- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01649375
16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis (MEASURE2)
A Randomized, Double-blind, Placebo-controlled Phase III Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate Efficacy at 16 Weeks and to Assess Long-term Efficacy, Safety and Tolerability up to 5 Years in Patients With Active Ankylosing Spondylitis
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Graz, Austria, 8036
- Novartis Investigative Site
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Vienna, Austria, 1100
- Novartis Investigative Site
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Quebec, Canada, G1W 4R4
- Novartis Investigative Site
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Manitoba
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Winnipeg, Manitoba, Canada, R3A 1M3
- Novartis Investigative Site
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Quebec
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Pointe-Claire, Quebec, Canada, H9R 3J1
- Novartis Investigative Site
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Sainte-Foy, Quebec, Canada, G1v 3M7
- Novartis Investigative Site
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Uherske Hradiste, Czechia, 686 01
- Novartis Investigative Site
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Czech Republic
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Bruntal, Czech Republic, Czechia, 792 01
- Novartis Investigative Site
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Ostrava, Czech Republic, Czechia, 772 00
- Novartis Investigative Site
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Praha 2, Czech Republic, Czechia, 128 50
- Novartis Investigative Site
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HUS, Finland, 00029
- Novartis Investigative Site
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Helsinki, Finland, FI 00100
- Novartis Investigative Site
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Hyvinkaa, Finland, 05800
- Novartis Investigative Site
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Jyvaskyla, Finland, 40620
- Novartis Investigative Site
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Seinajoki, Finland, 60200
- Novartis Investigative Site
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Berlin, Germany, 12203
- Novartis Investigative Site
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Herne, Germany, 44649
- Novartis Investigative Site
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Wuerzburg, Germany, 97080
- Novartis Investigative Site
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CT
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Catania, CT, Italy, 95100
- Novartis Investigative Site
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TO
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Torino, TO, Italy, 10128
- Novartis Investigative Site
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VR
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Verona, VR, Italy, 37134
- Novartis Investigative Site
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Amsterdam, Netherlands, 1105 AZ
- Novartis Investigative Site
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The Netherlands
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Utrecht, The Netherlands, Netherlands, 3508 GA
- Novartis Investigative Site
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Ekaterinburg, Russian Federation, 620028
- Novartis Investigative Site
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Korolev, Russian Federation, 141060
- Novartis Investigative Site
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Moscow, Russian Federation, 115522
- Novartis Investigative Site
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Petrozavodsk, Russian Federation, 185019
- Novartis Investigative Site
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Saint Petersburg, Russian Federation, 197022
- Novartis Investigative Site
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St Petersburg, Russian Federation, 190068
- Novartis Investigative Site
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Yaroslavl, Russian Federation, 150003
- Novartis Investigative Site
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Singapore, Singapore, 119074
- Novartis Investigative Site
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Singapore, Singapore, 169608
- Novartis Investigative Site
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Madrid, Spain, 28046
- Novartis Investigative Site
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Madrid, Spain, 28009
- Novartis Investigative Site
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Cantabria
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Santander, Cantabria, Spain, 39008
- Novartis Investigative Site
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Galicia
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La Coruna, Galicia, Spain, 15006
- Novartis Investigative Site
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Basel, Switzerland, 4031
- Novartis Investigative Site
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Fribourg, Switzerland, 1708
- Novartis Investigative Site
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Zuerich, Switzerland, CH 8091
- Novartis Investigative Site
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Norwich, United Kingdom, NR4 7UY
- Novartis Investigative Site
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Torquay, United Kingdom, TQ2 7AA
- Novartis Investigative Site
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London
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Leytonstone, London, United Kingdom, E11 1NR
- Novartis Investigative Site
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West Yorkshire
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Leeds, West Yorkshire, United Kingdom, LS7 4SA
- Novartis Investigative Site
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Arizona
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Mesa, Arizona, United States, 85202
- Novartis Investigative Site
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California
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Upland, California, United States, 91786
- Novartis Investigative Site
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Minnesota
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Edina, Minnesota, United States, 55435
- Novartis Investigative Site
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Mississippi
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Tupelo, Mississippi, United States, 38801
- Novartis Investigative Site
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73103
- Novartis Investigative Site
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Oklahoma City, Oklahoma, United States, 73102
- Novartis Investigative Site
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Pennsylvania
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Duncansville, Pennsylvania, United States, 16635
- Novartis Investigative Site
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South Carolina
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Charleston, South Carolina, United States, 29460
- Novartis Investigative Site
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Tennessee
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Knoxville, Tennessee, United States, 37909
- Novartis Investigative Site
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Texas
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Mesquite, Texas, United States, 75150
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or non-pregnant, non-lactating female patients
- Diagnosis of moderate to severe AS with prior documented radiologic evidence (x-ray) fulfilling the Modified New York criteria for AS (1984)
- Patients should have been on NSAIDs with an inadequate response
- Patients who were regularly taking NSAIDs as part of their AS therapy are required to be on a stable dose
- Patients who had been on an anti-TNFα agent (not more than one) must have experienced an inadequate response
Exclusion Criteria:
- Chest X-ray (or MRI) with evidence of ongoing infectious or malignant process
- Patients with total ankylosis of the spine
- Patients previously treated with any biological immunomodulating agents except for those targeting TNFα
- Previous treatment with any cell-depleting therapies
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Secukinumab 75 mg
Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.
