Study of Efficacy and Safety of Secukinumab in Psoriatic Arthritis and Axial Spondyloarthritis Patients With Active Enthesitis Including One Achilles Tendon Site (ACHILLES)

A Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab to Demonstrate Efficacy in the Treatment of Enthesitis at the Achilles Tendon up to 1 Year in Adult Patients With Active Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA) (ACHILLES)

The purpose of this study was to demonstrate efficacy, including effects on inflammation by magnetic resonance imaging (MRI) assessments, of secukinumab on Achilles tendon enthesitis for up to 1 year with a primary focus at Week 24, in patients with active Psoriatic Arthritis and axial Spondyloarthritis despite current or previous non-steroidal anti-inflammatory drugs (NSAID) and/or disease modifying anti-rheumatic drug (DMARD) and/or anti-TNFα therapy.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis; Enthesitis; Axial Spondyloarthritis
• Intervention / Treatment: Biological: Secukinumab; Drug: Secukinumab Placebo

Detailed Description

Primary endpoint was at week 24 but there was no interim Clinical Study Report. While Protocol states at chapter 9.7 that a week 24 analysis may be provided (not mandatory as per protocol), all data has been analyzed at week 52.

Some of the secondary endpoints include the whole study period up to week 52 (to address questions on switching placebo to active drug)

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1407
    • Novartis Investigative Site
  • Stara Zagora, Bulgaria, 6000
    • Novartis Investigative Site
  • Targovishte, Bulgaria, 7700
    • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 63800
    • Novartis Investigative Site
  • Prague 2, Czechia, 128 50
    • Novartis Investigative Site
  • Uherske Hradiste, Czechia, 686 01
    • Novartis Investigative Site
  • Czech Republic
    • Praha 4, Czech Republic, Czechia, 140 59
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14059
    • Novartis Investigative Site
  • Berlin, Germany, 12435
    • Novartis Investigative Site
  • Cottbus, Germany, 03042
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt am Main, Germany, 60528
    • Novartis Investigative Site
  • Hamburg, Germany, 22415
    • Novartis Investigative Site
  • Hamburg, Germany, 22391
    • Novartis Investigative Site
  • Hannover, Germany, 30161
    • Novartis Investigative Site
  • Herne, Germany, 44649
    • Novartis Investigative Site
  • Koeln, Germany, 50937
    • Novartis Investigative Site
  • Magdeburg, Germany, 39110
    • Novartis Investigative Site
  • Magdeburg, Germany, 39104
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Wuppertal, Germany, 42105
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
  • Athens, Greece, 115 21
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • Thessaloniki, Greece, 54642
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24128
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20100
      • Novartis Investigative Site
  • PZ
    • Potenza, PZ, Italy, 85100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10128
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37134
      • Novartis Investigative Site
• Slovakia
  • Piestany, Slovakia, 92101
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28942
    • Novartis Investigative Site
  • Malaga, Spain, 29009
    • Novartis Investigative Site
  • Pontevedra, Spain, 36001
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Cantabria
    • Torrelavega, Cantabria, Spain, 39300
      • Novartis Investigative Site
  • Extremadura
    • Merida, Extremadura, Spain, 06800
      • Novartis Investigative Site
  • Galicia
    • Orense, Galicia, Spain, 32005
      • Novartis Investigative Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Murcia
    • Cartagena, Murcia, Spain, 30202
      • Novartis Investigative Site
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36200
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
    • Novartis Investigative Site
  • Cheshire, United Kingdom, CW1 4QJ
    • Novartis Investigative Site
  • Hull, United Kingdom, HU3 2JZ
    • Novartis Investigative Site
  • London, United Kingdom, NW3 2QG
    • Novartis Investigative Site
  • Tyne And Wear, United Kingdom, NE29 8NH
    • Novartis Investigative Site
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Novartis Investigative Site
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Novartis Investigative Site
  • Staffordshire
    • Stoke on Trent, Staffordshire, United Kingdom, ST6 7AG
      • 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

Key Inclusion Criteria:

- Patients with Psoriatic arthritis: Diagnosis of Psoriatic arthritis as per the Classification criteria for Psoriatic Arthritis (CASPAR criteria) with symptoms for at least 6 months and active Psoriatic arthritis as assessed by ≥ 1 tender joints out of 78 and ≥ 1 swollen joints out of 76 at Baseline (dactylitis of a digit counts as one joint each).

- Patients with Axial Spondyloarthritis: Diagnosis of Axial Spondyloarthritis as per the classification of the Assessment of Spondyloarthritis International Society axial Spondyloarthritis (ASAS) criteria and objective signs of inflammation at Screening (magnetic resonance imaging (MRI) or definite radiographic sacroilitis and/or abnormal C-Reactive Protein) and active disease assessed by total Bath ankylosing spondylitis disease activity index (BASDAI) ≥ 4 (0-10) at Baseline.

• Diagnosis of Achilles tendon enthesitis according to swelling and tenderness at the insertional site of the Achilles tendon into the calcaneus.
• Onset of heel pain ≥ 1 month at Baseline.
• Heel enthesitis that is magnetic resonance imaging (MRI)-positive according to the investigator's judgement.
• Patients who have been exposed to up to two TNFα inhibitors.

