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

Psoriatic Arthritis Clinical Trial

— ACHILLES  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02771210
• Other study ID #: CAIN457F3301
• Secondary ID: 2016-000972-91
• Status: Completed
• Phase: Phase 3
• Start date: August 30, 2016
• Est. completion date: December 11, 2019

Study information

• Verified date: April 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: December 11, 2019
• Est. primary completion date: December 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 TNFa 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Axial Spondyloarthritis
• Enthesitis
• Enthesopathy
• Psoriatic Arthritis
• Spondylarthritis

Intervention

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

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

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Stara Zagora
Bulgaria	Novartis Investigative Site	Targovishte
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Prague 2
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
Czechia	Novartis Investigative Site	Uherske Hradiste
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Cottbus
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Frankfurt am Main
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Wuppertal
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete
Greece	Novartis Investigative Site	Thessaloniki
Italy	Novartis Investigative Site	Bergamo	BG
Italy	Novartis Investigative Site	Bologna
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Potenza	PZ
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Verona	VR
Slovakia	Novartis Investigative Site	Piestany
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Cartagena	Murcia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Merida	Extremadura
Spain	Novartis Investigative Site	Orense	Galicia
Spain	Novartis Investigative Site	Pontevedra
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Torrelavega	Cantabria
Spain	Novartis Investigative Site	Vigo	Pontevedra
United Kingdom	Novartis Investigative Site	Barnsley
United Kingdom	Novartis Investigative Site	Cheshire
United Kingdom	Novartis Investigative Site	Hull
United Kingdom	Novartis Investigative Site	Leytonstone	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Stoke on Trent	Staffordshire
United Kingdom	Novartis Investigative Site	Truro	Cornwall
United Kingdom	Novartis Investigative Site	Tyne And Wear

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Germany,  Greece,  Italy,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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