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

NCT03600818 | Terminated Phase 3 Results FDA Drug

• 3 other identifiers: EFC151602017-002989-42U1111-1201-0777
• Study Type: interventional
• Target: 118
• Locations: 16 countries
• Sites: 83

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.

Conditions

Polymyalgia Rheumatica

Outcome Measures

Primary Outcomes (1)

• 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.

  At Week 52

Secondary Outcomes (16)

• Total Cumulative Corticosteroid Dose

  Up to Week 52

• Number of Participants Who Achieved Disease Remission up to Week 12

  Up to Week 12

• Number of Participants With Absence of Disease Flare From Week 12 Through Week 52

  From Week 12 Through Week 52

• Number of Participants With Sustained Reduction of CRP From Week 12 Through Week 52

  From Week 12 through Week 52

• Number of Participants With Successful Adherence to the Prednisone Taper From Week 12 Through Week 52

  From Week 12 through Week 52

Study Arms (2)

Placebo+52 Week Taper

PLACEBO COMPARATOR

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.

Drug: Sarilumab-matching placebo; Drug: Prednisone; Drug: Prednisone-matching placebo

Sarilumab 200mg q2w+14 Week Taper

EXPERIMENTAL

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.

Drug: Sarilumab SAR153191 (REGN88); Drug: Prednisone; Drug: Prednisone-matching placebo

Interventions

Sarilumab SAR153191 (REGN88) DRUG

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Sarilumab 200mg q2w+14 Week Taper

Sarilumab-matching placebo DRUG

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Placebo+52 Week Taper

Prednisone DRUG

Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Placebo+52 Week Taper; Sarilumab 200mg q2w+14 Week Taper

Prednisone-matching placebo DRUG

Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Placebo+52 Week Taper; Sarilumab 200mg q2w+14 Week Taper

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (84)

Investigational Site Number 8400003

Upland, California, 91786, United States

Location

Investigational Site Number 8400005

Denver, Colorado, 80230, United States

Location

Investigational Site Number 8400009

Stamford, Connecticut, 06905, United States

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Investigational Site Number 8400002

Boca Raton, Florida, 33486, United States

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Investigational Site Number 8400014

Iowa City, Iowa, 52242, United States

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Investigational Site Number 8400006

Boston, Massachusetts, 02114, United States

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Investigational Site Number 8400022

New York, New York, 11201, United States

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Investigational Site Number 8400011

Dallas, Texas, 75231, United States

Location

Investigational Site Number 8400025

Lufkin, Texas, 75904, United States

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Investigational Site Number 8400015

Spokane, Washington, 99024, United States

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Investigational Site Number 0320001

Buenos Aires, C1015ABO, Argentina

Location

Investigational Site Number 0320005

Buenos Aires, C1121ABE, Argentina

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Investigational Site Number 0320002

Caba, C1181ACH, Argentina

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Investigational Site Number 0320003

San Miguel de Tucumán, T4000AXL, Argentina

Location

Investigational Site Number 0360003

Camberwell, 3124, Australia

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Investigational Site Number 0360001

Kogarah, 2217, Australia

Location

Investigational Site Number 0360002

Maroochydore, 4558, Australia

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Investigational Site Number 0360004

Woodville South, 5011, Australia

Location

Investigational Site Number 0560003

Ghent, 9000, Belgium

Location

Investigational Site Number 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number 1240007

Hamilton, L8N 1Y2, Canada

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Investigational Site Number 1240010

Montreal, H4A 3T2, Canada

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Investigational Site Number 1240001

Rimouski, G5L 5T1, Canada

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Investigational Site Number 1240005

Sherbrooke, J1G 2E8, Canada

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Investigational Site Number 1240003

Trois-Rivières, G8Z 1Y2, Canada

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Investigational Site Number 2330001

Tallinn, 13419, Estonia

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Investigational Site Number 2500005

Brest, 29609, France

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Investigational Site Number 2500011

Caen, 14033, France

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Investigational Site Number 2500015

Le Kremlin-Bicêtre, 94270, France

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Investigational Site Number 2500010

Lille, 59037, France

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Investigational Site Number 2500002

Montivilliers, 76290, France

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Investigational Site Number 2500003

Montpellier, 34295, France

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Investigational Site Number 2500004

Paris, 75013, France

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Investigational Site Number 2500016

Pierre-Bénite, 69495, France

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Investigational Site Number 2500014

Toulouse, 31059, France

Location

Investigational Site Number 2760008

Bad Abbach, 93077, Germany

Location

Investigational Site Number 2760009

Berlin, 10117, Germany

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Investigational Site Number 2760001

Berlin, 13125, Germany

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Investigational Site Number 2760002

Dresden, 01307, Germany

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Investigational Site Number 2760003

Kirchheim unter Teck, 73230, Germany

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Investigational Site Number 2760004

