Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents. (REASSURE2)

A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate the Efficacy at 24 Weeks and to Assess the Long Term Efficacy, Safety, Tolerability and Usability up to 5 Years in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents

This study will provide efficacy and safety data of the secukinumab pre-filled syringe (PFS) for subcutaneous self-administration in patients with active rheumatoid arthritis who are intolerant to or have had an inadequate response to anti-TNF-α agents.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Placebo; Biological: Secukinumab (AIN457)

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Mar del Plata, Buenos Aires, Argentina, B7600FZN
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CXH
      • Novartis Investigative Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina
      • Novartis Investigative Site
• Brazil
  • BA
    • Salvador, BA, Brazil, 40050-410
      • Novartis Investigative Site
  • MG
    • Juiz de Fora, MG, Brazil, 36010-570
      • Novartis Investigative Site
  • PR
    • Curitiba, PR, Brazil, 80030-110
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 04266-010
      • Novartis Investigative Site
• Colombia
  • Bogotá, Colombia, 110221
    • Novartis Investigative Site
  • Cali, Colombia
    • Novartis Investigative Site
• Czech Republic
  • Praha 2, Czech Republic, 128 50
    • Novartis Investigative Site
  • Uherske Hradiste, Czech Republic, 686 01
    • Novartis Investigative Site
• Dominican Republic
  • Republica Dominicana
    • Santo Domingo, Republica Dominicana, Dominican Republic
      • Novartis Investigative Site
• Germany
  • Bad Doberan, Germany, 18209
    • Novartis Investigative Site
  • Göttingen, Germany, 37075
    • Novartis Investigative Site
  • Hamburg, Germany, 22081
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Pirna, Germany, 01796
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
    • Heraklion, GR, Greece, 700 13
      • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala, 01010
    • Novartis Investigative Site
• India
  • Andhra Pradesh
    • Secunderabad, Andhra Pradesh, India, 500003
      • Novartis Investigative Site
  • Delhi
    • New Delhi, Delhi, India, 110 060
      • Novartis Investigative Site
  • Maharashtra
    • Pune, Maharashtra, India, 411 040
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411007
      • Novartis Investigative Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302013
      • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24128
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00152
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37100
      • Novartis Investigative Site
• Japan
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 813-0017
      • Novartis Investigative Site
  • Gunma
    • Takasaki-city, Gunma, Japan, 370-0053
      • Novartis Investigative Site
  • Hiroshima
    • Hiroshima-city, Hiroshima, Japan, 733-0032
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 230-0023
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto-city, Kumamoto, Japan, 862-0976
      • Novartis Investigative Site
  • Miyagi
    • Miyagi-gun, Miyagi, Japan, 981-0112
      • Novartis Investigative Site
  • Nagano
    • Nagano-city, Nagano, Japan, 380-8582
      • Novartis Investigative Site
  • Nagasaki
    • Sasebo-city, Nagasaki, Japan, 857-1165
      • Novartis Investigative Site
  • Okayama
    • Setouchi-city, Okayama, Japan, 701-4264
      • Novartis Investigative Site
  • Osaka
    • Kawachinagano-city, Osaka, Japan, 586-8521
      • Novartis Investigative Site
  • Saitama
    • Tokorozawa-city, Saitama, Japan, 359-1111
      • Novartis Investigative Site
  • Shizuoka
    • Hamamatsu-city, Shizuoka, Japan, 430-8558
      • Novartis Investigative Site
  • Toyama
    • Toyama-city, Toyama, Japan, 930-0138
      • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 137-701
      • Novartis Investigative Site
• Panama
  • Panamá
    • Panama City, Panamá, Panama, 0823-01510
      • Novartis Investigative Site
    • Panama City, Panamá, Panama
      • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1050-034
    • Novartis Investigative Site
  • Lisboa, Portugal, 1600-190
    • Novartis Investigative Site
• South Africa
  • Western Cape
    • Panorama, Western Cape, South Africa, 7500
      • Novartis Investigative Site
• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Novartis Investigative Site
  • California
    • Santa Monica, California, United States, 90404
      • Novartis Investigative Site
    • Upland, California, United States, 91786
      • Novartis Investigative Site
  • Florida
    • Miami, Florida, United States, 33135
      • Novartis Investigative Site
    • Pembroke Pines, Florida, United States, 33026
      • Novartis Investigative Site
    • Zephyrhills, Florida, United States, 33542
      • Novartis Investigative Site
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Novartis Investigative Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Novartis Investigative Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Novartis Investigative Site
  • Missouri
    • Lees Summit, Missouri, United States, 64086
      • Novartis Investigative Site
    • St. Louis, Missouri, United States, 63128
      • Novartis Investigative Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Novartis Investigative Site
  • Ohio
    • Zanesville, Ohio, United States, 43701
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Novartis Investigative Site
    • Oklahoma City, Oklahoma, United States, 73134
      • Novartis Investigative Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Novartis Investigative Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Novartis Investigative Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Novartis Investigative Site
    • Nashville, Tennessee, United States, 37203-1424
      • Novartis Investigative Site
  • Texas
    • Amarillo, Texas, United States, 79124
      • Novartis Investigative Site
    • Benbrook, Texas, United States, 76126
      • Novartis Investigative Site
    • Houston, Texas, United States, 77005
      • Novartis Investigative Site
    • Houston, Texas, United States, 77034
      • Novartis Investigative Site
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: • Presence of Rheumatoid Arthritis classified by ACR 2010 revised criteria for at least 3 months •Disease activity defined by ≥6 tender joints out of 68 and ≥ 6 swollen joints out of 66 at baseline and with: Either Anti-CCP antibodies positive OR Rheumatoid Factor positive AND WITH Either hsCRP ≥ 10 mg/L OR ESR ≥28 mm/1st hr •Intake of at least one anti-TNF-α agent such as etanercept, adalimumab, infliximab, certolizumab or golimumab for at least 3 months before entering the study and to have experienced an inadequate response to treatment or to have been intolerant to at least one administration Exclusion Criteria:

• Current RA functional status class IV according to the ACR 1991 revised criteria •Previous use of secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor and/or any history of hypersensitivity to secukinumab or its excipient or to drugs of similar chemical classes. Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab 75 mg; Secukinumab 75 mg s.c.	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); Other Names: AIN457
Experimental: Secukinumab 150 mg; Secukinumab 150 mg s.c.	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); Other Names: AIN457
Placebo Comparator: Placebo; Placebo patients will be re-randomized 1:1 to secukinumab 75 or 150mg s.c. (non-responders at Week 16 will be re-assigned to new treatment at Week 16; responders at Week 16 will be re-assigned to new treatment at Week 24)	Biological: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).	ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20 response results at week 24 used non-responder imputation.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)	The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient's Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.	Week 24
Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)	The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.	Week 24
Percentage of Participants Achieving ACR50	ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR50 response results at week 24 used non-responder imputation.	Week 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: January 15, 2013
• First Posted (Estimate): January 17, 2013

Study Record Updates

• Last Update Posted (Estimate): July 21, 2016
• Last Update Submitted That Met QC Criteria: June 9, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis, RA, IL-17 blocker, subcutaneous, self-injection, AIN457, AIN457F, secukinumab, anti-TNFα, pre-filled syringe
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: CAIN457F2311; 2011-006058-94 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No