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

Rheumatoid Arthritis Clinical Trial

— REASSURE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01377012
• Other study ID #: CAIN457F2302
• Secondary ID: 2011-000275-13
• Status: Completed
• Phase: Phase 3
• First received: June 17, 2011
• Last updated: March 8, 2016
• Start date: August 2011
• Est. completion date: September 2015

Study information

• Verified date: March 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBelgium: Ministry of Social Affairs, Public Health and the EnvironmentCanada: Health CanadaColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosGuatemala: Ministry of Public Health and Social AssistanceHungary: Scientific and Medical Research Council Ethics CommitteeIndia: Ministry of HealthItaly: Ethics CommitteeJapan: Ministry of Health, Labor and WelfareMexico: Federal Commission for Sanitary Risks ProtectionPanama: Ministry of HealthPeru: Ministry of HealthRomania: National Medicines AgencyThailand: Ministry of Public HealthTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of secukinumab when added to a background therapy in patients with active rheumatoid arthritis (RA) who are intolerant to or have had an inadequate response to anti-tumor necrosis factor (TNF)-α agents.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 637
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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-a 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-a 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 TNFa

• 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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Secukinumab (AIN457)
Secukinumab is a human monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind to unique proteins that your body produces. Secukinumab binds and reduces the activity of a cytokine (a "messenger" protein in the body) called Interleukin 17 (IL-17).
• Placebo

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gent
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	St. Catharines	Ontario
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Colombia	Novartis Investigative Site	Bogotá
Colombia	Novartis Investigative Site	Bucaramanga
Colombia	Novartis Investigative Site	Medellín
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Szekesfehervar
Hungary	Novartis Investigative Site	Szolnok
Hungary	Novartis Investigative Site	Veszprem
India	Novartis Investigative Site	Ajmer	Rajasthan
India	Novartis Investigative Site	Amravati	Maharashtra
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Secunderabad	Andhra Pradesh
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Pieve di Coriano	MN
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Verona	VR
Japan	Novartis Investigative Site	Chiba-city	Chiba
Japan	Novartis Investigative Site	Fuchu	Tokyo
Japan	Novartis Investigative Site	Fuji-city	Shizuoka
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Hamamatsu-city	Shizuoka
Japan	Novartis Investigative Site	Hannan-city	Osaka
Japan	Novartis Investigative Site	Hiroshima-city	Hiroshima
Japan	Novartis Investigative Site	Iizuka-city	Fukuoka
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kamakura-city	Kanagawa
Japan	Novartis Investigative Site	Kawachinagano-city	Osaka
Japan	Novartis Investigative Site	Kawagoe	Saitama
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Kumamoto-city	Kumamoto
Japan	Novartis Investigative Site	Kurashiki-city	Okayama
Japan	Novartis Investigative Site	Nagano-city	Nagano
Japan	Novartis Investigative Site	Nagasaki-city	Nagasaki
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sagamihara-city	Kanagawa
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sasebo-city	Nagasaki
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Shimonoseki-city	Yamaguchi
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Taihaku-ku	Miyagi
Japan	Novartis Investigative Site	Takaoka-city	Toyama
Japan	Novartis Investigative Site	Takasaki-city	Gunma
Japan	Novartis Investigative Site	Tokorozawa-city	Saitama
Japan	Novartis Investigative Site	Toyama-city	Toyama
Japan	Novartis Investigative Site	Tsukubo-gun	Okayama
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yotsukaido-city	Chiba
Mexico	Novartis Investigative Site	Culiacan	Sinaloa
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Mexicali	Baja California
Mexico	Novartis Investigative Site	Mexicali	Baja California
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Panama	Novartis Investigative Site	Panama City	Panamá
Panama	Novartis Investigative Site	Panama City	Panamá
Puerto Rico	Novartis Investigative Site	Ponce
Puerto Rico	Novartis Investigative Site	San Juan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen
Thailand	Novartis Investigative Site	Songkla
Turkey	Novartis Investigative Site	Ankara
United Kingdom	Novartis Investigative Site	Cannock	Staffordshire
United Kingdom	Novartis Investigative Site	Leytonstone	London
United Kingdom	Novartis Investigative Site	Salisbury
United Kingdom	Novartis Investigative Site	Sheffield
United States	Novartis Investigative Site	Asheville	North Carolina
United States	Novartis Investigative Site	Bowling Green	Kentucky
United States	Novartis Investigative Site	Canton	Georgia
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Eagan	Minnesota
United States	Novartis Investigative Site	Gallipolis	Ohio
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Hialeah	Florida
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jackson	Tennessee
United States	Novartis Investigative Site	Johnson City	Tennessee
United States	Novartis Investigative Site	Kansas City	Missouri
United States	Novartis Investigative Site	Largo	Florida
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Mesa	Arizona
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Palm Harbor	Florida
United States	Novartis Investigative Site	Paradise Valley	Arizona
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Santa Monica	California
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigative Site	Stanford	California
United States	Novartis Investigative Site	Tamarac	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Torrance	California
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Colombia,  Guatemala,  Hungary,  India,  Italy,  Japan,  Mexico,  Panama,  Puerto Rico,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	efficacy (proportion of patients achieving an ACR20 response) at 75 mg or 150 mg of secukinumab (AIN457) compared to placebo		Week 24	No
Secondary	improvement (change) of the Health Assessment Questionnaire - Disability Index (HAQ-DI) from baseline on secukinumab 75 mg or 150 mg compared to placebo		Week 24	No
Secondary	change of the van der Heijde total modified Sharp score on secukinumab 75 mg and 150 mg pooled or individual dose is superior to placebo		Week 24	No
Secondary	proportion of patients achieving major clinical response (continuous six-month period of ACR70 response) on secukinumab 75 mg or 150 mg compared to placebo (as originally randomized)		1 Year	No