16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Ankylosing Spondylitis (MEASURE4)

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

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-TNFα therapy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Novartis Investigative Site
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Novartis Investigative Site
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Novartis Investigative Site
• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Vienna, Austria, 1100
    • Novartis Investigative Site
  • Vienna, Austria, A-1060
    • Novartis Investigative Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novartis Investigative Site
  • Plovdiv, Bulgaria, 4000
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1505
    • Novartis Investigative Site
  • Targovishte, Bulgaria, 7700
    • Novartis Investigative Site
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M1
      • Novartis Investigative Site
  • Quebec
    • Pointe-Claire, Quebec, Canada, H9R 3J1
      • Novartis Investigative Site
    • Trois Rivieres, Quebec, Canada, G8Z 1Y2
      • Novartis Investigative Site
• Czechia
  • Czech Republic
    • Ostrava, Czech Republic, Czechia, 772 00
      • Novartis Investigative Site
    • Praha 11, Czech Republic, Czechia, 148 00
      • Novartis Investigative Site
    • Praha 2, Czech Republic, Czechia, 128 50
      • Novartis Investigative Site
    • Uherske Hradiste, Czech Republic, Czechia, 686 01
      • Novartis Investigative Site
• Denmark
  • Frederiksberg, Denmark, 2000
    • Novartis Investigative Site
  • Odense, Denmark, 5000 C
    • Novartis Investigative Site
• Finland
  • Hyvinkaa, Finland, 05800
    • Novartis Investigative Site
  • Jyvaskyla, Finland, FIN-40620
    • Novartis Investigative Site
• Germany
  • Bad Doberan, Germany, 18209
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 13125
    • Novartis Investigative Site
  • Chemnitz, Germany, 09130
    • Novartis Investigative Site
  • Erlangen, Germany, 91056
    • Novartis Investigative Site
  • Germering, Germany, 82110
    • Novartis Investigative Site
  • Hamburg, Germany, 20095
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Muenchen, Germany, 81541
    • Novartis Investigative Site
  • Wurzburg, Germany, 97080
    • Novartis Investigative Site
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 12462
    • Novartis Investigative Site
  • Athens, Greece, 16673
    • Novartis Investigative Site
  • Patras, Greece, 26504
    • Novartis Investigative Site
• Italy
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37134
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Heerlen, Netherlands, 6419 PC
    • Novartis Investigative Site
  • Leiden, Netherlands, 2333 ZA
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3079 DZ
    • Novartis Investigative Site
• Norway
  • Kongsvinger, Norway, 2212
    • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-351
    • Novartis Investigative Site
  • Elblag, Poland, 82-300
    • Novartis Investigative Site
  • Poznan, Poland, 60-218
    • Novartis Investigative Site
  • Poznan, Poland, 61 113
    • Novartis Investigative Site
  • Poznan, Poland, 60-702
    • Novartis Investigative Site
  • Warszawa, Poland, 04 141
    • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation, 656024
    • Novartis Investigative Site
  • Barnaul, Russian Federation, 656050
    • Novartis Investigative Site
  • Kemerovo, Russian Federation, 650000
    • Novartis Investigative Site
  • S.-Petersburg, Russian Federation, 192242
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197341
    • Novartis Investigative Site
  • St-Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
• Slovakia
  • Partizanske, Slovakia, 95801
    • Novartis Investigative Site
  • Sabinov, Slovakia, 08301
    • Novartis Investigative Site
  • Stara Lubovna, Slovakia, 06401
    • Novartis Investigative Site
  • Topolcany, Slovakia, 95501
    • Novartis Investigative Site
  • SVK
    • Piestany, SVK, Slovakia, 921 12
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• Switzerland
  • Fribourg, Switzerland, 1708
    • Novartis Investigative Site
  • St Gallen, Switzerland, CH 9007
    • Novartis Investigative Site
• United Kingdom
  • Doncaster, United Kingdom, DN2 5LT
    • Novartis Investigative Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Novartis Investigative Site
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Novartis Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207-5710
      • Novartis Investigative Site
  • California
    • Upland, California, United States, 91786
      • Novartis Investigative Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Novartis Investigative Site
  • Illinois
    • Peoria, Illinois, United States, 61602
      • Novartis Investigative Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Novartis Investigative Site
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Novartis Investigative Site
  • Texas
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98101
      • 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.

Other protocol-defined inclusion/exclusion criteria do apply.

