Trial from ClinicalTrials.gov

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Trial ID
NCT02159053
Ethics application status
Date submitted
28/02/2014
Date registered
28/02/2014
Date last updated
21/09/2016

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
Assessment of Spondyloarthritis International Society criteria / ASAS 20 - ASAS 20 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 20% improvement in score in at least 3 of a conventional set of 4 clinical domains relevant to AS and no worsening in the fourth domain. In this study, ASAS 20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo
Timepoint [1] 0 0
16 weeks
Secondary outcome [1] 0 0
ASAS 40 response - ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 40% improvement in score in at least 3 of a conventional set of 4 clinical domains relevant to AS and no worsening in the fourth domain. In this study, ASAS 40 is used to assess the efficacy of secukinumab, with or without loading, versus placebo.
Timepoint [1] 0 0
16 weeks
Secondary outcome [2] 0 0
Serum hsCRP - Blood levels of C-reactive protein (CRP), an acute phase reactant, are indicative of inflammation and of its severity, and can be used to monitor treatment response. A high sensitivity CRP (hsCRP) test is implemented in this study, to assess the efficacy of secukinumab, with or without loading, versus placebo in reducing AS elicited systemic inflammation over the time
Timepoint [2] 0 0
16 weeks
Secondary outcome [3] 0 0
ASAS 5/6 response - ASAS 5/6 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevant to AS and no worsening in the remaining domain. In this study, ASAS 5/6 is used to assess the efficacy of secukinumab, with or without loading, versus placebo.
Timepoint [3] 0 0
16 weeks
Secondary outcome [4] 0 0
Bath Ankylosing Spondylitis Disease Activity Index / BASDAI - BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem"), to characterise six clinical domains pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, the BASDAI index is used to assess the efficacy of secukinumab, with or without loading, versus placebo.
Timepoint [4] 0 0
16 weeks
Secondary outcome [5] 0 0
Short Form-36 Physical Component Summary (SF-36 PCS) health survey - The SF-36-PCS is used to assess improvement from baseline of secukinumab, with or without loading, versus placebo. SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed.
Timepoint [5] 0 0
16 weeks
Secondary outcome [6] 0 0
Ankylosing Spondylitis Quality of Life (ASQoL) - ASQoL is an 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 participant with AS: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). In this study, ASQoL is used to assess improvement from baseline secukinumab, with or without loading, versus placebo
Timepoint [6] 0 0
16 weeks
Secondary outcome [7] 0 0
Overall safety and tolerability - These assessments will be implemented in terms of physical examination and vital signs outcomes, clinical laboratory results, nature and frequency of the observed adverse events and serious adverse events, frequency and severity of any injection site reactions, ECG outcomes and the detection of immunogenicity. During the first 16 weeks of the study, comparisons between the secukinumab treatment arms and the placebo treatment arm will also take place.
Timepoint [7] 0 0
112 weeks

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
Active, not recruiting
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
Current
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
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
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
California
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United States of America
State/province [3] 0 0
Florida
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United States of America
State/province [4] 0 0
Illinois
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United States of America
State/province [5] 0 0
Louisiana
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United States of America
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Nebraska
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United States of America
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New Jersey
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United States of America
State/province [8] 0 0
Oklahoma
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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Texas
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United States of America
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Washington
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Austria
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Graz
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Austria
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Vienna
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Austria
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Wien
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Bulgaria
State/province [16] 0 0
Pleven
Country [17] 0 0
Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Bulgaria
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Targovishte
Country [20] 0 0
Canada
State/province [20] 0 0
Manitoba
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Czech Republic
State/province [22] 0 0
Ostrava
Country [23] 0 0
Czech Republic
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Praha 11
Country [24] 0 0
Czech Republic
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Praha 2
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Czech Republic
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Uherske Hradiste
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Denmark
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Frederiksberg
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Denmark
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Odense
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Finland
State/province [28] 0 0
Hyvinkää
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Finland
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Jyvaskyla
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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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Goettingen
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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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München
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Germany
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Würzburg
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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
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MI
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Italy
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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 2333 ZA
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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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Slovak Republic
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Slovakia
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Partizánske
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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
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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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Madrid
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Spain
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Vizcaya
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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 [75] 0 0
Doncaster
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United Kingdom
State/province [76] 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
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
Contact person responsible for updating information