Clinical trial NCT01377012: Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy up to 2 Years of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Anti-TNFα Agents
Official title: A Randomized, Double-blind, Placebo-controlled Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Safety, Tolerability and Long Term Efficacy up to 2 Years in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents (CAIN457F2302) and a Three Year Extension Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Rheumatoid Arthritis (CAIN457F2302E1)
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: 2011-06-20
Enrollment: 637
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. The core study was completed. However, the extension study was terminated early (unrelated to safety) due to the results of study AIN457F2309, which indicated the efficacy of AIN457 was not comparable to the currently available RA treatment, abatacept, thus leading to closing of the AIN457 RA program.

Detailed description: CAIN457F2302 (Core Study): Completed Sep 9 2015

CAIN457F2302E1 (Extension study): terminated early May 26 2015, ((unrelated to safety) due to the results of study AIN457F2309, which indicated the efficacy of AIN457 was not comparable to the currently available RA treatment, abatacept, thus leading to closing of the AIN457 RA program.

Eligibility criteria: Inclusion criteria:

* Male or non-pregnant, non-lactating female patients
* Presence of RA classified by American College of Rheumatology (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 (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 mm/1st hr
* 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 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 Japan only: 6 to 25 mg/week)

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 including but not limited to anti-CD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)
* Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Core Study: Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20) at Week 24
timeFrame: Week 24
measure: Extension Phase: Percentage of Patients Achieving a American College of Rheumatology Response ACR20, ACR50 and ACR70
timeFrame: up to week 260
Secondary outcomes:
measure: Core Study: Change From Baseline and Week 24 in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: Baseline, Week 24
measure: Core Study: Change From Baseline at Week 24 in Van Der Heijde Total Modified Sharp Score
timeFrame: Week 24
measure: Core Study Percentage of Patients Achieving Major Clinical Response (Continuous Six-month Period of ACR70 Response During the 1 Year Period) at Week 52
timeFrame: 52 week
measure: Extension Phase: Change in Baseline of RA Disease Activity as Measured by Disease Activity Score (DAS28)
timeFrame: week 260
measure: Extension Phase: Proportion of Subjects Achieving Low Disease Activity and Good/Moderate European League Against Rheumatism (EULAR) Responses
timeFrame: up to week 260
measure: Extension Phase: Proportion of Subjects Achieving ACR/(EULAR) Remission
timeFrame: up to week 260
measure: Extension Phase: Changes in Baseline of Quality of Life (Qol) Outcomes Measured by Medical Outcome Short Form SF-36 v2
timeFrame: Baseline, up to week 260
measure: Extension Phase: Immunogenicity Against Secukinumab
timeFrame: up to week 260
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Paradise Valley
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Peoria
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Santa Monica
country: United States
facility: Novartis Investigative Site
state: California
city: Stanford
country: United States
facility: Novartis Investigative Site
state: California
city: Torrance
country: United States
facility: Novartis Investigative Site
state: California
city: Upland
country: United States
facility: Novartis Investigative Site
state: California
city: Hialeah
country: United States
facility: Novartis Investigative Site
state: Florida
city: Largo
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: South Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tamarac
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Canton
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Bowling Green
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Wheaton
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Eagan
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Asheville
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Durham
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Gallipolis
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Columbia
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Greenville
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Jackson
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Johnson City
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Lanus
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: St. Catharines
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Sainte-Foy
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bogotá
country: Colombia
facility: Novartis Investigative Site
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
city: Medellín
country: Colombia
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Eger
country: Hungary
facility: Novartis Investigative Site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Veszprem
country: Hungary
facility: Novartis Investigative Site
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Amravati
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Mumbai
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Ajmer
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Secunderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Pieve di Coriano
country: Italy
facility: Novartis Investigative Site
state: MN
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Chiba-city
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Yotsukaido-city
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Iizuka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Kitakyushu-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Takasaki-city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Hiroshima-city
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kamakura-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kawasaki-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sagamihara-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kumamoto-city
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Taihaku-ku
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Nagano-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Nagasaki-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Sasebo-city
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Kurashiki-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Tsukubo-gun
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Hannan-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kawachinagano-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kawagoe
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Tokorozawa-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Fuji-city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Hamamatsu-city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Fuchu
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Takaoka-city
country: Japan
facility: Novartis Investigative Site
state: Toyama
city: Toyama-city
country: Japan
facility: Novartis Investigative Site
state: Toyama
city: Shimonoseki-city
country: Japan
facility: Novartis Investigative Site
state: Yamaguchi
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Mexicali
country: Mexico
facility: Novartis Investigative Site
state: Baja California
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: Culiacan
country: Mexico
facility: Novartis Investigative Site
state: Sinaloa
city: Panama City
country: Panama
facility: Novartis Investigative Site
state: Panamá
city: Panama City
country: Panama
facility: Novartis Investigative Site
state: Panamá
city: Ponce
country: Puerto Rico
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Leytonstone
country: United Kingdom
facility: Novartis Investigative Site
state: London
city: Cannock
country: United Kingdom
facility: Novartis Investigative Site
state: Staffordshire
city: Salisbury
country: United Kingdom
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: Tahir H, Deodhar A, Genovese M, Takeuchi T, Aelion J, Van den Bosch F, Haemmerle S, Richards HB. Secukinumab in Active Rheumatoid Arthritis after Anti-TNFalpha Therapy: A Randomized, Double-Blind Placebo-Controlled Phase 3 Study. Rheumatol Ther. 2017 Dec;4(2):475-488. doi: 10.1007/s40744-017-0086-y. Epub 2017 Nov 14.