Phase III Study of Efficacy and Safety of Secukinumab Versus Placebo, in Combination With Glucocorticoid Taper Regimen, in Patients With Polymyalgia Rheumatica (PMR) (REPLENISH)

A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase III Trial to Evaluate Efficacy and Safety of Secukinumab Administered Subcutaneously Versus Placebo, in Combination With a Glucocorticoid Taper Regimen, in Patients With Polymyalgia Rheumatica (PMR)

The purpose of this study is to demonstrate the efficacy and safety of secukinumab 300 milligram (mg) and 150 mg administered subcutaneously (s.c.) for 52 weeks in combination with prednisone tapered over 24 weeks in adult participants with PMR who have recently relapsed.

Study Overview

• Status: Completed
• Conditions: Polymyalgia Rheumatica
• Intervention / Treatment: Drug: Secukinumab 300 mg; Drug: Secukinumab 150 mg; Other: Placebo to secukinumab

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study with two secukinumab dose regimens in approximately 360 PMR patients who had recently relapsed. The study consists of: screening (up to 6 weeks); treatment period (52 weeks, with last IMP administration at 48 weeks, active drug or placebo) in combination with prednisone tapered over 24 weeks; treatment-free follow-up (up to 24 weeks). Adult males and females of at least 50 years of age with a recent PMR relapse (within 12 weeks from Baseline) will be included. Dosing will be once every week for the first 4 weeks, and once every 4 weeks thereafter via pre-filled syringe.

The primary objective is to demonstrate the efficacy of secukinumab 300 mg subcutaneously in combination with a 24-week glucocorticoid (GC) taper regimen compared with placebo with respect to the proportion of patients in sustained remission at Week 52. Primary secondary objectives are to assess difference in proportion of patients achieving complete sustained remission at Week 52, adjusted annual cumulative GC dose and time to first use of escape treatment or rescue treatment through Week 52. Key safety data will be collected, along with Patient Reported Outcomes.

