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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 (REASSURE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01377012
First received: June 17, 2011
Last updated: February 9, 2017
Last verified: February 2017
  Purpose
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.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Core Study: Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20) at Week 24 [ Time Frame: Week 24 ]
    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.

  • Extension Phase: Percentage of Patients Achieving a American College of Rheumatology Response ACR20, ACR50 and ACR70 [ Time Frame: up to week 260 ]

Secondary Outcome Measures:
  • Core Study: Change From Baseline and Week 24 in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 24 ]
    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.

  • Core Study: Change From Baseline at Week 24 in Van Der Heijde Total Modified Sharp Score [ Time Frame: Week 24 ]
    Separate radiographs of each hand/wrist and each foot were taken at basline and Week 24. The radiographs were assessed using the van der Heijde modified Sharp score. The change in the Van der Heijde modified Sharp score is calculated against the baseline value. The total van der Heide modified Sharp score goes from 0 to 448, the bigger the change, the worse it is for the patient.

  • Core Study Percentage of Patients Achieving Major Clinical Response (Continuous Six-month Period of ACR70 Response During the 1 Year Period) at Week 52 [ Time Frame: 52 week ]
    The major clinical response is defined as continuous six-month period of ACR70 response during the 1 year period. ACR70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 70% 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 ACR70 response results at week 24 used non-responder imputation.

  • Extension Phase: Change in Baseline of RA Disease Activity as Measured by Disease Activity Score (DAS28) [ Time Frame: week 260 ]

    The DAS28 score is a measure of RA disease activity calculated using variables such as swollen joint count, the Erythrocyte Sedimentation Rate (ESR) and patient reported assessment of health.

    Using this data, the DAS28 calculation provides a number on a scale from 0-10 indicating the current activity of a patient's RA. A DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 score lower than 2.6.


  • Extension Phase: Proportion of Subjects Achieving Low Disease Activity and Good/Moderate European League Against Rheumatism (EULAR) Responses [ Time Frame: up to week 260 ]
    Low Disease Activity is defined as DAS28 ≤ 3.2. EULAR good response requires an improvement of > 1.2 in the DAS28 score with a present score of ≤3.2; EULAR moderate response is defined as an improvement of >0.6 to ≤1.2 in DAS28 and a present score of ≤5.1; or an improvement of >1.2 and a present score of >3.2.

  • Extension Phase: Proportion of Subjects Achieving ACR/(EULAR) Remission [ Time Frame: up to week 260 ]
    ACR/EULAR remission is defined as SDAI ≤ 3.3, where SDAI is a measure of disease activity in RA based on 28 tender and swollen joint counts, CRP, Physician and Patient's Global Assessments of Disease

  • Extension Phase: Changes in Baseline of Quality of Life (Qol) Outcomes Measured by Medical Outcome Short Form SF-36 v2 [ Time Frame: Baseline, up to week 260 ]
    Short Form Health Survey (SF-36) consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed.

  • Extension Phase: Immunogenicity Against Secukinumab [ Time Frame: up to week 260 ]

Enrollment: 637
Actual Study Start Date: August 30, 2011
Study Completion Date: September 9, 2015
Primary Completion Date: September 9, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AIN457 10mg/kg-75mg
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks
Biological: Secukinumab (AIN457)
AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL- 17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.
Other Name: AIN457
Experimental: AIN457 10mg/kg-150mg
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks
Biological: Secukinumab (AIN457)
AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL- 17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.
Other Name: AIN457
Placebo Comparator: Placebo
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24
Biological: Placebo
Placebo was given as i.v. at baseline, week 2 and week 4, and then s.c. every 4 weeks starting at week 8.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  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: NCT01377012

  Show 141 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01377012     History of Changes
Other Study ID Numbers: CAIN457F2302/E1
2011-000275-13 ( EudraCT Number )
Study First Received: June 17, 2011
Results First Received: May 24, 2016
Last Updated: February 9, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Rheumatoid Arthritis
RA
ACR
inflammatory joints

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 June 23, 2017