NCT02696031: PREVENT

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

Completed Phase 3 Results posted Last updated 29 April 2022

What this trial tests

Phase 3 trial testing Secukinumab in Non-radiographic Spondyloarthritis in 555 participants. Completed in 11 March 2021.

Timeline

29 April 2016

Primary endpoint
1 July 2019

11 March 2021

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	555
Start date	29 April 2016
Primary completion	1 July 2019
Estimated completion	11 March 2021
Sites	139 locations across Italy, Japan, Poland, South Korea, Netherlands, Russia, Belgium, Sweden

Drugs / interventions tested

• Secukinumab (secukinumab) — full drug profile →
• Placebo

Conditions studied

• Non-radiographic Spondyloarthritis — all drugs for Non-radiographic Spondyloarthritis →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Non-radiographic Spondyloarthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Secukinumab, Load, Core Phase	68
Secukinumab, No Load, Core Phase	70
Placebo, Core Phase	50

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

Group	Value	95% CI
Secukinumab, Load, Core Phase	58
Secukinumab, No Load, Core Phase	66
Placebo, Core Phase	34

The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response Secondary · Week 16 and 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

week 16

Group	Value	95% CI
Secukinumab, Load, Core Phase	74
Secukinumab, No Load, Core Phase	75
Placebo, Core Phase	52

week 52

Group	Value	95% CI
Secukinumab, Load, Core Phase	62
Secukinumab, No Load, Core Phase	70
Placebo, Core Phase	36

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

Group	Value	95% CI
Secukinumab, Load, Core Phase	105
Secukinumab, No Load, Core Phase	107
Placebo, Core Phase	85

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

Group	Value	95% CI
Secukinumab, Load, Core Phase	74
Secukinumab, No Load, Core Phase	66
Placebo, Core Phase	44

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

Group	Value	95% CI
Secukinumab, Load, Core Phase	40
Secukinumab, No Load, Core Phase	39
Placebo, Core Phase	13

Change in Bath Ankylosing Spondylitis Functional Index (BASFI) Secondary · Baseline and Week 16

The Bath Ankylosing Spondylitis Functional Index (BASFI) is a set of 10 questions designed to determine the degree of functional limitation in those subjects with AS. The ten questions were chosen with a major input from subjects with AS. The first 8 questions consider activities related to functional anatomy. The final 2 questions assess the subjects' ability to cope with everyday life. A 100 mm visual analog scale (VAS) is used to answer the questions. The mean of the ten questions gives the BASFI score - a value between 0 and 10. (0 being no problem and 10 being the worst problem, captured

Group	Value	95% CI
Secukinumab, Load, Core Phase	-1.75	± 0.202
Secukinumab, No Load, Core Phase	-1.64	± 0.204
Placebo, Core Phase	-1.01	± 0.206

The Number and Percentage of Patients to Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Secondary · Week 16 and 52

The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) consists of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to the 5 major symptoms of AS. The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI compared to baseline. A higher score on the VAS signifies higher severity.

week 16

Group	Value	95% CI
Secukinumab, Load, Core Phase	69
Secukinumab, No Load, Core Phase	69
Placebo, Core Phase	39

week 52

Group	Value	95% CI
Secukinumab, Load, Core Phase	57
Secukinumab, No Load, Core Phase	65
Placebo, Core Phase	37

Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Secondary · Baseline and Week 16

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a validated assessment tool using 1 through 10 scales (1 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains (fatigue, spinal pain, joint pain/selling, localized tenderness, morning stiffness duration, morning stiffness severity) pertaining to five major symptoms of Ankylosing Spondylitis (AS). The computed final BASDAI score is a value between 0 and 10 with a higher score indicating worse disease. A higher score on the VAS signifies higher severity.

Group	Value	95% CI
Secukinumab, Load, Core Phase	-2.35	± 0.201
Secukinumab, No Load, Core Phase	-2.43	± 0.203
Placebo, Core Phase	-1.46	± 0.205

Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 16 Secondary · Baseline and Week 16

The Ankylosing Spondylitis Quality of Life scores (ASQoL) is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response resulting in overall scores that range from 0 (least severity) to 18 (highest severity). As such, lower score indicate better quality of life. Items include an assessment of mobility/energy, self-care and mood/emotion. The recall period is "at the m

Group	Value	95% CI
Secukinumab, Load, Core Phase	-3.45	± 0.408
Secukinumab, No Load, Core Phase	-3.62	± 0.414
Placebo, Core Phase	-1.84	± 0.421

Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 52 Secondary · Baseline and Week 52