• Study Type: Interventional
• Enrollment (Actual): 381
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1055AAF
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1119ACN
      • Novartis Investigative Site
    • Quilmes, Buenos Aires, Argentina, B1878GEG
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Parramatta, New South Wales, Australia, 2150
      • Novartis Investigative Site
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Novartis Investigative Site
  • Victoria
    • Heidelberg Heights, Victoria, Australia, 3081
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liège, Belgium, 4000
    • Novartis Investigative Site
• Brazil
  • São Paulo, Brazil, 01409-902
    • Novartis Investigative Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90480-000
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04038-002
      • Novartis Investigative Site
• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 3M7
      • Novartis Investigative Site
• Chile
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2531172
      • Novartis Investigative Site
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7500571
      • Novartis Investigative Site
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Novartis Investigative Site
    • Santiago, Santiago Metropolitan, Chile, 8380465
      • Novartis Investigative Site
• Colombia
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080002
      • Novartis Investigative Site
    • Barranquilla, Atlántico, Colombia, 080020
      • Novartis Investigative Site
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110221
      • Novartis Investigative Site
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760042
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 638 00
    • Novartis Investigative Site
  • Hlučín, Czechia, 748 01
    • Novartis Investigative Site
  • Prague, Czechia, 128 00
    • Novartis Investigative Site
  • Prague, Czechia, 140 00
    • Novartis Investigative Site
  • Uherské Hradiště, Czechia, 686 01
    • Novartis Investigative Site
  • Zlín, Czechia, 760 01
    • Novartis Investigative Site
  • Czech Republic
    • Prague, Czech Republic, Czechia, 140 00
      • Novartis Investigative Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Novartis Investigative Site
  • Esbjerg, Denmark, 6700
    • Novartis Investigative Site
  • Gandrup, Denmark, 9362
    • Novartis Investigative Site
  • Vejle, Denmark, DK-7100
    • Novartis Investigative Site
• France
  • Aix-en-Provence, France, 13616
    • Novartis Investigative Site
  • Brest, France, 29200
    • Novartis Investigative Site
  • Cholet, France, 49325
    • Novartis Investigative Site
  • Colmar, France, 68024
    • Novartis Investigative Site
  • Dijon, France, 21000
    • Novartis Investigative Site
  • Le Mans, France, 72000
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Reims, France, 51092
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Haute Vienne
    • Limoges, Haute Vienne, France, 87000
      • Novartis Investigative Site
  • Val De Marne
    • Toulon, Val De Marne, France, 83800
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Erlangen, Germany, 91056
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Ratingen, Germany, 40878
    • Novartis Investigative Site
  • Rendsburg, Germany, 24768
    • Novartis Investigative Site
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Novartis Investigative Site
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1027
    • Novartis Investigative Site
  • Szeged, Hungary, 6725
    • Novartis Investigative Site
  • Veszprém, Hungary, 8200
    • Novartis Investigative Site
• Iceland
  • Reykjavik, Iceland, 101
    • Novartis Investigative Site
• Ireland
  • Dublin, Ireland, D03 VX82
    • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • BZ
    • Bolzano, BZ, Italy, 39100
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20132
      • Novartis Investigative Site
    • Milan, MI, Italy, 20100
      • Novartis Investigative Site
    • Milan, MI, Italy, 20157
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06129
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
• Japan
  • Okayama, Japan, 700-8607
    • Novartis Investigative Site
  • Osaka, Japan, 5340021
    • Novartis Investigative Site
  • Chiba
    • Ichikawa, Chiba, Japan, 2728516
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 8140180
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 0708644
      • Novartis Investigative Site
  • Kagawa-ken
    • Kita-gun, Kagawa-ken, Japan, 7610793
      • Novartis Investigative Site
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0392
      • Novartis Investigative Site
    • Yokohama, Kanagawa, Japan, 222-0036
      • Novartis Investigative Site
  • Nagano
    • Nagano, Nagano, Japan, 3808582
      • Novartis Investigative Site
  • Oita Prefecture
    • Beppu, Oita Prefecture, Japan, 8740011
      • Novartis Investigative Site
  • Osaka
    • Kawachi-Nagano, Osaka, Japan, 5868521
      • Novartis Investigative Site
    • Osaka, Osaka, Japan, 550-0006
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo Ku, Tokyo, Japan, 1138431
      • Novartis Investigative Site
    • Fuchū, Tokyo, Japan, 1838524
      • Novartis Investigative Site
    • Ōme, Tokyo, Japan, 198-0042
      • Novartis Investigative Site
  • Yamaguchi
    • Shimonoseki, Yamaguchi, Japan, 750-0041
      • Novartis Investigative Site
  • Yamanashi
    • Chūō, Yamanashi, Japan, 409-3898
      • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 166830
    • Novartis Investigative Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
  • Overijssel
    • Almelo, Overijssel, Netherlands, 7609 PP
      • Novartis Investigative Site
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3079 DZ
      • Novartis Investigative Site
• Poland
  • Bytom, Poland, 41 902
    • Novartis Investigative Site
  • Lublin, Poland, 20-607
    • Novartis Investigative Site
  • Warsaw, Poland, 02-665
    • Novartis Investigative Site
  • Warsaw, Poland, 02-118
    • Novartis Investigative Site
  • Warsaw, Poland, 02-637
    • Novartis Investigative Site
• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
      • Novartis Investigative Site
    • Cape Town, Western Cape, South Africa, 7405
      • Novartis Investigative Site
    • Stellenbosch, Western Cape, South Africa, 7600
      • Novartis Investigative Site
• Spain
  • A Coruña, Spain, 15006
    • Novartis Investigative Site
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Seville, Spain, 41013
    • Novartis Investigative Site
  • Valencia, Spain, 46010
    • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Bizkaia
    • Bilbao, Bizkaia, Spain, 48013
      • Novartis Investigative Site
• Sweden
  • SE
    • Stockholm, SE, Sweden, 113 65
      • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Fribourg, Switzerland, 1708
    • Novartis Investigative Site
  • Sankt Gallen, Switzerland, 9007
    • Novartis Investigative Site
• United Kingdom
  • Barnet, United Kingdom, EN5 3DJ
    • Novartis Investigative Site
  • Hull, United Kingdom, HU3 2RW
    • Novartis Investigative Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Novartis Investigative Site
• United States
  • Arizona
    • Avondale, Arizona, United States, 85392
      • Arizona Arthritis and Rheumatology Associates PLLC
    • Peoria, Arizona, United States, 85381
      • Sun Valley Arthritis Center Ltd
    • Phoenix, Arizona, United States, 85032
      • AZ Arthritis and Rheumtlgy Rsh PLLC
  • California
    • San Leandro, California, United States, 94578
      • Precn Comprehensive Clnl Rsch Solns
    • Santa Monica, California, United States, 90404
      • Providence Saint Johns Health Ctr
    • West Hills, California, United States, 91307
      • Center for Rheumatology Research
    • Westlake Village, California, United States, 91361
      • Millennium Clinical Trials
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Rheumatology Associates of South Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Cancer Center
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Res Ctr
    • Tamarac, Florida, United States, 33321
      • West Broward Rheumatology Associates Inc
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Southeastern Rheumatology Alliance
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Klein and Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48081
      • Clinical Research Inst of MI
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City Physician Partners
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Med Rsrch and Consult LLC
  • Texas
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center
    • Houston, Texas, United States, 77070
      • DM Clinical Research
    • San Antonio, Texas, United States, 78229
      • Accurate Clinical Research Inc
    • Spring, Texas, United States, 77382
      • Advanced Rheumatology of Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study
• Male or non-pregnant, non-lactating female participants at least 50 years of age.

