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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01770379
First received: October 16, 2012
Last updated: June 9, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis
Biological: Secukinumab (AIN457)
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20). [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving ACR50 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    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.



Enrollment: 242
Study Start Date: October 2012
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01770379

  Show 77 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01770379     History of Changes
Other Study ID Numbers: CAIN457F2311  2011-006058-94 
Study First Received: October 16, 2012
Results First Received: May 3, 2016
Last Updated: June 9, 2016
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Republic of Korea: Ministry of Food and Drug Safety (MFDS)
Brazil: National Health Surveillance Agency
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
Guatemala: Ministry of Public Health and Social Assistance
India: Ministry of Health
Panama: Ministry of Health
Dominican Republic: Secretaría del Estado de Salud Pública y Asistencia Social (SESPAS)
Ecuador: Public Health Ministry
Greece: National Organization of Medicines
India: Drugs Controller General of India
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Portugal: National Pharmacy and Medicines Institute
South Africa: Medicines Control Council

Keywords provided by Novartis:
Rheumatoid Arthritis, RA, IL-17 blocker, subcutaneous, self-injection, AIN457, AIN457F, secukinumab, anti-TNFα, pre-filled syringe

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016