München, 80336, Germany

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Investigational Site Number 2760007

Tübingen, 72076, Germany

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Investigational Site Number 3480001

Debrecen, 4032, Hungary

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Investigational Site Number 3760001

Haifa, 31096, Israel

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Investigational Site Number 3760004

Haifa, 34362, Israel

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Investigational Site Number 3760003

Kfar Saba, 44281, Israel

Location

Investigational Site Number 3760002

Petah Tikva, 49100, Israel

Location

Investigational Site Number 3760005

Tel Litwinsky, 52621, Israel

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Investigational Site Number 3800003

Milan, 20122, Italy

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Investigational Site Number 3800001

Milan, 20132, Italy

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Investigational Site Number 3800004

Pisa, 56126, Italy

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Investigational Site Number 3800002

Reggio Emilia, 42100, Italy

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Investigational Site Number 3800005

Rozzano, 20089, Italy

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Investigational Site Number 3800008

Verona, 37134, Italy

Location

Investigational Site Number 3920002

Fuchu-Shi, Japan

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Investigational Site Number 3920003

Kamakura-Shi, Japan

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Investigational Site Number 3920005

Kawachinagano-Shi, Japan

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Investigational Site Number 3920001

Takasaki-Shi, Japan

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Investigational Site Number 5280003

Alkmaar, 1815 JD, Netherlands

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Investigational Site Number 5280002

Almelo, 7609 PP, Netherlands

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Investigational Site Number 5280005

Leeuwarden, 8934 AD, Netherlands

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Investigational Site Number 5280004

Nijmegen, 6522 JV, Netherlands

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Investigational Site Number 5280008

Rotterdam, 3079, Netherlands

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Investigational Site Number 5280007

The Hague, 2545 CH, Netherlands

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Investigational Site Number 6430002

Moscow, 115404, Russia

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Investigational Site Number 6430001

Moscow, 121374, Russia

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Investigational Site Number 6430003

Moscow, 123182, Russia

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Investigational Site Number 6430004

Moscow, 129110, Russia

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Investigational Site Number 6430008

Saint Petersburg, 192242, Russia

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Investigational Site Number 7240004

A Coruña / Santiago de Compostela, 15706, Spain

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Investigational Site Number 7240005

Badalona, 08916, Spain

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Investigational Site Number 7240001

Getafe, 28905, Spain

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Investigational Site Number 7240008

Granada, 18014, Spain

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Investigational Site Number 7240002

Madrid, 28041, Spain

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Investigational Site Number 7240006

Santander, 39008, Spain

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Investigational Site Number 7240007

Valencia, 46026, Spain

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Investigational Site Number 7560001

Bern, 3010, Switzerland

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Investigational Site Number 7560002

Sankt Gallen, 9007, Switzerland

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Investigational Site Number 8260004

Gateshead, NE9 6SX, United Kingdom

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Investigational Site Number 8260003

Leeds, LS7 4SA, United Kingdom

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Investigational Site Number 8260009

Manchester, M23 9LT, United Kingdom

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Investigational Site Number 8260007

Newport, PO30 5TG, United Kingdom

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Investigational Site Number 8260002

Plymouth, PL6 8DH, United Kingdom

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Investigational Site Number 8260001

Southend, SS0 0RY, United Kingdom

Location

Related Publications (2)

• Strand V, Msihid J, Sloane J, Nivens MC, Chao J, Giannelou A, Fiore S, Araujo L, Dasgupta B. Sarilumab in relapsing polymyalgia rheumatica: patient-reported outcomes from a phase 3, double-blind, randomised controlled trial. Lancet Rheumatol. 2025 Aug;7(8):e544-e553. doi: 10.1016/S2665-9913(25)00041-4. Epub 2025 Jun 19.

  PMID: 40544861 DERIVED

• Spiera RF, Unizony S, Warrington KJ, Sloane J, Giannelou A, Nivens MC, Akinlade B, Wong W, Bhore R, Lin Y, Buttgereit F, Devauchelle-Pensec V, Rubbert-Roth A, Yancopoulos GD, Marrache F, Patel N, Dasgupta B; SAPHYR Investigators. Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper. N Engl J Med. 2023 Oct 5;389(14):1263-1272. doi: 10.1056/NEJMoa2303452.

  PMID: 37792612 DERIVED

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

sarilumab; Prednisone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Protracted recruitment timeline exacerbated by COVID-19 pandemic led to pre-mature termination of study, resulting in a change in the total expected number of participants and change in the statistical significance level.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: October 9, 2018
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: June 10, 2022
• Results First Posted: June 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); US (10); IL (5); IT (6); GB (6); BE (2); JP (4); ES (7); DE (7); CA (5); CH (2); AU (4); FR (9); AR (4); NL (6); RU (5)