24 Week Efficacy and 3-year Safety and Efficacy of Secukinumab in Active Psoriatic Arthritis

A Phase III, Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab in Autoinjectors, to Demonstrate Efficacy at 24 Weeks and to Assess the Long Term Safety, Tolerability and Efficacy up to 3 Years in Subjects With Active Psoriatic Arthritis

The purpose of this study is to provide 24 - 52 week efficacy, safety and tolerability data, and up to 3-year efficacy, safety and tolerability data in subjects with active Psoriatic Arthritis despite current or previous nonsteroidal anti-inflammatory drug (NSAID), disease-modifying antirheumatic drug (DMARD) therapy and/or previous anti-tumor necrosis factor alpha (TNFα) therapy.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Biological: Secukinumab; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 414
• 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
• Bulgaria
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1505
    • Novartis Investigative Site
  • Veliko Tarnovo, Bulgaria, 5000
    • Novartis Investigative Site
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3M9
      • Novartis Investigative Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M9W 4L6
      • Novartis Investigative Site
  • Quebec
    • Trois Rivieres, Quebec, Canada, G8Z 1Y2
      • Novartis Investigative Site
• Czechia
  • Czech Republic
    • Bruntal, Czech Republic, Czechia, 792 01
      • Novartis Investigative Site
    • Praha 2, Czech Republic, Czechia, 128 50
      • Novartis Investigative Site
    • Uherske Hradiste, Czech Republic, Czechia, 686 01
      • Novartis Investigative Site
• Germany
  • Aachen, Germany, 52064
    • Novartis Investigative Site
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Chemnitz, Germany, 09130
    • Novartis Investigative Site
  • Erlangen, Germany, 91056
    • Novartis Investigative Site
  • Gommern, Germany, 39245
    • Novartis Investigative Site
  • Hamburg, Germany, 22081
    • Novartis Investigative Site
  • Hamburg, Germany, 20095
    • Novartis Investigative Site
  • Hamburg, Germany, 22415
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Hildesheim, Germany, 31134
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Zerbst, Germany, 39261
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95100
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10128
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Heerlen, Netherlands, 6419 PC
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3079 DZ
    • Novartis Investigative Site
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Novartis Investigative Site
  • Ponce, Puerto Rico, 00716
    • Novartis Investigative Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454076
    • Novartis Investigative Site
  • Ekaterinburg, Russian Federation, 620028
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115522
    • Novartis Investigative Site
  • Rostov on Don, Russian Federation, 344022
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410053
    • Novartis Investigative Site
  • Sestroretsk, Russian Federation, 197706
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Spain
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
• Switzerland
  • Fribourg, Switzerland, 1708
    • Novartis Investigative Site
  • St Gallen, Switzerland, CH 9007
    • Novartis Investigative Site
• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
    • Novartis Investigative Site
  • Eastbourne, United Kingdom, BN21 2UD
    • Novartis Investigative Site
  • Harrogate, United Kingdom, HG2 7SX
    • Novartis Investigative Site
  • Hull, United Kingdom, HU3 2JZ
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • London, United Kingdom, NW3 2QG
    • Novartis Investigative Site
  • Manchester, United Kingdom, M23 9LT
    • Novartis Investigative Site
  • Torquay, United Kingdom, TQ2 7AA
    • Novartis Investigative Site
  • Tyne And Wear, United Kingdom, NE29 8NH
    • Novartis Investigative Site
  • England
    • London, England, United Kingdom, E11 1NR
      • Novartis Investigative Site
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Novartis Investigative Site
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom, WS11 2XY
      • Novartis Investigative Site
    • Stoke on Trent, Staffordshire, United Kingdom, ST6 7AG
      • Novartis Investigative Site
• United States
  • Florida
    • Aventura, Florida, United States, 33180
      • Novartis Investigative Site
    • Palm Harbor, Florida, United States, 34684
      • Novartis Investigative Site
    • Sarasota, Florida, United States, 34239
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Novartis Investigative Site
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Novartis Investigative Site
  • New York
    • Albany, New York, United States, 12206
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78731
      • Novartis Investigative Site
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site
  • Washington
    • Wenatchee, Washington, United States, 98801
      • 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:

• Diagnosis of Psoriatic Arthritis (PsA) classified by ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria.
• Rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative.
• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis.
• Inadequate control of symptoms with NSAID.

