16-week Efficacy and 3-year Safety, Tolerability and Efficacy of Secukinumab in Active Ankylosing Spondylitis Patients (MEASURE 3)

A Randomized, Double-blind, Placebo-controlled Phase III Study of Secukinumab to Demonstrate the Efficacy at 16 Weeks and to Assess the Long-term Safety, Tolerability and Efficacy up to 3 Years in Subjects With Active Ankylosing Spondylitis

The purpose of this study was to generate 16-week efficacy data, as well as up to 3-year efficacy, safety and tolerability data in subjects with active AS despite current or previous NSAID, DMARD and/or anti-TNF therapy.

Study Overview

• Status: Completed
• Conditions: Spondylitis, Ankylosing
• Intervention / Treatment: Drug: Secukinumab; Drug: Placebo secukinumab

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
• Czechia
  • Praha 2, Czechia, 128 50
    • Novartis Investigative Site
  • Czech Republic
    • Uherske Hradiste, Czech Republic, Czechia, 686 01
      • Novartis Investigative Site
• Germany
  • Bad Doberan, Germany, 18209
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Cottbus, Germany, 03042
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Erlangen, Germany, 91056
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Hamburg, Germany, 22081
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Muenchen, Germany, 81541
    • Novartis Investigative Site
  • Zerbst, Germany, 39261
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • Athens, Greece, 115 21
    • Novartis Investigative Site
  • Heraklion, Greece, 700 13
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 27
      • Novartis Investigative Site
    • Thessaloniki, GR, Greece, 564 29
      • Novartis Investigative Site
• Mexico
  • Baja California
    • Mexicali, Baja California, Mexico, 21100
      • Novartis Investigative Site
  • Coahuila
    • Torreon, Coahuila, Mexico, 27000
      • Novartis Investigative Site
  • MEX
    • Culiacan, MEX, Mexico, 80000
      • Novartis Investigative Site
• Portugal
  • Almada, Portugal, 2801 951
    • Novartis Investigative Site
  • Lisboa, Portugal, 1050-034
    • Novartis Investigative Site
  • Lisboa, Portugal, 1649-035
    • Novartis Investigative Site
  • Lisboa, Portugal, 1349-019
    • Novartis Investigative Site
• Russian Federation
  • Kazan, Russian Federation, 420097
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115522
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 190068
    • Novartis Investigative Site
  • St-Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
• United Kingdom
  • Norwich, United Kingdom, NR4 7UY
    • Novartis Investigative Site
  • Torquay, United Kingdom, TQ2 7AA
    • Novartis Investigative Site
  • England
    • London, England, United Kingdom, E11 1NR
      • Novartis Investigative Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Novartis Investigative Site
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Novartis Investigative Site
    • Peoria, Arizona, United States, 85381
      • Novartis Investigative Site
  • California
    • Upland, California, United States, 91786
      • Novartis Investigative Site
  • Florida
    • Palm Harbor, Florida, United States, 34684
      • Novartis Investigative Site
    • Pembroke Pines, Florida, United States, 33026
      • Novartis Investigative Site
  • New Jersey
    • Passaic, New Jersey, United States, 07055
      • Novartis Investigative Site
  • New York
    • Albany, New York, United States, 12206
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29460
      • Novartis Investigative Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novartis Investigative Site
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria: moderate to severe AS, prior radiographic evidence according to the Modified NY Criteria (1984), inadequate response to NSAIDs. -- 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Secukinumab 10 mg/kg i.v. / 300 mg s.c.; Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.	Drug: Secukinumab; AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17).; Other Names: AIN457
EXPERIMENTAL: Secukinumab 10 mg/kg i.v. / 150 mg s.c.; Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study.	Drug: Secukinumab; AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17).; Other Names: AIN457
PLACEBO_COMPARATOR: Placebo i.v. and s.c.; Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection at weeks 8 and 12. At week 16, patients were re-randomised to one of the active treatment arms, to receive secukinumab s.c. Q4W until the end of the study.	Drug: Placebo secukinumab; Placebo to AIN457 (Secukinumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 20% Improvement in the Assessment of Spondyloarthritis International Society Criteria Scale / ASAS 20 Response	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 was used to assess the efficacy of at least one dose of secukinumab versus placebo.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 was used to assess the efficacy of at least one dose of secukinumab versus placebo.	16 weeks
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 was implemented in this study, to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over the time.	Baseline and 16 weeks
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 was used to assess the efficacy of at least one dose of secukinumab versus placebo.	16 weeks
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 was used to assess the efficacy of at least one dose of secukinumab versus placebo.	Baseline and 16 weeks
Number of Participants With Successful Self-administration (to Measure Usability of Pre-filled Syringe)	Successful self-administration is defined as success in steps P8 (Removed Needle Cap from Safety Syringe), P10 (Pinched the Skin at Injection Site), P11 (Inserted the Needle into Skin), P12 (Held onto the Finger Flange), P13 (Fully Depressed Plunger until End Point), and P14 (Held Plunger Down and Syringe in Place) of the Instructions for Use, as observed by the site staff at applicable visits.	Week 8 and Week 12
Pre-filled Syringe Possible Hazard	The number and percentage of subjects who experience any of the defined possible hazards are summarized, as defined in the Possible Hazard assessment check list and as observed by the site staff at applicable visits.	Week 8 and Week 12
Prefilled Syringe Patient Satisfaction Assessment	The self-injection assessment questionnaire (SIAQ) measures overall patient experience with subcutaneous self-injection at applicable visits. Domain scores ranging from 0 (worst experience) to 10 (best experience) are presented: Feeling about injections, Self-confidence, Satisfaction with self-injection.	Baseline, weeks 8, 12 and 16
ASAS Partial Remission	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 of 10. In this study, ASAS partial remission was used to assess the efficacy of at least one dose of secukinumab versus placebo.	16 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

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.
• 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.
• Merola JF, McInnes IB, Deodhar AA, Dey AK, Adamstein NH, Quebe-Fehling E, Aassi M, Peine M, Mehta NN. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications. Rheumatol Ther. 2022 Jun;9(3):935-955. doi: 10.1007/s40744-022-00434-z. Epub 2022 Mar 19.
• Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H, Pricop L, Andersson M, Readie A, Porter B. Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther. 2017 Dec 22;19(1):285. doi: 10.1186/s13075-017-1490-y.

Helpful Links

• Introduction to clinical trials conducted by Novartis and to results of completed studies, with the aim of increasing the transparency of Novartis clinical research and making publicly available objective scientific information in a standardised format.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2014
• Primary Completion (ACTUAL): February 23, 2015
• Study Completion (ACTUAL): December 11, 2017

Study Registration Dates

• First Submitted: December 8, 2013
• First Submitted That Met QC Criteria: December 8, 2013
• First Posted (ESTIMATE): December 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: AIN457, ankylosing spondylitis, chronic inflammatory disease, inflammatory back pain, secukinumab, self-injection
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457F2314; 2013-001090-24 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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: Yes
• Studies a U.S. FDA-regulated device product: No