Clinical trial NCT01649375: 16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anklyosing Spondylitis
Keywords: Ankylosing spondylitis
AS
Chronic inflammatory disease
Inflammatory back pain
Secukinumab
Prefilled syringe
PFS
Subcutaneous injection
AIN457
AIN457F
AIN457F2310
adult
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-25
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study assessed the efficacy and safety of secukinumab in patients with active ankylosing spondylitis who were tolerant to or had an inadequate response to NSAIDs, DMARDs and / or TNFα inhibitor


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving ASAS 20 (SpondyloArthritis International Society Criteria) Response at Week 16
timeFrame: Baseline up to 16 weeks
Secondary outcomes:
measure: Percentage of Participants Achieving ASAS 40 (SpondyloArthritis International Society Criteria) Response
timeFrame: Baseline up to 16 weeks
measure: Change From Baseline at Week 16 in Serum hsCRP
timeFrame: Baseline up to 16 weeks
measure: Percentage of Participants Achieving ASAS 5/6 (SpondyloArthritis International Society Criteria) Response at Week 16
timeFrame: Baseline up to 16 weeks
measure: Change From Baseline at Week 16 for Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: Baseline up to 16 weeks
measure: Change From Baseline at Week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)
timeFrame: Baseline up to 16 weeks
measure: Change From Baseline at Week 16 in ASQoL
timeFrame: Baseline up to 16 weeks
measure: Percentage of Participants Achieving ASAS Partial Remission at Week 16
timeFrame: Baseline up to 16 weeks
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Upland
country: United States
facility: Novartis Investigative Site
state: California
city: Edina
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Tupelo
country: United States
facility: Novartis Investigative Site
state: Mississippi
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Duncansville
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: Pointe-Claire
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Bruntal
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: HUS
country: Finland
facility: Novartis Investigative Site
city: Hyvinkaa
country: Finland
facility: Novartis Investigative Site
city: Jyvaskyla
country: Finland
facility: Novartis Investigative Site
city: Seinajoki
country: Finland
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
state: The Netherlands
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Korolev
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Petrozavodsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Fribourg
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Leytonstone
country: United Kingdom
facility: Novartis Investigative Site
state: London
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Norwich
country: United Kingdom
facility: Novartis Investigative Site
city: Torquay
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.