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 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.	Biological: Secukinumab; Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio; Other Names: Secukinumab (AIN457) 150 mg s.c.; Biological: Secukinumab; Eligible subjects are randomized to each of the three treatment arms in 1:1:1 ratio; Other Names: Secukinumab (AIN457) 150 mg s.c.
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.	Biological: Secukinumab; Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio; Other Names: Secukinumab (AIN457) 150 mg s.c.; Biological: Secukinumab; Eligible subjects are randomized to each of the three treatment arms in 1:1:1 ratio; Other Names: Secukinumab (AIN457) 150 mg s.c.
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.	Biological: Placebo; Eligible subjects are randomized to each of the three treatment arms in a 1:1:1 ratio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Responded for Assessment of Spondyloarthritis International Society 20 Criteria (ASAS20) at 16 Weeks	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20 percent (%) and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: 1. Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe 2. Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale 4. Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem)	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Responded for ASAS 40 Response at 16 Weeks	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).	16 Weeks
Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) at 16 Weeks	Blood levels of C-reactive protein (CRP) is an acute phase reactant, which are indicative of inflammation and of its severity, and can be used to monitor treatment response. A hsCRP test is implemented to assess the efficacy of secukinumab (with or without load) versus placebo in reducing ankylosing spondylitis elicited systemic inflammation over the time.	Baseline, 16 Weeks
Percentage of Participants Responded for ASAS 5/6 Response at 16 Weeks	ASAS 5/6 response is a validated composite assessment, defined as an improvement of at least 20% in score in at least 5 of 6 clinical domains relevant to ankylosing spondylitis and no worsening in the remaining domain. ASAS domains includes: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem); Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; C-reactive protein (CRP, acute phase reactant).	16 Weeks
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 16 Weeks	BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating "worst problem" on continuous VAS), to answer 6 questions (clinical domains) pertaining to 5 major symptoms of ankylosing spondylitis. Computed composite scores of 4 or greater indicate suboptimal disease control. BASDAI questions includes: Fatigue; Spinal pain; Joint pain / swelling; Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments); Morning stiffness duration; Morning stiffness severity. Each symptom has equal weighting, the mean of two scores related to morning stiffness was taken (questions 5 and 6). The resulting 0 to 10 score was added to the scores from questions 1-4. The resulting 0 to 50 score was divided by 5 to give a final 0-10 BASDAI score. BASDAI was a quick and simple index taking between 30 seconds and 2 minutes for completion.	Baseline, 16 Weeks
Change From Baseline in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)	SF-36 is a 36 item questionnaire which measures Quality of Life across eight subscales that were scored individually: physical functioning, role- physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores are weighted sums of the questions in each section. Scores range from 0-100. Lower scores = more disability, higher scores = less disability. The overall summary scores, SF-36 physical Component Summary (PCS) was used to assess improvement from baseline in the Health-Related Quality Of Life of subjects. The change in SF-36 scores were evaluated using MMRM.	Baseline, 16 Weeks
Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) at 16 Weeks	ASQoL is a self-administered 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 subject with ankylosing spondylitis: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score ranges from 0 (good QoL) to 18 (poor QoL). The change in ASQoL scores was evaluated using a mixed effect repeated measures model (MMRM).	Baseline, 16 Weeks
Number of Participants With Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs) and Related Discontinuations at 104 Weeks	AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.	104 Weeks
Percentage of Participants Responded for ASAS 20 at Week 4	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 20% and 1 unit on a scale of 10 in three main domains and no worsening of at least 20% and 1 unit on a scale of 10 in the fourth domain within a defined time frame. Four main ASAS domains include: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).	Week 4
Percentage of Participants Responded for ASAS 40 Response at Week 4	ASAS 20 response is a validated composite assessment, defined as an improvement of at least 40% and 2 unit on a scale of 10 in three main domains and no worsening at all in the remaining domain within a defined time frame. Four main ASAS domains include: Patient's global assessment of disease activity measured on a 100 mm VAS ranging from not severe to very severe; Patient's assessment of back pain, measured on a 100 mm VAS ranging from no pain to unbearable pain; Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions regarding ability to perform specific tasks as measured by a 0-10 VAS scale; Inflammation represented by average of duration and severity of morning stiffness for last 2 questions on BASDAI scale (0 - no problem, 10 - worst problem).	Week 4

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 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.
• Kivitz AJ, Wagner U, Dokoupilova E, Supronik J, Martin R, Talloczy Z, Richards HB, Porter B. Efficacy and Safety of Secukinumab 150 mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-week Results from MEASURE 4 Study. Rheumatol Ther. 2018 Dec;5(2):447-462. doi: 10.1007/s40744-018-0123-5. Epub 2018 Aug 18.

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): May 18, 2015
• Primary Completion (ACTUAL): February 23, 2016
• Study Completion (ACTUAL): January 2, 2018

Study Registration Dates

• First Submitted: February 28, 2014
• First Submitted That Met QC Criteria: June 6, 2014
• First Posted (ESTIMATE): June 9, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: November 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: CAIN457F2320; 2013-005575-41 (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