Key Exclusion Criteria:

• Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process.
• Previous exposure to secukinumab or other biologic drug directly targeting Interleukin (IL)-17 or Interleukin (IL)-17 receptor.
• Ongoing use of psoriasis treatments / medications (e.g. topical corticosteroids, ultraviolet (UV) therapy) at randomization.
• Patients who have previously been exposed to more than two Tumor necrosis factor (TNF) inhibitors (investigational or approved).
• Patients who have ever received biologic immunomodulating agents (investigational or approved), except those targeting Tumor necrosis factor (TNF) inhibitors.
• Pregnant or nursing (lactating) women.
• History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AIN457/Secukinumab; Secukinumab 150 mg s.c. or Secukinumab 300 mg s.c., respective dose was assigned according to underlying condition, in case of PsA according to severity of concomitant Psoriasis or pre-exposure to anti-TNFα	Biological: Secukinumab; Induction: Week 0,1,2,3 150 mg or 300 mg Secukinumab s.c. Maintenance: 150 mg or 300 mg Secukinumab s.c. every 4 weeks starting at Week 4; Other Names: AIN457A
Placebo Comparator: AIN457/Secukinumab Placebo; Secukinumab Placebo s.c.	Drug: Secukinumab Placebo; Induction: Week 0,1,2,3 Secukinumab Placebo s.c. Maintenance: Secukinumab Placebo s.c. every 4 weeks starting at Week 4 until Week 24 followed by 150 or 300 mg Secukinumab s.c. every 4 weeks; Other Names: AIN457/Secukinumab Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number (%) of Patients With Resolution of Achilles Tendon Enthesitis	Number (%) of patients with resolution of Achilles tendon enthesitis (affected foot) as assessed by respective subcomponent of Leeds enthesitis index (LEI) at Week 24. The primary analysis was performed via a logistic regression model with the factors treatment, country, and stratification factor diagnosis (PsA or axSpA); patients with a missing assessment were considered as responders if they had already met the response criterion at the time of last assessment.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change of Heel Pain	Mean change of heel pain from baseline to Week 24 measured by Numeric Rating Scale (NRS) ranging from 0 to 10, with 0 representing no pain and 10 representing worst pain (e.g. "pain as bad as you can imagine" or "worst pain imaginable").	Week 24
Number (%) of Patients With Improvement of Bone Marrow Edema	Number (%) of patients with an improvement of bone marrow edema from baseline to Week 24 as assessed by the respective subcomponent of the Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) in the affected foot.	Week 24
Number (%) of Patients With Resolution of Enthesitis as Assessed by LEI	Number (%) of patients with resolution of enthesitis as assessed by the Leeds enthesitis index (LEI) at Week 24.	Week 24
Mean Change of Physician's Global Assessment of Disease Activity	Mean change of physician's global assessment (PhGA) of disease activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe.	Week 24
Mean Change of Patient's Global Assessment of Disease Activity	Mean change of patient's global assessment (PGA) of disease activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe.	Week 24
Mean Change of Physician's Assessment of Heel Enthesopathy Activity	Mean change of physician's assessment of heel enthesopathy activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe.	Week 24
Mean Change of Patient's Assessment of Heel Enthesopathy Activity	Mean change of patient's assessment of heel enthesopathy activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe.	Week 24
Mean Change in Short Form-36 (SF-36) v2	Mean change in Short Form-36 (SF-36) v2 as an indicator of overall health status The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 Lower scores = more disability, higher scores = less disability	Week 24
Percentage of Patients With Resolution of Achilles Tendon Enthesitis After Switching From Placebo to Secukinumab	Percentage of patients with resolution of Achilles tendon enthesitis (affected foot) after switching from placebo to secukinumab at Week 24	Weeks 24 and 52
Mean Change of Heel Pain After Switching From Placebo to Secukinumab	Mean change of heel pain after switching from placebo to secukinumab from Week 24 to week 52 measured by Numeric Rating Scale (NRS) ranging from 0 to 10, with 0 representing no pain and 10 representing worst pain (e.g. "pain as bad as you can imagine" or "worst pain imaginable").	Change from week 24 to week 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Baraliakos X, Sewerin P, de Miguel E, Pournara E, Kleinmond C, Shekhawat A, Jentzsch C, Wiedon A, Behrens F; ACHILLES study group. Magnetic resonance imaging characteristics in patients with spondyloarthritis and clinical diagnosis of heel enthesitis: post hoc analysis from the phase 3 ACHILLES trial. Arthritis Res Ther. 2022 May 16;24(1):111. doi: 10.1186/s13075-022-02797-8.
• Behrens F, Sewerin P, de Miguel E, Patel Y, Batalov A, Dokoupilova E, Kleinmond C, Pournara E, Shekhawat A, Jentzsch C, Wiedon A, Baraliakos X; ACHILLES study group. Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial. Rheumatology (Oxford). 2022 Jul 6;61(7):2856-2866. doi: 10.1093/rheumatology/keab784.
• Baraliakos X, Sewerin P, de Miguel E, Pournara E, Kleinmond C, Wiedon A, Behrens F. Achilles tendon enthesitis evaluated by MRI assessments in patients with axial spondyloarthritis and psoriatic arthritis: a report of the methodology of the ACHILLES trial. BMC Musculoskelet Disord. 2020 Nov 21;21(1):767. doi: 10.1186/s12891-020-03775-4.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2016
• Primary Completion (Actual): December 11, 2019
• Study Completion (Actual): December 11, 2019

Study Registration Dates

• First Submitted: March 31, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Subcutaneous; PsA; Achilles tendon; Active psoriatic arthritis; Axial spondyloarthritides; Secukinumab in prefilled syringe; Enthesitis; AxSpA
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Wounds and Injuries; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Tendinopathy; Psoriasis; Bone Diseases, Infectious; Arthritis; Arthritis, Psoriatic; Enthesopathy; Spondylitis; Spondylarthritis; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CAIN457F3301; 2016-000972-91 (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