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

NCT ID: NCT02771210

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-30
• Study Completion Date: 2019-12-11

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)

Conditions

Psoriatic Arthritis; Axial Spondyloarthritis; Enthesitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Secukinumab

Intervention Type: BIOLOGICAL

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

AIN457/Secukinumab Placebo

Secukinumab Placebo s.c.

Group Type: PLACEBO_COMPARATOR

Secukinumab Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

Other Intervention Names

AIN457A; AIN457/Secukinumab Placebo

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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, , Bulgaria

Novartis Investigative Site

Prague, Czech Republic, Czechia

Novartis Investigative Site

Brno, , Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Uherské Hradiště, , Czechia

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Cologne, , 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

Hanover, , Germany

Novartis Investigative Site

Herne, , Germany

Novartis Investigative Site

Magdeburg, , Germany

Novartis Investigative Site

Magdeburg, , Germany

Novartis Investigative Site

Mainz, , Germany

Novartis Investigative Site

Wuppertal, , Germany

Novartis Investigative Site

Heraklion Crete, Greece, Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Thessaloniki, , Greece

Novartis Investigative Site

Bergamo, BG, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Potenza, PZ, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Verona, VR, Italy

Novartis Investigative Site

Bologna, , Italy

Novartis Investigative Site

Piešťany, , Slovakia

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Torrelavega, Cantabria, Spain

Novartis Investigative Site

Mérida, Extremadura, Spain

Novartis Investigative Site

Ourense, Galicia, Spain

Novartis Investigative Site

Santiago de Compostela, Galicia, Spain

Novartis Investigative Site

Cartagena, Murcia, Spain

Novartis Investigative Site

Vigo, Pontevedra, Spain

Novartis Investigative Site

Barakaldo, Vizcaya, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Málaga, , Spain

Novartis Investigative Site

Pontevedra, , Spain

Novartis Investigative Site

Truro, Cornwall, United Kingdom

Novartis Investigative Site

Leytonstone, London, United Kingdom

Novartis Investigative Site

Stoke-on-Trent, Staffordshire, United Kingdom

Novartis Investigative Site

Barnsley, , United Kingdom

Novartis Investigative Site

Cheshire, , United Kingdom

Novartis Investigative Site

Hull, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Tyne and Wear, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 35578245 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34730795 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33220702 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000972-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAIN457F3301

Identifier Type: -

Identifier Source: org_study_id