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Efficacy, Safety and Tolerability of Secukinumab in Patients With Rheumatoid Arthritis Taking Methotrexate

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01359943
First received: May 19, 2011
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

The study compared the efficacy and assessed the safety of secukinumab given as 3 intravenous (i.v.) loading doses or weekly sub-cutaneous (s.c.) loading doses, compared to placebo, followed by monthly s.c. injections in patients with active Rheumatoid Arthritis (RA) despite treatment with Methotrexate.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: secukinumab (AIN457)
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study of Efficacy, Safety and Tolerability of Secukinumab at 12 Weeks Administered With an Intravenous (i.v.) or Subcutaneous (s.c.) Loading Regimen Compared to Placebo in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of participants who achieve American College of Rheumatology Response of 20 (ACR20) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).


Secondary Outcome Measures:
  • Percentage of participants who achieve ACR50 and ACR70 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).

  • Change from baseline in Disease Activity Score 28 response using ESR (DAS28-ESR) [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), erythrocyte sedimentation rate (ESR), and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = very good and 100 = very bad ). Using the data from these variables, DAS28-ESR is calculated using the following formula: DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH. The calculation results in a DAS28-ESR score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

  • Change from baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) score. [ Time Frame: baseline, 12 Weeks ] [ Designated as safety issue: No ]
    The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. Then the HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. The HAQ score is not computed if the patient does not have scores for at least 6 categories. The HAQ score ranges from 0 (without any difficulty) to 3 (unable to do).

  • Percentage of participants with European League Against Rheumatism (EULAR) response [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    EULAR response criteria are based on DAS28 status in combination with DAS28 improvements. The EULAR response criteria are as follows: present DAS28 <3.2 with DAS28 improvement >1.2 corresponds to 'good response'; present DAS28 <3.2 with DAS28 improvement between 0.6 to 1.2, or present DAS28 between 3.2 to 5.1 with DAS28 improvement from 0.6 to >1.2, or present DAS28 >5.2 with DAS28 improvement >1.2 correspond to 'moderate response; present DAS28 <3.2 with DAS28 improvement <0.6, or present DAS28 between 3.2 to 5.1 with DAS28 improvement <0.6, or present DAS28 >5.1 with DAS28 improvement <0.6 to 1.2 correspond to 'no response'.

  • Change from baseline in tender 68-joint count [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The 68 joints assessed for tenderness included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0).

  • Change from baseline in participant's assessment of rheumatoid arthritis (RA) pain [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The patient's assessment of pain was performed using 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (unbearable pain) after the question "Please indicate with a vertical mark through the horizontal line the most pain you had from your rheumatoid arthritis over the last 24 hours".

  • Change from baseline in participant's global assessment of disease activity [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question "Considering all the ways rheumatoid arthritis affects you, please indicate with a vertical mark through the horizontal line how well you are doing today".

  • Change from baseline in hsCRP [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    Blood for this assessment was obtained to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.

  • Change from baseline in ESR [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    Blood for this assessment was obtained to monitor disease activity and response to therapy.

  • Change from baseline in DAS28 using high sensitivity C-reactive protein (hsCRP) (DAS28-CRP) [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28-CRP is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-CRP is calculated using the following formula: DAS28-4(crp) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. The calculation results in a DAS28-CRP score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

  • Change from baseline in swollen 66-joint count [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The 66 joints assessed for swelling included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0).

  • Change from baseline in physician's global assessment of disease activity [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question "Considering all the ways rheumatoid arthritis affects your patient, how would you rate his or her current condition?"


Enrollment: 221
Study Start Date: October 2011
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: secukinumab 10 mg/kg i.v. loading
secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
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).
Drug: placebo
Matching placebo to AIN457 i.v. and to AIN457 s.c..
Experimental: secukinumab 150 mg s.c. loading
secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8
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).
Drug: placebo
Matching placebo to AIN457 i.v. and to AIN457 s.c..
Placebo Comparator: placebo
placebo at Weeks 0, 1, 2, 3, 4, 8 & 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16
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).
Drug: placebo
Matching placebo to AIN457 i.v. and to AIN457 s.c..

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening
  • must have been taking MTX for at least 3 months before randomization and must currently be on a stable dose of MTX for at least 4 weeks before randomization.
  • At Baseline: Disease activity criteria defined by >6 tender joints out of 68 and >6 swollen joints out of 66 and with at least 1 of the following at screening: Anti-CCP antibodies positive OR Rheumatoid Factor positive and with at least 1 of the following at screening: hsCRP ≥ 10 mg/L OR ESR ≥ 28

Exclusion criteria:

  • RA patients functional status class IV according to the ACR 1991 revised criteria
  • Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
  • Previous exposure ever to an anti-TNF-a agent or any other immunomodulatory biologic agent (experimental or approved)
  • Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, or morphine)
  • Any therapy by intra-articular injections (e.g. corticosteroid, hyaluronan) required for treatment of arthritis within 4 weeks before randomization
  • 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: NCT01359943

  Show 39 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01359943     History of Changes
Other Study ID Numbers: CAIN457F2206, 2010-024516-34
Study First Received: May 19, 2011
Last Updated: November 3, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Hungary: Institutional Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Poland: The Central Register of Clinical Trials
Slovakia: State Institute for Drug Control

Keywords provided by Novartis:
Rheumatoid Arthritis
RA
secukinumab
AIN457
inflammatory joints
American College of Rheumatology
ACR

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Antibodies, Monoclonal
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014