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Investigational Site Number 8260001
City
Southend
ZIP/Postal Code
SS0 0RY
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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
IPD Sharing URL
https://vivli.org

Learn more about this trial

Evaluation of the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica

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