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

NCT02696031 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CAIN457H2315
• Study Type: interventional
• Target: 555
• Locations: 23 countries
• Sites: 137

Brief Summary

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

Conditions

Non-radiographic Spondyloarthritis

Keywords

non-radiographic spondyloarthritis; axial spondyloarthritis; Ankylosing Spondylitis

Outcome Measures

Primary Outcomes (2)

• The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 Response at Week 16

  Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain. A higher score on the VAS signifies higher severity.

  Week 16

• The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 52

  Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain. A higher score on the VAS signifies higher severity.

  Week 52

Secondary Outcomes (14)

• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response

  Week 16 and week 52

• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 Response

  Week 16

• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 Response

  Week 16

• The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)

  Week 16

• Change in Bath Ankylosing Spondylitis Functional Index (BASFI)

  Baseline and Week 16

Study Arms (6)

Secukinumab, 150 mg Load (Core phase)

EXPERIMENTAL

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

Drug: Secukinumab

Secukinumab, 150 mg No Load (Core phase)

EXPERIMENTAL

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

Drug: Secukinumab

Placebo (Core phase)

PLACEBO COMPARATOR

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

Drug: Placebo

Core Phase Responder 150 mg (Extension phase)

EXPERIMENTAL

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

Drug: Secukinumab; Drug: Placebo

Core Phase Responder 300 mg (Extension phase)

EXPERIMENTAL

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

Drug: Secukinumab

Core Phase Non-Responder 300 mg (Extension phase)

EXPERIMENTAL

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

Drug: Secukinumab

Interventions

Secukinumab DRUG

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

Also known as: AIN457

Core Phase Non-Responder 300 mg (Extension phase); Core Phase Responder 150 mg (Extension phase); Core Phase Responder 300 mg (Extension phase); Secukinumab, 150 mg Load (Core phase); Secukinumab, 150 mg No Load (Core phase)

Placebo DRUG

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

Also known as: AIN457

Core Phase Responder 150 mg (Extension phase); Placebo (Core phase)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (139)

Novartis Investigative Site

Birmingham, Alabama, 35205, United States

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Beverly Hills, California, 90211, United States

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Fullerton, California, 92835, United States

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Denver, Colorado, 80230, United States

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Gainesville, Florida, 32608, United States

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Idaho Falls, Idaho, 83404, United States

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Bowling Green, Kentucky, 42101, United States

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Lansing, Michigan, 48910, United States

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Great Falls, Montana, 59405, United States

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Albany, New York, 12206, United States

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Potsdam, New York, 13676, United States

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Charlotte, North Carolina, 28204, United States

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Oklahoma City, Oklahoma, 73102, United States

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Portland, Oregon, 97239, United States

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Duncansville, Pennsylvania, 16635, United States

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Charleston, South Carolina, 29460, United States

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Leander, Texas, 78641, United States

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Mesquite, Texas, 75150, United States

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Coffs Harbour, New South Wales, 2450, Australia

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Maroochydore, Queensland, 4558, Australia

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Hobart, Tasmania, 7000, Australia

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Malvern East, Victoria, 3145, Australia

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Woolloongabba, QLD 4102, Australia

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Graz, 8036, Austria

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Vienna, A-1060, Austria

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Brussels, 1200, Belgium

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Genk, 3600, Belgium

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Ghent, 9000, Belgium

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Pleven, 5800, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1784, Bulgaria

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Novartis Investigative Site

Prague, Czech Republic, 128 50, Czechia

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Prague, Czech Republic, 148 00, Czechia

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Prague, Czech Republic, 150 06, Czechia

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Novartis Investigative Site

Brno-Zidonice, CZE, 61500, Czechia

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Brno, CZ, 625 00, Czechia

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Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

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Limoges, Haute Vienne, 87000, France

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Bordeaux, 33076, France

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Boulogne-Billancourt, 92104, France

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Chambray-lès-Tours, 37170, France

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Monaco, 98000, France

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Paris, 75679, France

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Poitiers, 86021, France

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Rouen, 76031, France

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Hanover, Lower Saxony, 30159, Germany

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Berlin, 13125, Germany

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Berlin, 13353, Germany

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Cottbus, 03042, Germany

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Dresden, 01307, Germany

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Erlangen, 91054, Germany

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Freiburg im Breisgau, 79106, Germany

