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

Polymyalgia Rheumatica Clinical Trial

— REPLENISH  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05767034
• Other study ID #: CAIN457C22301
• Secondary ID: 2022-501895-25-0
• Status: Recruiting
• Phase: Phase 3
• Start date: March 22, 2023
• Est. completion date: February 17, 2026

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: February 17, 2026
• Est. primary completion date: September 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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) 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) 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 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

• 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

Related Conditions & MeSH terms

• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

Drug:
• Secukinumab 300 mg
Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen
• Secukinumab 150 mg
Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen

Other:
• Placebo to secukinumab
Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
Australia	Novartis Investigative Site	Heidelberg Heights	Victoria
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Parramatta
Australia	Novartis Investigative Site	Southport	Queensland
Australia	Novartis Investigative Site	Victoria Park	Western Australia
Australia	Novartis Investigative Site	Westmead	New South Wales
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Sao Paulo
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Quebec
Chile	Novartis Investigative Site	Santiago	RM
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Vina del Mar	Region De Valparaiso
Chile	Novartis Investigative Site	Vitacura	Santiago
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Hlucin	Czech Republic
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
Czechia	Novartis Investigative Site	Uherske Hradiste
Czechia	Novartis Investigative Site	Zlin
Denmark	Novartis Investigative Site	Aarhus
Denmark	Novartis Investigative Site	Esbjerg
Denmark	Novartis Investigative Site	Gandrup
Denmark	Novartis Investigative Site	Vejle
France	Novartis Investigative Site	Aix en Provence
France	Novartis Investigative Site	Angers Cedex 9
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Cholet
France	Novartis Investigative Site	Colmar Cedex
France	Novartis Investigative Site	Corbeil Essonnes
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Limoges	Haute Vienne
France	Novartis Investigative Site	Montpellier Cedex 5
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris 13
France	Novartis Investigative Site	Reims Cedex
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Toulon Cedex 9	Val De Marne
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Bad Doberan
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Ratingen
Germany	Novartis Investigative Site	Rendsburg
Germany	Novartis Investigative Site	Wuerzburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Nyiregyhaza
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Veszprem
Israel	Novartis Investigative Site	Holon
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Bolzano	BZ
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Perugia	PG
Italy	Novartis Investigative Site	Reggio Emilia	RE
Japan	Novartis Investigative Site	Asahikawa-city	Hokkaido
Japan	Novartis Investigative Site	Beppu	Oita
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Chuo-city	Yamanashi
Japan	Novartis Investigative Site	Fuchu	Tokyo
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Ichikawa	Chiba
Japan	Novartis Investigative Site	Kawachinagano	Osaka
Japan	Novartis Investigative Site	Kita-gun	Kagawa
Japan	Novartis Investigative Site	Nagano-city	Nagano
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Ome	Tokyo
Japan	Novartis Investigative Site	Omura	Nagasaki
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka-City	Osaka
Japan	Novartis Investigative Site	Sagamihara-city	Kanagawa
Japan	Novartis Investigative Site	Shimonoseki	Yamaguchi
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Saida
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Mazatlan	Sinaloa
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Poland	Novartis Investigative Site	Bytom
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Panorama
South Africa	Novartis Investigative Site	Stellenbosch
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Santiago De Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Fribourg
Switzerland	Novartis Investigative Site	St Gallen
Turkey	Novartis Investigative Site	Ankara	Cankaya
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Pendik	Istanbul
United Kingdom	Novartis Investigative Site	Barnet
United Kingdom	Novartis Investigative Site	Birkenhead	Wirral
United Kingdom	Novartis Investigative Site	Hull
United States	Stryde Research-Allen Arthritis	Allen	Texas
United States	Piedmont Hospital .	Atlanta	Georgia
United States	Rheuma Asso of South Florida	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Providence Medical Center	Burbank	California
United States	Low Country Rheumatology PA Articulitis Healthcare	Charleston	South Carolina
United States	Good Samaritan Regional Medical Ctr Rheumatology	Corvallis	Oregon
United States	Klein and Associates	Cumberland	Maryland
United States	Klein and Associates Rheumatology	Cumberland	Maryland
United States	Arthritis Center of North Georgia	Gainesville	Georgia
United States	UF Health Cancer Center Rheumatology	Gainesville	Florida
United States	DM Clinical Research Rheumatology	Houston	Texas
United States	Prolato Clinical Research Center .	Houston	Texas
United States	Novartis Investigative Site	Iowa City	Iowa
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Kansas City Physician Partners	Kansas City	Missouri
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Southwest Rheum Rsrch LLC	Mesquite	Texas
United States	Paramount Med Rsrch and Consult LLC	Middleburg Heights	Ohio
United States	Hospital for Special Surgery	New York	New York
United States	Arizona Arthritis and Rheumatology Associates PLLC .	Paradise Valley	Arizona
United States	Sun Valley Arthritis Center Ltd	Peoria	Arizona
United States	AZ Arthritis and Rheumtlgy Rsh PLLC	Phoenix	Arizona
United States	Shores Rheumatology	Saint Clair Shores	Michigan
United States	Accurate Clinical Research, Inc. .	San Antonio	Texas
United States	Precn Comprehensive Clnl Rsch Solns	San Leandro	California
United States	Inspire Santa Fe Medical Group Rheumatology	Santa Fe	New Mexico
United States	Providence Saint Johns Health Ctr Main	Santa Monica	California
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Millennium Clinical Trials	Simi Valley	California
United States	Arthritis Northwest PLLC .	Spokane	Washington
United States	Advanced Rheumatology of Houston .	Spring	Texas
United States	West Broward Rheumatology Assoc Inc	Tamarac	Florida
United States	Center for Rheumatology Research Rheumatology	West Hills	California
United States	Florida Medical Clinic PA .	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Lebanon,  Mexico,  Netherlands,  Poland,  South Africa,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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