Clinical trial NCT02771210: Study of Efficacy and Safety of Secukinumab in Psoriatic Arthritis and Axial Spondyloarthritis Patients With Active Enthesitis Including One Achilles Tendon Site
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Axial Spondyloarthritis
Enthesitis
Keywords: Active psoriatic arthritis
Axial spondyloarthritides
Subcutaneous
Secukinumab in prefilled syringe
Enthesitis
Achilles tendon
AxSpA
PsA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-05-13
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Double-blind
Primary purpose: TREATMENT

Brief 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.

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Number (%) of Patients With Resolution of Achilles Tendon Enthesitis
timeFrame: Week 24
Secondary outcomes:
measure: Mean Change of Heel Pain
timeFrame: Week 24
measure: Number (%) of Patients With Improvement of Bone Marrow Edema
timeFrame: Week 24
measure: Number (%) of Patients With Resolution of Enthesitis as Assessed by LEI
timeFrame: Week 24
measure: Mean Change of Physician's Global Assessment of Disease Activity
timeFrame: Week 24
measure: Mean Change of Patient's Global Assessment of Disease Activity
timeFrame: Week 24
measure: Mean Change of Physician's Assessment of Heel Enthesopathy Activity
timeFrame: Week 24
measure: Mean Change of Patient's Assessment of Heel Enthesopathy Activity
timeFrame: Week 24
measure: Mean Change in Short Form-36 (SF-36) v2
timeFrame: Week 24
measure: Percentage of Patients With Resolution of Achilles Tendon Enthesitis After Switching From Placebo to Secukinumab
timeFrame: Weeks 24 and 52
measure: Mean Change of Heel Pain After Switching From Placebo to Secukinumab
timeFrame: Change from week 24 to week 52
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Stara Zagora
country: Bulgaria
facility: Novartis Investigative Site
city: Targovishte
country: Bulgaria
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Prague 2
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Cottbus
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Bergamo
country: Italy
facility: Novartis Investigative Site
state: BG
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Potenza
country: Italy
facility: Novartis Investigative Site
state: PZ
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Piestany
country: Slovakia
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Torrelavega
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Merida
country: Spain
facility: Novartis Investigative Site
state: Extremadura
city: Orense
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Cartagena
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
state: Vizcaya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
city: Pontevedra
country: Spain
facility: Novartis Investigative Site
city: Truro
country: United Kingdom
facility: Novartis Investigative Site
state: Cornwall
city: Leytonstone
country: United Kingdom
facility: Novartis Investigative Site
state: London
city: Stoke on Trent
country: United Kingdom
facility: Novartis Investigative Site
state: Staffordshire
city: Barnsley
country: United Kingdom
facility: Novartis Investigative Site
city: Cheshire
country: United Kingdom
facility: Novartis Investigative Site
city: Hull
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Tyne And Wear
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.