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Hamburg, 22143, Germany

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Hamburg, 22415, Germany

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Hamburg, 22767, Germany

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Herne, 44649, Germany

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Magdeburg, 39110, Germany

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Potsdam, 14469, Germany

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Budapest, 1027, Hungary

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Debrecen, 4032, Hungary

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Eger, 3300, Hungary

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Szeged, 6720, Hungary

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Székesfehérvár, 8000, Hungary

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Veszprém, 8200, Hungary

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Haifa, 3109601, Israel

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Kfar Saba, 4428164, Israel

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Ramat Gan, 52621, Israel

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Tel Aviv, 6423906, Israel

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Verona, VR, 37126, Italy

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Bologna, 40138, Italy

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Novara, 28100, Italy

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Padua, 35128, Italy

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Pisa, 56126, Italy

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Kita-gun, Kagawa-ken, 761-0793, Japan

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Kawachi-Nagano, Osaka, 586-8521, Japan

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Bunkyo Ku, Tokyo, 113-8431, Japan

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Chuo Ku, Tokyo, 104-8560, Japan

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Meguro City, Tokyo, 153-8515, Japan

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Shinjuku Ku, Tokyo, 162 8666, Japan

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Torreón, Coahuila, 27000, Mexico

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Guadalajara, Jalisco, 44160, Mexico

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Culiacan, State of Mexico, 80000, Mexico

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Metepec, State of Mexico, 52140, Mexico

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Amsterdam, 1105 AZ, Netherlands

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Groningen, 9713 GZ, Netherlands

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Maastricht, 6229 HX, Netherlands

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Kongsvinger, 2212, Norway

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Moss, 1538, Norway

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Krakow, 30-510, Poland

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Poznan, 60-218, Poland

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Poznan, 61 113, Poland

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Warsaw, 02 118, Poland

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Warsaw, 04 305, Poland

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Wroclaw, 53-224, Poland

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Almada, 2801 951, Portugal

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Braga, 4710243, Portugal

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Lisbon, 1050-034, Portugal

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Lisbon, 1649-035, Portugal

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Ponte de Lima, 4990 041, Portugal

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Barnaul, 656024, Russia

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Kemerovo, 650000, Russia

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Moscow, 115522, Russia

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Moscow, 127473, Russia

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Saint Petersburg, 197022, Russia

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Saratov, 410053, Russia

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Smolensk, 214019, Russia

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Yekaterinburg, 620028, Russia

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Seoul, 03080, South Korea

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Seoul, 06351, South Korea

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Elda, Alicante, 03600, Spain

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Córdoba, Andalusia, 14004, Spain

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41009, Spain

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Sabadell, Barcelona, 08208, Spain

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Bilbao, Basque Country, 48013, Spain

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Santander, Cantabria, 39008, Spain

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A Coruña, Galicia, 15006, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Vigo, Pontevedra, 36200, Spain

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Valencia, Valencia, 46026, Spain

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Madrid, 28009, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Gothenburg, SE-413 45, Sweden

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Novartis Investigative Site

Lund, 221 85, Sweden

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Uppsala, 751 85, Sweden

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Basel, 4031, Switzerland

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Fribourg, 1708, Switzerland

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Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

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Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

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Leytonstone, London, E11 1NR, United Kingdom

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Stoke-on-Trent, Staffordshire, ST6 7AG, United Kingdom

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Worthing, West Sussex, BN11 2DH, United Kingdom

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Bath, BA1 3NG, United Kingdom

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Doncaster, DN2 5LT, United Kingdom

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Middlesbrough, TS4 3BW, United Kingdom

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Northampton, NN1 5BD, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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Related Publications (5)

• 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 Oct 1;64(10):5446-5454. doi: 10.1093/rheumatology/keaf323.

  PMID: 40489668 DERIVED

• 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.

  PMID: 37194094 DERIVED

• 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.

  PMID: 35305260 DERIVED

• 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.

  PMID: 34481517 DERIVED

• 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.

  PMID: 32770640 DERIVED

MeSH Terms

Conditions

Axial Spondyloarthritis; Spondylitis, Ankylosing

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharma AG

novartis.email@novartis.com

1-888-669-6682

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: March 2, 2016
• Study Start: April 29, 2016
• Primary Completion: July 1, 2019
• Study Completion: March 11, 2021
• Last Updated: April 29, 2022
• Results First Posted: August 7, 2020

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (6); NO (2); SE (3); BU (3); IT (5); KR (2); HU (6); NL (3); ME (4); DE (13); AU (5); BE (3); CZ (6); RU (8); ES (15); CH (2); FR (8); IL (4); PT (5); PL (6); TU (1); GB (9); US (18)