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Secukinumab 75 mg s.c.
Other Names:
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EXPERIMENTAL: Secukinumab 150 mg
Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks
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Secukinumab 150 mg s.c.
Other Names:
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PLACEBO_COMPARATOR: Placebo
Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks
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Placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants Achieving ASAS 20 (SpondyloArthritis International Society Criteria) Response at Week 16
Time Frame: Baseline up to 16 weeks
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ASAS 20 response is a validated composite assessment reflecting the percentage of treated patients who achieve within a defined timeframe an improvement of 20% and ≥1 unit on a scale of 1 to 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit in the remaining domain.
ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.
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Baseline up to 16 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants Achieving ASAS 40 (SpondyloArthritis International Society Criteria) Response
Time Frame: Baseline up to 16 weeks
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ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe an improvement of ≥40% and ≥2 units on a scale of 0 to 10 (0 being worse and 10 being better) in at least three of the four ASAS main domains (patient global, pain, function and inflammation) and no worsening at all in the remaining domain. ASAS 40 is used to assess the efficacy of at least one dose of secukinumab against placebo. |
Baseline up to 16 weeks
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Change From Baseline at Week 16 in Serum hsCRP
Time Frame: Baseline up to 16 weeks
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The change from baseline in hsCRP is expressed as a ratio of post-baseline to baseline values.
With the ratio normalized to 1.0 at baseline, ratios less than 1.0 represent decreased post-baseline values, whereas ratios greater than 1.0 represent increased post-baseline values.
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 sensitvity CRP (hsCRP) test is implemented in this study to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over time.
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Baseline up to 16 weeks
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Percentage of Participants Achieving ASAS 5/6 (SpondyloArthritis International Society Criteria) Response at Week 16
Time Frame: Baseline up to 16 weeks
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ASAS 5/6 response is a validated composite assessment, reflecting the percentage of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevant to AS (pain, patient global assessment, function, inflammation, spinal mobility, C-reative protein) without deterioration in the 6th domain.
In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab against placebo.
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Baseline up to 16 weeks
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Change From Baseline at Week 16 for Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Time Frame: Baseline up to 16 weeks
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BASDAI is a validated assessment tool using 1 through 10 scales (1 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains (fatigue, spinal pain, joint pain/selling, localized tenderness, morning stiffness duration, morning stiffness severity) 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 is used to assess the efficacy of at least one dose of secukinumab verus placebo.
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Baseline up to 16 weeks
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Change From Baseline at Week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)
Time Frame: Baseline up to 16 weeks
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Physical Function Component Summary (PCS) is only 1 component of SF-36.
This scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight.
The lower the score the more disability.
The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
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Baseline up to 16 weeks
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Change From Baseline at Week 16 in ASQoL
Time Frame: Baseline up to 16 weeks
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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 of at least one dose of secukinumab versus placebo.
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Baseline up to 16 weeks
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Percentage of Participants Achieving ASAS Partial Remission at Week 16
Time Frame: Baseline up to 16 weeks
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ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale 0 to 10.
In this study ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.
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Baseline up to 16 weeks
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Dougados M, Kiltz U, Kivitz A, Pavelka K, Rohrer S, McCreddin S, Quebe-Fehling E, Porter B, Talloczy Z. Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials. Rheumatol Int. 2022 Feb;42(2):205-213. doi: 10.1007/s00296-021-05044-6. Epub 2021 Nov 13.
- van der Horst-Bruinsma I, Miceli-Richard C, Braun J, Marzo-Ortega H, Pavelka K, Kivitz AJ, Deodhar A, Bao W, Porter B, Pournara E. A Pooled Analysis Reporting the Efficacy and Safety of Secukinumab in Male and Female Patients with Ankylosing Spondylitis. Rheumatol Ther. 2021 Dec;8(4):1775-1787. doi: 10.1007/s40744-021-00380-2. Epub 2021 Oct 7.
