16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis

NCT01649375 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CAIN457F23102012-000046-35
• Study Type: interventional
• Target: 219
• Locations: 13 countries
• Sites: 53

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

Conditions

Anklyosing Spondylitis

Keywords

Ankylosing spondylitis; AS; Chronic inflammatory disease; Inflammatory back pain; Secukinumab; Prefilled syringe; PFS; Subcutaneous injection; AIN457; AIN457F; AIN457F2310; adult

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving ASAS 20 (SpondyloArthritis International Society Criteria) Response at Week 16

  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.

  Baseline up to 16 weeks

Secondary Outcomes (7)

• Percentage of Participants Achieving ASAS 40 (SpondyloArthritis International Society Criteria) Response

  Baseline up to 16 weeks

• Change From Baseline at Week 16 in Serum hsCRP

  Baseline up to 16 weeks

• Percentage of Participants Achieving ASAS 5/6 (SpondyloArthritis International Society Criteria) Response at Week 16

  Baseline up to 16 weeks

• Change From Baseline at Week 16 for Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

  Baseline up to 16 weeks

• Change From Baseline at Week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)

  Baseline up to 16 weeks

Study Arms (3)

Secukinumab 75 mg

EXPERIMENTAL

Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.

Drug: Secukinumab (75 mg)

Secukinumab 150 mg

EXPERIMENTAL

Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks

Drug: Secukinumab (150 mg)

Placebo

PLACEBO COMPARATOR

Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks

Drug: Placebo

Interventions

Secukinumab (75 mg) DRUG

Secukinumab 75 mg s.c.

Also known as: AIN457 75 mg

Secukinumab 75 mg

Placebo DRUG

Placebo

Placebo

Secukinumab (150 mg) DRUG

Secukinumab 150 mg s.c.

Also known as: AIN457 150 mg

Secukinumab 150 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (53)

Novartis Investigative Site

Mesa, Arizona, 85202, United States

Location

Novartis Investigative Site

Upland, California, 91786, United States

Location

Novartis Investigative Site

Edina, Minnesota, 55435, United States

Location

Novartis Investigative Site

Tupelo, Mississippi, 38801, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73102, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73103, United States

Location

Novartis Investigative Site

Duncansville, Pennsylvania, 16635, United States

Location

Novartis Investigative Site

Charleston, South Carolina, 29460, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37909, United States

Location

Novartis Investigative Site

Mesquite, Texas, 75150, United States

Location

Novartis Investigative Site

Graz, 8036, Austria

Location

Novartis Investigative Site

Vienna, 1100, Austria

Location

Novartis Investigative Site

Winnipeg, Manitoba, R3A 1M3, Canada

Location

Novartis Investigative Site

Pointe-Claire, Quebec, H9R 3J1, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1W 4R4, Canada

Location

Novartis Investigative Site

Sainte-Foy, Quebec, G1V 3M7, Canada

Location

Novartis Investigative Site

Bruntál, Czech Republic, 792 01, Czechia

Location

Novartis Investigative Site

Ostrava, Czech Republic, 772 00, Czechia

Location

Novartis Investigative Site

Prague, Czech Republic, 128 50, Czechia

Location

Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

Location

Novartis Investigative Site

HUS, Finland, 00029, Finland

Location

Novartis Investigative Site

Helsinki, FI 00100, Finland

Location

Novartis Investigative Site

Hyvinkää, 05800, Finland

Location

Novartis Investigative Site

Jyväskylä, 40620, Finland

Location

Novartis Investigative Site

Seinäjoki, 60200, Finland

Location

Novartis Investigative Site

Berlin, 12203, Germany

Location

Novartis Investigative Site

Herne, 44649, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Catania, CT, 95100, Italy

Location

Novartis Investigative Site

Torino, TO, 10128, Italy

Location

Novartis Investigative Site

Verona, VR, 37134, Italy

Location

Novartis Investigative Site

Utrecht, The Netherlands, 3508 GA, Netherlands

Location

Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Korolyov, 141060, Russia

Location

Novartis Investigative Site

Moscow, 115522, Russia

Location

Novartis Investigative Site

Petrozavodsk, 185019, Russia

Location

Novartis Investigative Site

Saint Petersburg, 190068, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Yaroslavl, 150003, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620028, Russia

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

Location

Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Fribourg, 1708, Switzerland

Location

Novartis Investigative Site

Zurich, CH 8091, Switzerland

Location

Novartis Investigative Site

Leytonstone, London, E11 1NR, United Kingdom

Location

Novartis Investigative Site

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

Novartis Investigative Site

Norwich, NR4 7UY, United Kingdom

Location

Novartis Investigative Site

Torquay, TQ2 7AA, United Kingdom

Location

Related Publications (14)

• Marzo-Ortega H, Sieper J, Kivitz AJ, Blanco R, Cohen M, Pavelka K, Delicha EM, Stefanska A, Richards HB, Rohrer S. 5-year efficacy and safety of secukinumab in patients with ankylosing spondylitis: end-of-study results from the phase 3 MEASURE 2 trial. Lancet Rheumatol. 2020 Jun;2(6):e339-e346. doi: 10.1016/S2665-9913(20)30066-7.

  PMID: 38273597 DERIVED

• 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.

  PMID: 34773130 DERIVED

• 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.

  PMID: 34618347 DERIVED

• 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.

  PMID: 33722947 DERIVED

• 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.

  PMID: 33351179 DERIVED

• 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.

  PMID: 33252266 DERIVED

• 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.

  PMID: 33227175 DERIVED

• 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.

  PMID: 32352653 DERIVED

• 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.

  PMID: 31203228 DERIVED

• 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.

  PMID: 30564451 DERIVED

• 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.

  PMID: 28544533 DERIVED

• 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.

  PMID: 28235249 DERIVED

• 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.

  PMID: 27582421 DERIVED

• 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.

  PMID: 26699169 DERIVED

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2012
• First Posted: July 25, 2012
• Study Start: October 18, 2012
• Primary Completion: August 4, 2014
• Study Completion: September 18, 2018
• Last Updated: October 30, 2019
• Results First Posted: October 30, 2019

Record last verified: 2019-10

Locations

US (10); SG (2); ES (4); CZ (4); NL (2); CH (3); RU (7); GB (4); IT (3); AU (2); FI (5); DE (3); CA (4)