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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02159053




Registration number
NCT02159053
Ethics application status
Date submitted
28/02/2014
Date registered
9/06/2014
Date last updated
10/04/2019

Titles & IDs
Public title
16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Ankylosing Spondylitis
Scientific 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
Secondary ID [1] 0 0
2013-005575-41
Secondary ID [2] 0 0
CAIN457F2320
Universal Trial Number (UTN)
Trial acronym
MEASURE4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spondylitis, Ankylosing 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Secukinumab
Other interventions - Secukinumab
Other interventions - Placebo

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.

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.

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.


Other interventions: Secukinumab
Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio

Other interventions: Secukinumab
Eligible subjects are randomized to each of the three treatment arms in 1:1:1 ratio

Other interventions: Placebo
Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Responded for Assessment of Spondyloarthritis International Society 20 Criteria (ASAS20) at 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)
Timepoint [1] 0 0
16 Weeks
Secondary outcome [1] 0 0
Percentage of Participants Responded for ASAS 40 Response at 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:
Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
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
Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).
Timepoint [1] 0 0
16 Weeks
Secondary outcome [2] 0 0
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at 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.
Timepoint [2] 0 0
Baseline, 16 Weeks
Secondary outcome [3] 0 0
Percentage of Participants Responded for ASAS 5/6 Response at 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:
Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale
Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem)
Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment
C-reactive protein (CRP, acute phase reactant).
Timepoint [3] 0 0
16 Weeks
Secondary outcome [4] 0 0
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 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:
Fatigue
Spinal pain
Joint pain / swelling
Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments)
Morning stiffness duration
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.
Timepoint [4] 0 0
Baseline, 16 Weeks
Secondary outcome [5] 0 0
Change From Baseline in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36) - 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.
Timepoint [5] 0 0
Baseline, 16 Weeks
Secondary outcome [6] 0 0
Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at 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).
Timepoint [6] 0 0
Baseline, 16 Weeks
Secondary outcome [7] 0 0
Number of Participants With Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs) and Related Discontinuations at 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.
Timepoint [7] 0 0
104 Weeks
Secondary outcome [8] 0 0
Percentage of Participants Responded for ASAS 20 at 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:
Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
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
Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).
Timepoint [8] 0 0
Week 4
Secondary outcome [9] 0 0
Percentage of Participants Responded for ASAS 40 Response at 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:
Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe
Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain
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
Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).
Timepoint [9] 0 0
Week 4

Eligibility
Key inclusion criteria
Inclusion criteria: moderate to severe AS, prior radiographic evidence according to the
Modified NY Criteria (1984), inadequate response to NSAIDs.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [2] 0 0
Novartis Investigative Site - Maroochydore
Recruitment hospital [3] 0 0
Novartis Investigative Site - Hobart
Recruitment hospital [4] 0 0
Novartis Investigative Site - Malvern East
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4558 - Maroochydore
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3145 - Malvern East
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Austria
State/province [13] 0 0
Graz
Country [14] 0 0
Austria
State/province [14] 0 0
Vienna
Country [15] 0 0
Bulgaria
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Pleven
Country [16] 0 0
Bulgaria
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Plovdiv
Country [17] 0 0
Bulgaria
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Sofia
Country [18] 0 0
Bulgaria
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Targovishte
Country [19] 0 0
Canada
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Manitoba
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Canada
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Quebec
Country [21] 0 0
Czechia
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Czech Republic
Country [22] 0 0
Denmark
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Frederiksberg
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Denmark
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Odense
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Finland
State/province [24] 0 0
Hyvinkaa
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Finland
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Jyvaskyla
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Germany
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Lower Saxony
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Germany
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Bad Doberan
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Germany
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Berlin
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Germany
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Chemnitz
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Germany
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Erlangen
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Germany
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Germering
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Germany
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Hamburg
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Germany
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Herne
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Germany
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Leipzig
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Germany
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Magdeburg
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Germany
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Muenchen
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Germany
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Wurzburg
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Greece
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Athens
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Greece
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Patras
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Italy
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GE
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Italy
State/province [41] 0 0
MI
Country [42] 0 0
Italy
State/province [42] 0 0
TO
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Italy
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VR
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Netherlands
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Amsterdam
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Netherlands
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Heerlen
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Netherlands
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Leiden
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Netherlands
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Rotterdam
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Norway
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Kongsvinger
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Poland
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Bialystok
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Poland
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Elblag
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Poland
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Poznan
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Poland
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Warszawa
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Russian Federation
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Barnaul
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Russian Federation
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Kemerovo
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Russian Federation
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S.-Petersburg
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Russian Federation
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Saint Petersburg
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Russian Federation
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St-Petersburg
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Slovakia
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SVK
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Slovakia
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Partizanske
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Slovakia
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Sabinov
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Slovakia
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Stara Lubovna
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Slovakia
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Topolcany
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Spain
State/province [63] 0 0
Andalucia
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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Galicia
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Spain
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Vizcaya
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Spain
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Madrid
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Switzerland
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Fribourg
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Switzerland
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St Gallen
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United Kingdom
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London
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United Kingdom
State/province [72] 0 0
Doncaster
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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-TNFa therapy.
Trial website
https://clinicaltrials.gov/show/NCT02159053
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications