Clinical trial NCT01350804: Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Anti-Tumor Necrosis Factor α (Anti-TNFα) Agents (CAIN457F2309 and CAIN457F2309E1)
Official title: A Randomized, Double-blind, Placebo- and Active-controlled Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Safety, Tolerability and Long Term Efficacy up to 1 Year in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents (CAIN457F2309) and A Four Year Extension Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Rheumatoid Arthritis (CAIN457F2309E1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
RA
ACR
inflammatory joints
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-05-10
Enrollment: 551
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The core and extension studies assessed the safety and efficacy of secukinumab when added to a background therapy in patients with active rheumatoid arthritis who are intolerant to or have had an inadequate response to anti-TNF-α agents. Patients received either secukinumab, placebo or abatacept (active comparator). The core study was completed. However, the extension study was prematurely terminated after the primary endpoint analysis of the core study at week 24 had demonstrated numerically higher efficacy for the active comparator abatacept compared to secukinumab.


Eligibility criteria: Inclusion Criteria:

* Male or non-pregnant, non-lactating female patients
* Presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening
* At Baseline: Disease activity criteria defined by \>= 6 tender joints out of 68 and \>= 6 swollen joints out of 66

WITH at least 1 of the following at screening:

* Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies positive OR
* Rheumatoid Factor positive

AND WITH at least 1 of the following at screening:

* High sensitivity C-Reactive Protein (hsCRP) \>= 10 mg/L OR
* Erythrocyte Sedimentation Rate (ESR) \>= 28 millimeter (mm)/1st hour
* Patients must have been taking at least one anti-TNF-α agent given at an approved dose for at least 3 months before randomization and have experienced an inadequate response to treatment or have been intolerant to at least one administration of an anti-TNF-α agent
* Patients must be taking MTX or any other DMARD (but not more than 1 DMARD) for at least 3 months before randomization and have to be on a stable dose at least 4 weeks before randomization (7.5 to 25 mg/week for MTX or other DMARD at maximum tolerated dose)

Exclusion Criteria:

* Chest x-ray with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician
* RA patients functional status class IV according to the ACR 1991 revised criteria
* Patients who have ever received biologic immunomodulating agents except for those targeting TNFα
* Previous treatment with any cell-depleting therapies

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).
timeFrame: week 24
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)
timeFrame: baseline, week 24
measure: Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: baseline, week 24
measure: Percentage of Participants Achieving ACR50
timeFrame: week 24
measure: Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24
measure: Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM)
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in HAQ-DI - Observed Data
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: Change From Baseline in hsCRP - Observed Data
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data
timeFrame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Vestavia
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Freemont
country: United States
facility: Novartis Investigative Site
state: California
city: Pomona
country: United States
facility: Novartis Investigative Site
state: California
city: Upland
country: United States
facility: Novartis Investigative Site
state: California
city: Van Nuys
country: United States
facility: Novartis Investigative Site
state: California
city: Bridgeport
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Aventura
country: United States
facility: Novartis Investigative Site
state: Florida
city: Boca Raton
country: United States
facility: Novartis Investigative Site
state: Florida
city: Hialeah
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Palm Harbor
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pembroke Pines
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: Plantation
country: United States
facility: Novartis Investigative Site
state: Florida
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Coeur d'Alene
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Morton Grove
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Springfield
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Wichita
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Bowling Green
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Lexington
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Lansing
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Eagan
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Richmond Heights
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Zanesville
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Jackson
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Kingsport
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Carrollton
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Sugar Land
country: United States
facility: Novartis Investigative Site
state: Texas
city: Waco
country: United States
facility: Novartis Investigative Site
state: Texas
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: Clarksburg
country: United States
facility: Novartis Investigative Site
state: West Virginia
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
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
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Russe
country: Bulgaria
facility: Novartis Investigative Site
city: Sevlievo
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: St. John's
country: Canada
facility: Novartis Investigative Site
state: Newfoundland and Labrador
city: Sainte-Foy
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
city: Bruntal
country: Czech Republic
facility: Novartis Investigative Site
city: Ostrava
country: Czech Republic
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czech Republic
facility: Novartis Investigative Site
city: Zlin
country: Czech Republic
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Cahors
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Cottbus
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Gommern
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Osnabrück
country: Germany
facility: Novartis Investigative Site
city: Zerbst
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Valeggio Sul Mincio
country: Italy
facility: Novartis Investigative Site
state: (vr)
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Mexicali
country: Mexico
facility: Novartis Investigative Site
state: Baja California
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Culiacan
country: Mexico
facility: Novartis Investigative Site
state: Sinaloa
city: Iasi
country: Romania
facility: Novartis Investigative Site
city: Korolev
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Petrozavodsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Tula
country: Russian Federation
facility: Novartis Investigative Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Piestany
country: Slovakia
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Huang Y, Fan Y, Liu Y, Xie W, Zhang Z. Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis of phase III randomized controlled trials. Clin Rheumatol. 2019 Oct;38(10):2765-2776. doi: 10.1007/s10067-019-04595-1. Epub 2019 May 14.
citation: Blanco FJ, Moricke R, Dokoupilova E, Codding C, Neal J, Andersson M, Rohrer S, Richards H. Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active Comparator- and Placebo-Controlled Study. Arthritis Rheumatol. 2017 Jun;69(6):1144-1153. doi: 10.1002/art.40070. Epub 2017 May 3.