• Diagnosis of PMR according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria: Participants ≥ 50 years of age with a history of bilateral shoulder pain accompanied by elevated C-reactive protein (CRP) concentration (≥ 10 mg/L) and/or elevated erythrocyte sedimentation rate (ESR) (≥ 30 mm/hr) who scored at least 4 points from the following optional classification criteria:

  • Morning stiffness > 45 minutes (min) (2 points)
  • Hip pain or restricted range of motion (1 point)
  • Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2 points)
  • Absence of other joint involvement (1 point)
• Participants must have a history of being treated for at least 8 consecutive weeks with prednisone ≥ 10 mg/day, or equivalent dose of another GC at any time prior to screening

• Participants must have had at least one episode of PMR relapse while attempting to taper prednisone at a dose that is ≥ 5 mg/day (or equivalent dose of another GC) within the past 12 weeks prior to BSL. Diagnosis of a PMR relapse is defined as participant meeting both of the following:

  • Recurrence of bilateral shoulder girdle and/or bilateral hip girdle pain associated with inflammatory stiffness with or without additional symptoms indicative of PMR relapse (such as constitutional symptoms) within 12 weeks prior to BSL that are in the opinion of the Investigator not due to other diseases that may mimic PMR such as osteoarthritis in shoulders or hips, polyarticular calcium pyrophosphate deposition disease, rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia.
  • Elevated ESR (≥ 30 mm/hr) and/or elevated CRP (> upper limit of normal (ULN)) attributable to PMR at the time of relapse and/or at screening
• Participants must have been treated as per local treatment recommendations following the latest PMR relapse and must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 25 mg/day at screening and during the screening period

Exclusion Criteria:

• Evidence/history of GCA as indicated by typical (cranial) symptoms (e.g., persistent or recurrent localized headache, temporal artery or scalp tenderness, jaw claudication, blurry or loss of vision, symptoms of stroke), extremity claudication, imaging and/or temporal artery biopsy result
• 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 or history of neuropathic muscular diseases or fibromyalgia
• Inadequately treated hypothyroidism (e.g., persistence of symptoms, lack of normalization of serum TSH despite regular hormonal replacement treatment)
• Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
• Participants treated with tocilizumab or other IL-6/IL6-receptor inhibitors within 12 weeks or within 5 half-lives (whichever is longer) prior to BSL; participant who did not respond to or experienced a relapse during treatment are excluded from enrollment into the study Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab 300 mg; randomized in 1:1:1 ratio every 4 weeks	Drug: Secukinumab 300 mg; Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen; Other Names: AIN457
Experimental: Secukinumab 150 mg; randomized in 1:1:1 ratio every 4 weeks	Drug: Secukinumab 150 mg; Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen; Other Names: AIN457
Placebo Comparator: Placebo to secukinumab; randomized in 1:1:1 ratio every 4 weeks	Other: Placebo to secukinumab; Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving sustained remission	Sustained remission at Week 52 is defined as a participant meeting all of the following: ● achieved remission at Week 12 AND all of the following, sustained from Week 12 to Week 52: no recurrence of signs or symptoms, attributable to PMR, that requires escape treatment or rescue treatment; no new diagnosis of Giant cell arteritis (GCA), that requires escape treatment or rescue treatment Remission at Week 12 is defined as a participant meeting all of the following at Week 12: no use of escape treatment or rescue treatment prior to Week 12; no signs or symptoms attributable to PMR, that requires escape treatment or use of rescue treatment, at Week 12; no new diagnosis of GCA, that requires escape treatment or rescue treatment, at Week 12	at Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving complete sustained remission	Complete sustained remission at Week 52 is defined as participant meeting all of the following: achieved sustained remission; no clinically relevant elevation of Erythrocyte sedimentation Rate (ESR) and/or C-reactive protein (CRP) at ≥2 consecutive scheduled visits from Week 12 to Week 52	52 Weeks
Adjusted annual cumulative glucocorticoid (GC) dose adjusted by duration of study follow-up	Adjusted annual cumulative GC dose is cumulative GC dose through Week 52 adjusted by duration of study follow-up	52 Weeks
Time to first use of escape treatment or rescue treatment as measured in days	First use of escape treatment or rescue treatment is defined as the first time when the escape treatment or rescue treatment is used	52 Weeks
Change in FACIT-Fatigue Score	The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. The purpose of collecting available FACIT-Fatigue data is to assess the impact of fatigue on participants with PMR.	52 Weeks
Change in HAQ-DI score	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is used to assess the long-term influence of chronic disease on a participant's level of functional ability and activity restriction. The purpose of the HAQ-DI is to assess the functional ability of subjects with PMR.	52 Weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Sun MM, Pope JE. Polymyalgia rheumatica and giant cell arteritis: diagnosis and management. Curr Opin Rheumatol. 2025 Jan 1;37(1):32-38. doi: 10.1097/BOR.0000000000001059. Epub 2024 Oct 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2023
• Primary Completion (Actual): September 10, 2025
• Study Completion (Actual): February 16, 2026

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: monoclonal antibody; glucocorticoid; PMR; secukinumab; Polymyalgia Rheumatica; prednisone taper regimen
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Polymyalgia Rheumatica; Immunologic Factors; Physiological Effects of Drugs; secukinumab
• Other Study ID Numbers: CAIN457C22301; 2022-501895-25-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No