16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Psoriatic Arthritis (FUTURE 4)

A Phase III, Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab (150 mg) in Pre-filled Syringe, With or Without Loading Regimen, to Demonstrate Efficacy, Safety and Tolerability up to 2 Years in Patients With Active Psoriatic Arthritis (FUTURE 4)

The purpose of this study was 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 PsA despite current or previous NSAID or DMARD therapy

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 341
• 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
• Belgium
  • Aalst, Belgium, 9300
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Yvoir, Belgium, 5530
    • Novartis Investigative Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3M9
      • Novartis Investigative Site
  • 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
    • Bruntal, Czech Republic, Czechia, 792 01
      • Novartis Investigative Site
    • Hlucin, Czech Republic, Czechia, 748 01
      • Novartis Investigative Site
    • Praha 2, Czech Republic, Czechia, 128 50
      • Novartis Investigative Site
    • Praha 4, Czech Republic, Czechia, 140 00
      • Novartis Investigative Site
    • Uherske Hradiste, Czech Republic, Czechia, 686 01
      • Novartis Investigative Site
• France
  • Le Mans, France, 72037
    • Novartis Investigative Site
  • Montpellier, France, 34195
    • Novartis Investigative Site
• Germany
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt am Main, Germany, 60528
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Hamburg, Germany, 20095
    • Novartis Investigative Site
  • Hamburg, Germany, 22415
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Nienburg, Germany, 31582
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-461
    • Novartis Investigative Site
  • Dopiewo, Poland, 62 069
    • Novartis Investigative Site
  • Elblag, Poland, 82-300
    • Novartis Investigative Site
  • Lodz, Poland, 90-265
    • Novartis Investigative Site
  • Poznan, Poland, 60-218
    • Novartis Investigative Site
  • Poznan, Poland, 61 113
    • Novartis Investigative Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620028
    • Novartis Investigative Site
  • Ekaterinburg, Russian Federation, 620035
    • Novartis Investigative Site
  • Petrozavodsk, Russian Federation, 185019
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 190068
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150003
    • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, SE-17176
    • Novartis Investigative Site
• United Kingdom
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Novartis Investigative Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Novartis Investigative Site
  • California
    • Upland, California, United States, 91786
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Novartis Investigative Site
  • Florida
    • Palm Harbor, Florida, United States, 34684
      • Novartis Investigative Site
    • Sarasota, Florida, United States, 34239
      • Novartis Investigative Site
  • Illinois
    • Peoria, Illinois, United States, 61602
      • Novartis Investigative Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Novartis Investigative Site
  • Michigan
    • Saint Clair Shores, Michigan, United States, 48081
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • 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
    • Greenville, South Carolina, United States, 29601
      • Novartis Investigative Site
  • Texas
    • Mesquite, Texas, United States, 75150
      • Novartis Investigative Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98122
      • 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.
• Other protocol-defined inclusion criteria do apply.

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 150 mg; 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. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator	Biological: Secukinumab; Secukinumab 150 mg (1 mL liquid formulation) in pre-filled syringes were supplied by Novartis. Each secukinumab 300 mg dose was given as two sc injections of secukinumab 150 mg.
Experimental: Secukinumab 150 mg No load; 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. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator	Biological: Secukinumab; Secukinumab 150 mg (1 mL liquid formulation) in pre-filled syringes were supplied by Novartis. Each secukinumab 300 mg dose was given as two sc injections of secukinumab 150 mg.
Placebo Comparator: Placebo; Placebo to Secukinumab at Baseline, Weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4 until Week 16/24, depending on patients responder status. From Week 16/24, patients were switched to Secukinumab 150 mg every four weeks. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator	Other: Placebo; Placebo to secukinumab was also available in 1.0 mL liquid formulation in prefilled syringe to match the active drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With American College of Rheumatology 20 (ACR20) Response	The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Disability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16	DAS28-CRP score change from baseline using MMRM up to Week 16. DAS-CRP values range between 2.0 and 10. The higher the score, the higher the disease severity. n: Number of subjects with measures at both baseline and the corresponding post baseline visit.	week 16
Psoriatic Area and Severity Index 75 (PASI75)	PASI is a measure of disease activity based on extent of the disease, severity of erythema, scaling and thickness in different body areas affected by psoriasis. PASI75 is an improvement in the PASI score of at least 75% compared to baseline. PASI75 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. PASI75 response using non-responder imputation and rescue penalty up to Week 16	16 weeks
Short Form Health Survey Physical Component Score (SF-36-PCS)	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.	16 weeks
Number of Participants With American College of Rheumatology 50 (ACR50)	The ACR50 response is defined by at least 50% decrease in the swollen and tender joint count, and at least 50% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]. ACR50 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. This table is the ACR50 response using non-responder imputation and rescue penalty up to Week 16	16 weeks
Number of Participants With American College of Rheumatology 20 (ACR20) Response	The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Diability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo	4 weeks

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.
• Kivitz AJ, Nash P, Tahir H, Everding A, Mann H, Kaszuba A, Pellet P, Widmer A, Pricop L, Abrams K. Efficacy and Safety of Subcutaneous Secukinumab 150 mg with or Without Loading Regimen in Psoriatic Arthritis: Results from the FUTURE 4 Study. Rheumatol Ther. 2019 Sep;6(3):393-407. doi: 10.1007/s40744-019-0163-5. Epub 2019 Jun 21.

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 29, 2015
• Primary Completion (Actual): February 16, 2016
• Study Completion (Actual): December 19, 2017

Study Registration Dates

• First Submitted: November 17, 2014
• First Submitted That Met QC Criteria: November 18, 2014
• First Posted (Estimate): November 19, 2014

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: psoriatic arthritis; AIN457; chronic inflammatory disease; loading regimen; secukinumab; self-injection
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: CAIN457F2336; 2014-003849-10 (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