- Schett G, Baraliakos X, Van den Bosch F, Deodhar A, Ostergaard M, Gupta AD, Mpofu S, Fox T, Winseck A, Porter B, Shete A, Gensler LS. Secukinumab Efficacy on Enthesitis in Patients With Ankylosing Spondylitis: Pooled Analysis of Four Pivotal Phase III Studies. J Rheumatol. 2021 Aug;48(8):1251-1258. doi: 10.3899/jrheum.201111. Epub 2021 Mar 15.
- Baraliakos X, Van den Bosch F, Machado PM, Gensler LS, Marzo-Ortega H, Sherif B, Quebe-Fehling E, Porter B, Gaillez C, Deodhar A. Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies. Rheumatol Ther. 2021 Mar;8(1):273-288. doi: 10.1007/s40744-020-00269-6. Epub 2020 Dec 22.
- Himmler S, Branner JC, Ostwald DA. The societal impact of a biologic treatment of ankylosing spondylitis: a case study based on secukinumab. J Comp Eff Res. 2021 Feb;10(2):143-155. doi: 10.2217/cer-2020-0077. Epub 2020 Nov 30.
- Kvien TK, Conaghan PG, Gossec L, Strand V, Ostergaard M, Poddubnyy D, Williams N, Porter B, Shete A, Gilloteau I, Deodhar A. Secukinumab and Sustained Reduction in Fatigue in Patients With Ankylosing Spondylitis: Long-Term Results of Two Phase III Randomized Controlled Trials. Arthritis Care Res (Hoboken). 2022 May;74(5):759-767. doi: 10.1002/acr.24517. Epub 2022 Mar 10.
- Deodhar AA, Miceli-Richard C, Baraliakos X, Marzo-Ortega H, Gladman DD, Blanco R, Das Gupta A, Martin R, Safi J Jr, Porter B, Shete A, Rosenbaum JT. Incidence of Uveitis in Secukinumab-treated Patients With Ankylosing Spondylitis: Pooled Data Analysis From Three Phase 3 Studies. ACR Open Rheumatol. 2020 May;2(5):294-299. doi: 10.1002/acr2.11139. Epub 2020 Apr 30.
- Deodhar A, Gladman DD, McInnes IB, Spindeldreher S, Martin R, Pricop L, Porter B, Safi J Jr, Shete A, Bruin G. Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis. J Rheumatol. 2020 Apr;47(4):539-547. doi: 10.3899/jrheum.190116. Epub 2019 Jun 15.
- Braun J, Deodhar A, Landewe R, Baraliakos X, Miceli-Richard C, Sieper J, Quebe-Fehling E, Martin R, Porter B, Gandhi KK, van der Heijde D; MEASURE 1 and MEASURE 2 study groups. Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies. RMD Open. 2018 Nov 21;4(2):e000749. doi: 10.1136/rmdopen-2018-000749. eCollection 2018.
- Wei JC, Baeten D, Sieper J, Deodhar A, Bhosekar V, Martin R, Porter B. Efficacy and safety of secukinumab in Asian patients with active ankylosing spondylitis: 52-week pooled results from two phase 3 studies. Int J Rheum Dis. 2017 May;20(5):589-596. doi: 10.1111/1756-185X.13094. Epub 2017 May 25. Erratum In: Int J Rheum Dis. 2017 Jul;20(7):911.
- Marzo-Ortega H, Sieper J, Kivitz A, Blanco R, Cohen M, Martin R, Readie A, Richards HB, Porter B; Measure 2 Study Group. Secukinumab and Sustained Improvement in Signs and Symptoms of Patients With Active Ankylosing Spondylitis Through Two Years: Results From a Phase III Study. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1020-1029. doi: 10.1002/acr.23233. Epub 2017 Jun 7.
- Sieper J, Deodhar A, Marzo-Ortega H, Aelion JA, Blanco R, Jui-Cheng T, Andersson M, Porter B, Richards HB; MEASURE 2 Study Group. Secukinumab efficacy in anti-TNF-naive and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study. Ann Rheum Dis. 2017 Mar;76(3):571-592. doi: 10.1136/annrheumdis-2016-210023. Epub 2016 Aug 31.
- Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M, Mpofu S, Richards HB; MEASURE 1 Study Group; MEASURE 2 Study Group. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015 Dec 24;373(26):2534-48. doi: 10.1056/NEJMoa1505066.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CAIN457F2310
- 2012-000046-35 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD 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
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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