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16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Ankylosing Spondylitis (MEASURE4)

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ClinicalTrials.gov Identifier: NCT02159053
Recruitment Status : Completed
First Posted : June 9, 2014
Results First Posted : April 10, 2019
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to provide 16-week efficacy, safety and tolerability data versus placebo to support the use of secukinumab 150 mg by subcutaneous (s.c.) self-administration with or without a loading regimen and maintenance dosing using pre-filled syringe (PFS) and to assess efficacy, safety and tolerability up to 2 years in subjects with active AS despite current or previous NSAID, non-biologic DMARD, or biologic anti-TNFα therapy.

Condition or disease Intervention/treatment Phase
Spondylitis, Ankylosing Biological: Secukinumab Biological: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Phase III Multicenter Study of Subcutaneous Secukinumab (150 mg) With and Without a Subcutaneous Loading Regimen to Assess Efficacy, Safety, and Tolerability up to 2 Years in Patients With Active Ankylosing Spondylitis
Actual Study Start Date : May 18, 2015
Actual Primary Completion Date : February 23, 2016
Actual Study Completion Date : January 2, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: Secukinumab 150 mg s.c. with loading
Secukinumab 150 mg at Baseline, Weeks 1, 2, and 3, followed by dosing every four weeks starting at Week 4.
Biological: Secukinumab
Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio
Other Name: Secukinumab (AIN457) 150 mg s.c.

Experimental: Secukinumab 150 mg s.c. without loading
Secukinumab 150 mg at Baseline, followed by dosing every four weeks starting at Week 4, with Placebo at Weeks 1, 2, and 3.
Biological: Secukinumab
Eligible subjects are randomized to each of the three treatment arms in 1:1:1 ratio
Other Name: Secukinumab (AIN457) 150 mg s.c.

Placebo Comparator: Placebo
Placebo at Baseline, Weeks 1, 2, 3, 4, 8, and 12, followed by dosing with Secukinumab 150 mg every four weeks starting at Week 16.
Biological: Placebo
Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio




Primary Outcome Measures :
  1. Percentage of Participants Responded for Assessment of Spondyloarthritis International Society 20 Criteria (ASAS20) at 16 Weeks [ Time Frame: 16 Weeks ]
    ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20 percent (%) and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem)


Secondary Outcome Measures :
  1. Percentage of Participants Responded for ASAS 40 Response at 16 Weeks [ Time Frame: 16 Weeks ]

    ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include:

    1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
    2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
    3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale
    4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).

  2. Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at 16 Weeks [ Time Frame: Baseline, 16 Weeks ]
    Blood levels of C-reactive protein (CRP) is an acute phase reactant, which are indicative of inflammation and of its severity, and can be used to monitor treatment response. A hsCRP test is implemented to assess the efficacy of secukinumab (with or without load) versus placebo in reducing ankylosing spondylitis elicited systemic inflammation over the time.

  3. Percentage of Participants Responded for ASAS 5/6 Response at 16 Weeks [ Time Frame: 16 Weeks ]

    ASAS 5/6 response is a validated composite assessment, defined as an improvement of at least 20% in score in at least 5 of 6 clinical domains relevant to ankylosing spondylitis and no worsening in the remaining domain. ASAS domains includes:

    1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
    2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
    3. Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale
    4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem)
    5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment
    6. C-reactive protein (CRP, acute phase reactant).

  4. Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 16 Weeks [ Time Frame: Baseline, 16 Weeks ]

    BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem" on continuous VAS), to answer 6 questions (clinical domains) pertaining to 5 major symptoms of ankylosing spondylitis. Computed composite scores of 4 or greater indicate suboptimal disease control. BASDAI questions includes:

    1. Fatigue
    2. Spinal pain
    3. Joint pain / swelling
    4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments)
    5. Morning stiffness duration
    6. Morning stiffness severity. Each symptom has equal weighting, the mean of two scores related to morning stiffness was taken (questions 5 and 6). The resulting 0 to 10 score was added to the scores from questions 1-4. The resulting 0 to 50 score was divided by 5 to give a final 0-10 BASDAI score. BASDAI was a quick and simple index taking between 30 seconds and 2 minutes for completion.

  5. Change From Baseline in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36) [ Time Frame: Baseline, 16 Weeks ]
    SF-36 is a 36 item questionnaire which measures Quality of Life across eight subscales that were scored individually: physical functioning, role- physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores are weighted sums of the questions in each section. Scores range from 0-100. Lower scores = more disability, higher scores = less disability. The overall summary scores, SF-36 physical Component Summary (PCS) was used to assess improvement from baseline in the Health-Related Quality Of Life of subjects. The change in SF-36 scores were evaluated using MMRM.

  6. Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at 16 Weeks [ Time Frame: Baseline, 16 Weeks ]
    ASQoL is a self-administered 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a subject with ankylosing spondylitis: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score ranges from 0 (good QoL) to 18 (poor QoL). The change in ASQoL scores was evaluated using a mixed effect repeated measures model (MMRM).

  7. Number of Participants With Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs) and Related Discontinuations at 104 Weeks [ Time Frame: 104 Weeks ]
    AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

  8. Percentage of Participants Responded for ASAS 20 at Week 4 [ Time Frame: Week 4 ]

    ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20% and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include:

    1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
    2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
    3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale
    4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).

  9. Percentage of Participants Responded for ASAS 40 Response at Week 4 [ Time Frame: Week 4 ]

    ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include:

    1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
    2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
    3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale
    4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: moderate to severe AS, prior radiographic evidence according to the Modified NY Criteria (1984), inadequate response to NSAIDs.

Exclusion criteria: pregnancy or lactation, on-going infectious or malignant process on a chest X-ray or MRI, previous exposure to IL-17 or IL-17R targeting therapies, previous exposure to any biological immunomodulating agent excluding TNF antagonists, previous cell depleting therapy.

Other protocol-defined inclusion/exclusion criteria do apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02159053


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02159053    
Other Study ID Numbers: CAIN457F2320
2013-005575-41 ( EudraCT Number )
First Posted: June 9, 2014    Key Record Dates
Results First Posted: April 10, 2019
Last Update Posted: April 10, 2019
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
AIN457, ankylosing spondylitis, chronic inflammatory disease, inflammatory back pain, secukinumab, self-injection
Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs