Clinical trial NCT05767034: Phase III Study of Efficacy and Safety of Secukinumab Versus Placebo, in Combination With Glucocorticoid Taper Regimen, in Patients With Polymyalgia Rheumatica (PMR)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Polymyalgia Rheumatica
Keywords: Polymyalgia Rheumatica
secukinumab
monoclonal antibody
prednisone taper regimen
glucocorticoid
PMR
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-03-14
Enrollment: 381
Sex: ALL
Minimum age (years): 50
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants achieving sustained remission
timeFrame: at Week 52
Secondary outcomes:
measure: Proportion of patients achieving complete sustained remission
timeFrame: 52 Weeks
measure: Adjusted annual cumulative glucocorticoid (GC) dose adjusted by duration of study follow-up
timeFrame: 52 Weeks
measure: Time to first use of escape treatment or rescue treatment as measured in days
timeFrame: 52 Weeks
measure: Change in FACIT-Fatigue Score
timeFrame: 52 Weeks
measure: Change in HAQ-DI score
timeFrame: 52 Weeks
Other outcomes:
Locations:
city: Avondale
country: United States
facility: Arizona Arthritis and Rheumatology Associates PLLC
state: Arizona
city: Peoria
country: United States
facility: Sun Valley Arthritis Center Ltd
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheumtlgy Rsh PLLC
state: Arizona
city: San Leandro
country: United States
facility: Precn Comprehensive Clnl Rsch Solns
state: California
city: Santa Monica
country: United States
facility: Providence Saint Johns Health Ctr
state: California
city: West Hills
country: United States
facility: Center for Rheumatology Research
state: California
city: Westlake Village
country: United States
facility: Millennium Clinical Trials
state: California
city: Boca Raton
country: United States
facility: Rheumatology Associates of South Florida
state: Florida
city: Gainesville
country: United States
facility: UF Health Cancer Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Res Ctr
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates Inc
state: Florida
city: Gainesville
country: United States
facility: Southeastern Rheumatology Alliance
state: Georgia
city: Hagerstown
country: United States
facility: Klein and Associates
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Clair Shores
country: United States
facility: Clinical Research Inst of MI
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Physician Partners
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Middleburg Heights
country: United States
facility: Paramount Med Rsrch and Consult LLC
state: Ohio
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Accurate Clinical Research Inc
state: Texas
city: Spring
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Southport
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Heidelberg Heights
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parramatta
country: Australia
facility: Novartis Investigative Site
city: Brugge
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Cali
country: Colombia
facility: Novartis Investigative Site
state: Valle Del Cauca
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Hlucin
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Zlin
country: Czechia
facility: Novartis Investigative Site
city: Aarhus N
country: Denmark
facility: Novartis Investigative Site
city: Esbjerg
country: Denmark
facility: Novartis Investigative Site
city: Gandrup
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Limoges
country: France
facility: Novartis Investigative Site
state: Haute Vienne
city: Toulon Cedex 9
country: France
facility: Novartis Investigative Site
state: Val De Marne
city: Aix en Provence
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Cholet
country: France
facility: Novartis Investigative Site
city: Colmar Cedex
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Montpellier 5
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Ratingen
country: Germany
facility: Novartis Investigative Site
city: Rendsburg
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Veszprem
country: Hungary
facility: Novartis Investigative Site
city: Reykjavik
country: Iceland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Bolzano
country: Italy
facility: Novartis Investigative Site
state: BZ
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: RE
city: Ichikawa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Asahikawa-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kita-gun
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Sagamihara-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Nagano-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Beppu
country: Japan
facility: Novartis Investigative Site
state: Oita
city: Kawachinagano
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka-City
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fuchu
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Ome
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shimonoseki
country: Japan
facility: Novartis Investigative Site
state: Yamaguchi
city: Chuo
country: Japan
facility: Novartis Investigative Site
state: Yamanashi
city: Okayama
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Almelo
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Bytom
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
city: Stellenbosch
country: South Africa
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Bilbao
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
state: SE
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Fribourg
country: Switzerland
facility: Novartis Investigative Site
city: St Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Barnet
country: United Kingdom
facility: Novartis Investigative Site
city: Hull
country: United Kingdom
facility: Novartis Investigative Site
city: Wolverhampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: