Study of Efficacy and Safety of Secukinumab in Patients With Non-radiographic Axial Spondyloarthritis

NCT ID: NCT02696031

Last Updated: 2022-04-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

555 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-29

Study Completion Date

2021-03-11

Brief Summary

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The purpose of this study was to demonstrate the clinical efficacy, safety and tolerability of secukinumab compared to placebo in patients with nr-axSpA at Week 16 as well as Week 52 and long term efficacy and safety up to Week 104 (core phase) followed by an optional extension phase consisting of a 16-week randomized dose escalation treatment period and a continuous treatment period for up to Week 208

Detailed Description

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Patients were randomized to one of three treatment groups (1:1:1) in the core phase:

* Secukinumab 150 mg Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4
* Secukinumab 150 mg No Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4
* Placebo: placebo (1 mL) s.c. PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4.

All patients received secukinumab 150 mg as open-label treatment from Week 52 up to Week 100, unless they had discontinued study treatment.

At Week 104, all patients who finished the core phase according to the protocol were asked to continue in an optional, exploratory extension phase. Patients who achieved ASAS20 response at Week 104 (Core Phase Responders) were randomized to the following treatment groups (blinded) in the extension phase:

* Core Phase Responder 150 mg: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS and placebo (1 mL) s.c. PFS every four weeks;
* Core Phase Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks.

Core Phase Non-Responders (not achieving ASAS20 at Week 104) were escalated to secukinumab 300 mg in an open-label manner.

\- Core Phase Non-Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks open-label.

Starting from Week 156 onward, a patient could switch to secukinumab 300 mg open-label based on the clinical judgment of disease activity by the investigator.

Conditions

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Non-radiographic Spondyloarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This was a randomized, double-blind, placebo-controlled study. Approximately 555 patients were randomized to one of three treatment groups (secukinumab 150 mg Load, secukinumab 150 mg No Load or placebo in a ratio of 1:1:1):

* Group 1 (secukinumab 150 mg Load): secukinumab 150 mg (1 mL, 150 mg/mL) s.c. prefilled syringe (PFS) at baseline (BSL), Weeks 1, 2 and 3, followed by administration every four weeks starting at Week 4
* Group 2 (secukinumab 150 mg No Load): secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at BSL, placebo at Weeks 1, 2 and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4
* Group 3 (placebo): placebo (1 mL) s.c. PFS at BSL, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4 Based on the clinical judgment of disease activity by the investigator and the patient, background medications, such as NSAIDs and DMARDs, may have been modified or added to treat signs and symptoms of nr-axSpA from Week 16 on.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Secukinumab, 150 mg Load (Core phase)

Secukinumab 150 mg s.c., pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4, Load, Core phase

Group Type EXPERIMENTAL

Secukinumab

Intervention Type DRUG

Induction: 4x 150 mg Secukinumab s.c. weekly Maintenance: 150 mg Secukinumab s.c. monthly

Secukinumab, 150 mg No Load (Core phase)

Secukinumab 150 mg s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4, No Load, Core phase

Group Type EXPERIMENTAL

Secukinumab

Intervention Type DRUG

Induction: 4x 150 mg Secukinumab s.c. weekly Maintenance: 150 mg Secukinumab s.c. monthly

Placebo (Core phase)

Placebo s.c., PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4, Core phase

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Induction: 4x placebo s.c. weekly Maintenance: placebo s.c. monthly

Core Phase Responder 150 mg (Extension phase)

Core Phase Responder 150 mg blinded: secukinumab 150 mg s.c. PFS and placebo (1 mL) s.c. PFS every four weeks, in the Extension phase

Group Type EXPERIMENTAL

Secukinumab

Intervention Type DRUG

Induction: 4x 150 mg Secukinumab s.c. weekly Maintenance: 150 mg Secukinumab s.c. monthly

Placebo

Intervention Type DRUG

Induction: 4x placebo s.c. weekly Maintenance: placebo s.c. monthly

Core Phase Responder 300 mg (Extension phase)

Core Phase Responder 300 mg blinded: 2 injections with secukinumab 150 mg s.c. PFS every four weeks, in the Extension phase

Group Type EXPERIMENTAL

Secukinumab

Intervention Type DRUG

Induction: 4x 150 mg Secukinumab s.c. weekly Maintenance: 150 mg Secukinumab s.c. monthly

Core Phase Non-Responder 300 mg (Extension phase)

Core Phase Non-Responder 300 mg: 2 injections with secukinumab 150 mg s.c. PFS every four weeks open-label, in the Extension phase

Group Type EXPERIMENTAL

Secukinumab

Intervention Type DRUG

Induction: 4x 150 mg Secukinumab s.c. weekly Maintenance: 150 mg Secukinumab s.c. monthly

Interventions

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Secukinumab

Induction: 4x 150 mg Secukinumab s.c. weekly Maintenance: 150 mg Secukinumab s.c. monthly

Intervention Type DRUG

Placebo

Induction: 4x placebo s.c. weekly Maintenance: placebo s.c. monthly

Intervention Type DRUG

Other Intervention Names

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AIN457 AIN457

Eligibility Criteria

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Inclusion Criteria

* Male or non-pregnant, non-nursing female patients at least 18 years of age
* Diagnosis of axial spondyloarthritis according to Ankylosing SpondyloArthritis International Society (ASAS) axial spondyloarthritis criteria
* objective signs of inflammation (magnetic resonance imaging (MRI) or abnormal C-reactive protein)
* active axial spondyloarthritis as assessed by total Bath Ankylosing Spondylitis Disease Activity Index \>=4 cm
* Spinal pain as measured by Bath Ankylosing Spondylitis Disease Activity Index question #2 ≥ 4 cm (0-10 cm) at baseline
* Total back pain as measured by Visual Analogue scale ≥ 40 mm (0-100 mm) at baseline
* Patients should have been on at least 2 different non-steroidal anti-inflammatory drugs with an inadequate response
* Patients who have been on a Tumor Necrosis Factor (TNF) α inhibitor (not more than one) must have experienced an inadequate response

Exclusion Criteria

* Patients with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally
* Inability or unwillingness to undergo MRI
* Chest X-ray or MRI with evidence of ongoing infectious or malignant process
* Patients taking high potency opioid analgesics
* Previous exposure to secukinumab or any other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor
* Pregnant or nursing (lactating) women
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Novartis Investigative Site

Birmingham, Alabama, United States

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Beverly Hills, California, United States

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Fullerton, California, United States

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Denver, Colorado, United States

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Gainesville, Florida, United States

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Idaho Falls, Idaho, United States

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Bowling Green, Kentucky, United States

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Lansing, Michigan, United States

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Great Falls, Montana, United States

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Albany, New York, United States

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Potsdam, New York, United States

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Charlotte, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Duncansville, Pennsylvania, United States

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Charleston, South Carolina, United States

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Leander, Texas, United States

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Mesquite, Texas, United States

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Coffs Harbour, New South Wales, Australia

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Maroochydore, Queensland, Australia

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Hobart, Tasmania, Australia

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Malvern East, Victoria, Australia

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Woolloongabba, , Australia

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Graz, , Austria

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Vienna, , Austria

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Brussels, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Pleven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Prague, Czech Republic, Czechia

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Prague, Czech Republic, Czechia

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Prague, Czech Republic, Czechia

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Brno-Zidonice, CZE, Czechia

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Brno, CZ, Czechia

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Uherské Hradiště, , Czechia

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Limoges, Haute Vienne, France

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Bordeaux, , France

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Boulogne-Billancourt, , France

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Chambray-lès-Tours, , France

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Monaco, , France

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Paris, , France

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Poitiers, , France

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Rouen, , France

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Hanover, Lower Saxony, Germany

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Berlin, , Germany

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Berlin, , Germany

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Cottbus, , Germany

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Dresden, , Germany

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Erlangen, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Herne, , Germany

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Magdeburg, , Germany

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Potsdam, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Eger, , Hungary

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Szeged, , Hungary

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Székesfehérvár, , Hungary

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Veszprém, , Hungary

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Haifa, , Israel

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Kfar Saba, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Verona, VR, Italy

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Bologna, , Italy

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Novara, , Italy

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Padua, , Italy

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Pisa, , Italy

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Kita-gun, Kagawa-ken, Japan

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Kawachi-Nagano, Osaka, Japan

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Bunkyo Ku, Tokyo, Japan

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Chuo Ku, Tokyo, Japan

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Meguro City, Tokyo, Japan

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Shinjuku Ku, Tokyo, Japan

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Torreón, Coahuila, Mexico

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Guadalajara, Jalisco, Mexico

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Culiacan, State of Mexico, Mexico

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Metepec, State of Mexico, Mexico

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Maastricht, , Netherlands

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Kongsvinger, , Norway

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Moss, , Norway

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Krakow, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Almada, , Portugal

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Braga, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Ponte de Lima, , Portugal

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Barnaul, , Russia

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Kemerovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Smolensk, , Russia

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Yekaterinburg, , Russia

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Seoul, , South Korea

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Seoul, , South Korea

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Elda, Alicante, Spain

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Córdoba, Andalusia, Spain

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Málaga, Andalusia, Spain

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Seville, Andalusia, Spain

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L'Hospitalet de Llobregat, Barcelona, Spain

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Sabadell, Barcelona, Spain

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Bilbao, Basque Country, Spain

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Santander, Cantabria, Spain

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A Coruña, Galicia, Spain

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Santiago de Compostela, Galicia, Spain

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Vigo, Pontevedra, Spain

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Valencia, Valencia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Gothenburg, , Sweden

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Lund, , Sweden

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Uppsala, , Sweden

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Basel, , Switzerland

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Fribourg, , Switzerland

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Ankara, , Turkey (Türkiye)

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Westcliff-on-Sea, Essex, United Kingdom

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Leytonstone, London, United Kingdom

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Stoke-on-Trent, Staffordshire, United Kingdom

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Worthing, West Sussex, United Kingdom

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Bath, , United Kingdom

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Doncaster, , United Kingdom

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Middlesbrough, , United Kingdom

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Northampton, , United Kingdom

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Wolverhampton, , United Kingdom

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Countries

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United States Australia Austria Belgium Bulgaria Czechia France Germany Hungary Israel Italy Japan Mexico Netherlands Norway Poland Portugal Russia South Korea Spain Sweden Switzerland Turkey (Türkiye) United Kingdom

References

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Jamaludin A, Windsor R, Ather S, Kadir T, Zisserman A, Braun J, Gensler LS, Ostergaard M, Poddubnyy D, Coroller T, Porter B, Ligozio G, Readie A, Machado PM. Automated detection of spinal bone marrow oedema in axial spondyloarthritis: training and validation using two large phase 3 trial datasets. Rheumatology (Oxford). 2025 Jun 9:keaf323. doi: 10.1093/rheumatology/keaf323. Online ahead of print.

Reference Type DERIVED
PMID: 40489668 (View on PubMed)

Braun J, Blanco R, Marzo-Ortega H, Gensler LS, Van den Bosch F, Hall S, Kameda H, Poddubnyy D, van de Sande M, van der Heijde D, Zhuang T, Stefanska A, Readie A, Richards HB, Deodhar A. Two-year imaging outcomes from a phase 3 randomized trial of secukinumab in patients with non-radiographic axial spondyloarthritis. Arthritis Res Ther. 2023 May 16;25(1):80. doi: 10.1186/s13075-023-03051-5.

Reference Type DERIVED
PMID: 37194094 (View on PubMed)

Merola JF, McInnes IB, Deodhar AA, Dey AK, Adamstein NH, Quebe-Fehling E, Aassi M, Peine M, Mehta NN. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications. Rheumatol Ther. 2022 Jun;9(3):935-955. doi: 10.1007/s40744-022-00434-z. Epub 2022 Mar 19.

Reference Type DERIVED
PMID: 35305260 (View on PubMed)

Braun J, Blanco R, Marzo-Ortega H, Gensler LS, van den Bosch F, Hall S, Kameda H, Poddubnyy D, van de Sande M, Wiksten AS, Porter BO, Shete A, Richards HB, Haemmerle S, Deodhar A. Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT. Arthritis Res Ther. 2021 Sep 4;23(1):231. doi: 10.1186/s13075-021-02613-9.

Reference Type DERIVED
PMID: 34481517 (View on PubMed)

Deodhar A, Blanco R, Dokoupilova E, Hall S, Kameda H, Kivitz AJ, Poddubnyy D, van de Sande M, Wiksten AS, Porter BO, Richards HB, Haemmerle S, Braun J. Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo-Controlled Phase III Study. Arthritis Rheumatol. 2021 Jan;73(1):110-120. doi: 10.1002/art.41477. Epub 2020 Nov 24.

Reference Type DERIVED
PMID: 32770640 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CAIN457H2315

Identifier Type: -

Identifier Source: org_study_id

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