Exclusion Criteria:

• Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process.
• Subjects taking high potency opioid analgesics.
• Previous exposure to secukinumab or other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor.
• Ongoing use of prohibited psoriasis treatments / medications.
• Subjects who have ever received biologic 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 Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab (AIN457) 150 mg s.c.; 1 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.	Biological: Secukinumab; Secukinumab 150 mg provided in a 1 mL autoinjector (1 autoinjector for 150 mg dose, 2 autoinjectors for 300 mg dose); Other Names: Secukinumab 300 mg; Secukinumab 150 mg
Experimental: Secukinumab (AIN457) 300 mg s.c.; 2 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.	Biological: Secukinumab; Secukinumab 150 mg provided in a 1 mL autoinjector (1 autoinjector for 150 mg dose, 2 autoinjectors for 300 mg dose); Other Names: Secukinumab 300 mg; Secukinumab 150 mg
Placebo Comparator: Placebo; Matching Placebo at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4.	Biological: Placebo; Secukinumab placebo provided in 1 mL autoinjector

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Achieving American College of Rheumatology 20 (ACR20) Response Criteria on Secukinumab Versus Placebo at Week 24	A patient will be considered as improved according the ACR20 criteria if she/he has at least 20% decrease in the swollen and tender joint count, and at least 20% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Achieving American College of Rheumatology 50 (ACR50) Response Criteria on Secukinumab Versus Placebo at Week 24	A patient will be considered as improved according the ACR50 criteria if she/he has at least 50% decreases in the swollen and tender joint count, and at least 50% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]	Week 24
Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing hsCRP) in Subjects Treated With Secukinumab Versus Placebo at Week 24	DAS28-CRP is a measure of disease activity based on 28-Swollen and Tender Joint Count [proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2)], CRP, and the Patient's Global Assessment of disease activity. Values range from 2.0 to 10.0 where higher values mean a higher disease activity. DAS28-CRP < 2.6 is interpreted as remission.	Week 24
Proportion of Subjects Achieving a Psoriatic Area and Severity Index 75 (PASI75) Response in Subjects on Secukinumab Versus Placebo at Week 24	PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI75 represents an improvement in the PASI score of at least 75% as compared with baseline.	Week 24
Change From Baseline in Physical Function Component of the Short-form Health Survey (SF-36-PCS) in Subjects Treated With Secukinumab Versus Placebo at Week 24	SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo. The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.	Week 24
Percentage of Subjects Achieving a Psoriatic Area and Severity Index 90 (PASI90) Response in Subjects Treated With Secukinumab Versus Placebo at Week 24	PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI90 represents an improvement in the PASI score of at least 90% as compared with baseline.	Week 24
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI Score) in Subjects Treated With Secukinumab Versus Placebo at Week 24	The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement.	Week 24
Proportion of Patients With Dactylitis at Week 24 in the Subset of Patients Who Had Dactylitis at Baseline	The presence of dactylitis was assessed by dactylitis count (number of fingers and toes with dactylitis, with a range of 0-20). If dactylitis is present with any finger or toe, the patient is counted as a patient with dactylitis.	Week 24
Proportion of Patients With Enthesitis at Week 24 in the Subset of Patients Who Had Enthesitis at Baseline	The presence of Enthesitis was assessed using a validated enthesitis index that uses 6 sites for evaluation of enthesitis: lateral epicondyle humerus L + R, proximal achilles L + R and medial condyle femur. If enthesitis is present at any of the 6 sites, the subject is counted as a subject with enthesitis.	Week 24
Number of Participants With Treatment Emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by Primary System Organ Class (SOC)	Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC).	From first dose of study treatment to last study visit, up to 3 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Pournara E, Kormaksson M, Nash P, Ritchlin CT, Kirkham BW, Ligozio G, Pricop L, Ogdie A, Coates LC, Schett G, McInnes IB. Clinically relevant patient clusters identified by machine learning from the clinical development programme of secukinumab in psoriatic arthritis. RMD Open. 2021 Nov;7(3):e001845. doi: 10.1136/rmdopen-2021-001845.
• 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.
• Coates LC, Wallman JK, McGonagle D, Schett GA, McInnes IB, Mease PJ, Rasouliyan L, Quebe-Fehling E, Asquith DL, Fasth AER, Pricop L, Gaillez C. Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies. Arthritis Res Ther. 2019 Dec 4;21(1):266. doi: 10.1186/s13075-019-2055-z.
• Nash P, Mease PJ, McInnes IB, Rahman P, Ritchlin CT, Blanco R, Dokoupilova E, Andersson M, Kajekar R, Mpofu S, Pricop L; FUTURE 3 study group. Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3). Arthritis Res Ther. 2018 Mar 15;20(1):47. doi: 10.1186/s13075-018-1551-x.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2014
• Primary Completion (Actual): May 27, 2015
• Study Completion (Actual): March 28, 2018

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: November 14, 2013
• First Posted (Estimate): November 21, 2013

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: PsA; Psoriatic arthritis; AIN457; secukinumab; ACR; CASPAR; autoinjector; PASDAS
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457F2318; 2013-004002-25 (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