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

NCT ID: NCT03600818

Last Updated: 2022-06-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-09
• Study Completion Date: 2021-05-19

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.

Conditions

Polymyalgia Rheumatica

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo+52 Week Taper

Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.

Group Type: PLACEBO_COMPARATOR

Sarilumab-matching placebo

Intervention Type: DRUG

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Prednisone

Intervention Type: DRUG

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

Prednisone-matching placebo

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

Pharmaceutical form:tablets Route of administration: oral administration

Sarilumab 200mg q2w+14 Week Taper

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.

Group Type: EXPERIMENTAL

Sarilumab SAR153191 (REGN88)

Intervention Type: DRUG

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Prednisone

Intervention Type: DRUG

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

Prednisone-matching placebo

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

Pharmaceutical form:tablets Route of administration: oral administration

Interventions

Sarilumab SAR153191 (REGN88)

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Intervention Type: DRUG

Sarilumab-matching placebo

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Prednisone-matching placebo

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

Intervention Type: DRUG

Prednisone

Pharmaceutical form:tablets Route of administration: oral administration

Intervention Type: DRUG

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400003

Upland, California, United States

Investigational Site Number 8400005

Denver, Colorado, United States

Investigational Site Number 8400009

Stamford, Connecticut, United States

Investigational Site Number 8400002

Boca Raton, Florida, United States

Investigational Site Number 8400014

Iowa City, Iowa, United States

Investigational Site Number 8400006

Boston, Massachusetts, United States

Investigational Site Number 8400022

New York, New York, United States

Investigational Site Number 8400011

Dallas, Texas, United States

Investigational Site Number 8400025

Lufkin, Texas, United States

Investigational Site Number 8400015

Spokane, Washington, United States

Investigational Site Number 0320001

Buenos Aires, , Argentina

Investigational Site Number 0320005

Buenos Aires, , Argentina

Investigational Site Number 0320002

Caba, , Argentina

Investigational Site Number 0320003

San Miguel de Tucumán, , Argentina

Investigational Site Number 0360003

Camberwell, , Australia

Investigational Site Number 0360001

Kogarah, , Australia

Investigational Site Number 0360002

Maroochydore, , Australia

Investigational Site Number 0360004

Woodville South, , Australia

Investigational Site Number 0560003

Ghent, , Belgium

Investigational Site Number 0560001

Leuven, , Belgium

Investigational Site Number 1240007

Hamilton, , Canada

Investigational Site Number 1240010

Montreal, , Canada

Investigational Site Number 1240001

Rimouski, , Canada

Investigational Site Number 1240005

Sherbrooke, , Canada

Investigational Site Number 1240003

Trois-Rivières, , Canada

Investigational Site Number 2330001

Tallinn, , Estonia

Investigational Site Number 2500005

Brest, , France

Investigational Site Number 2500011

Caen, , France

Investigational Site Number 2500015

Le Kremlin-Bicêtre, , France

Investigational Site Number 2500010

Lille, , France

Investigational Site Number 2500002

Montivilliers, , France

Investigational Site Number 2500003

Montpellier, , France

Investigational Site Number 2500004

Paris, , France

Investigational Site Number 2500016

Pierre-Bénite, , France

Investigational Site Number 2500014

Toulouse, , France

Investigational Site Number 2760008

Bad Abbach, , Germany

Investigational Site Number 2760009

Berlin, , Germany

Investigational Site Number 2760001

Berlin, , Germany

Investigational Site Number 2760002

Dresden, , Germany

Investigational Site Number 2760003

Kirchheim unter Teck, , Germany

Investigational Site Number 2760004

München, , Germany

Investigational Site Number 2760007

Tübingen, , Germany

Investigational Site Number 3480001

Debrecen, , Hungary

Investigational Site Number 3760001

Haifa, , Israel

Investigational Site Number 3760004

Haifa, , Israel

Investigational Site Number 3760003

Kfar Saba, , Israel

Investigational Site Number 3760002

Petah Tikva, , Israel

Investigational Site Number 3760005

Tel Litwinsky, , Israel

Investigational Site Number 3800003

Milan, , Italy

Investigational Site Number 3800001

Milan, , Italy

Investigational Site Number 3800004

Pisa, , Italy

Investigational Site Number 3800002

Reggio Emilia, , Italy

Investigational Site Number 3800005

Rozzano, , Italy

Investigational Site Number 3800008

Verona, , Italy

Investigational Site Number 3920002

Fuchu-Shi, , Japan

Investigational Site Number 3920003

Kamakura-Shi, , Japan

Investigational Site Number 3920005

Kawachinagano-Shi, , Japan

Investigational Site Number 3920001

Takasaki-Shi, , Japan

Investigational Site Number 5280003

Alkmaar, , Netherlands

Investigational Site Number 5280002

Almelo, , Netherlands

Investigational Site Number 5280005

Leeuwarden, , Netherlands

Investigational Site Number 5280004

Nijmegen, , Netherlands

Investigational Site Number 5280008

Rotterdam, , Netherlands

Investigational Site Number 5280007

The Hague, , Netherlands

Investigational Site Number 6430002

Moscow, , Russia

Investigational Site Number 6430001

Moscow, , Russia

Investigational Site Number 6430003

Moscow, , Russia

Investigational Site Number 6430004

Moscow, , Russia

Investigational Site Number 6430008

Saint Petersburg, , Russia

Investigational Site Number 7240004

A Coruña / Santiago de Compostela, , Spain

Investigational Site Number 7240005

Badalona, , Spain

Investigational Site Number 7240001

Getafe, , Spain

Investigational Site Number 7240008

Granada, , Spain

Investigational Site Number 7240002

Madrid, , Spain

Investigational Site Number 7240006

Santander, , Spain

Investigational Site Number 7240007

Valencia, , Spain

Investigational Site Number 7560001

Bern, , Switzerland

Investigational Site Number 7560002

Sankt Gallen, , Switzerland

Investigational Site Number 8260004

Gateshead, , United Kingdom

Investigational Site Number 8260003

Leeds, , United Kingdom

Investigational Site Number 8260009

Manchester, , United Kingdom

Investigational Site Number 8260007

Newport, , United Kingdom

Investigational Site Number 8260002

Plymouth, , United Kingdom

Investigational Site Number 8260001

Southend, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Canada; Estonia; France; Germany; Hungary; Israel; Italy; Japan; Netherlands; Russia; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40544861 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37792612 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002989-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1201-0777

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15160

Identifier Type: -

Identifier Source: org_study_id