The Ankylosing Spondylitis Quality of Life scores (ASQoL) is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response resulting in overall scores that range from 0 (least severity) to 18 (highest severity). As such, lower score indicate better quality of life. Items include an assessment of mobility/energy, self-care and mood/emotion. The recall period is "at the m

Group	Value	95% CI
Secukinumab, Load, Core Phase	-7.1	± 4.77
Secukinumab, No Load, Core Phase	-7.6	± 5.38
Placebo, Core Phase	-6.4	± 4.64

The Number and Percentage of Patients Who Achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Inactive Disease Secondary · Week 52

Ankylosing Spondylitis Disease Activity Score (ASDAS) - C-reactive protein (CRP) inactive disease criteria are defined as a value below 1.3. Higher score indicates worse symptoms. The formula is: ASDAS-CRP = 0.121 x total back pain + 0.110 x patient global + 0.073 x peripheral pain/swelling + 0.058 x duration of morning stiffness + 0.579 x ln(hsCRP +1)

Group	Value	95% CI
Secukinumab, Load, Core Phase	29
Secukinumab, No Load, Core Phase	44
Placebo, Core Phase	19

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events are reported from first dose of study treatment until end of study treatment plus 12 wks post-treatment, up to a maximum timeframe of 1520 days (approx. 4.2 years). Safety results summarize long term data for all patients for the entire period of their study participation, which, for the majority of pts, combines the core phase and the extension phase (not all pts participated in the extension). The table is presented by dose group, AIN457 150 mg and AIN457 300 mg and placebo.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Any AIN457 150 mg, in Core Phase and Extension Phase

Serious: 48/543 (9%)

Deaths: 0/543

Any AIN457 300 mg in Extension Phase

Serious: 11/254 (4%)

Deaths: 0/254

Any AIN457, In Core Phase and Extension Phase

Serious: 58/543 (11%)

Deaths: 0/543

Placebo, Core Phase

Serious: 8/186 (4%)

Deaths: 0/186

Serious adverse events (83 terms)

Reaction	System	Any AIN457 150 mg, in Core…	Any AIN457 300 mg in Exten…	Any AIN457, In Core Phase …	Placebo, Core Phase
Crohn's disease	Gastrointestinal disorders	—	—	—	—
Tonsillitis	Infections and infestations	—	—	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Iridocyclitis	Eye disorders	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Meniscus injury	Injury, poisoning and procedural complications	—	—	—	—
Synovitis	Musculoskeletal and connective tissue disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Acute coronary syndrome	Cardiac disorders	—	—	—	—
Aortic valve incompetence	Cardiac disorders	—	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Anal fistula	Gastrointestinal disorders	—	—	—	—
Appendiceal mucocoele	Gastrointestinal disorders	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—
Colitis ulcerative	Gastrointestinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Inguinal hernia	Gastrointestinal disorders	—	—	—	—
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Biliary colic	Hepatobiliary disorders	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—
Drug-induced liver injury	Hepatobiliary disorders	—	—	—	—
Hepatitis acute	Hepatobiliary disorders	—	—	—	—
Anal abscess	Infections and infestations	—	—	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	Any AIN457 150 mg, in Core…	Any AIN457 300 mg in Exten…	Any AIN457, In Core Phase …	Placebo, Core Phase
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—

Most-reported serious reactions: Crohn's disease, Tonsillitis, Arthritis, Iridocyclitis, Gastroenteritis, Meniscus injury, Synovitis, Anaemia.

Data from ClinicalTrials.gov NCT02696031 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo-Controlled Phase III Study.
   Deodhar A, Blanco R, Dokoupilová E, Hall S, et al · · 2021 · cited 123× · PMID 32770640 · DOI 10.1002/art.41477
2. Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT.
   Braun J, Blanco R, Marzo-Ortega H, Gensler LS, et al · · 2021 · cited 34× · PMID 34481517 · DOI 10.1186/s13075-021-02613-9
3. Non-Radiographic Axial Spondyloarthritis (nr-axSpA): Advances in Classification, Imaging and Therapy.
   Robinson PC, Sengupta R, Siebert S. · · 2019 · cited 33× · PMID 30788779 · DOI 10.1007/s40744-019-0146-6
4. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications.
   Merola JF, McInnes IB, Deodhar AA, Dey AK, et al · · 2022 · cited 30× · PMID 35305260 · DOI 10.1007/s40744-022-00434-z
5. Secukinumab for ankylosing spondylitis and psoriatic arthritis.
   Lubrano E, Perrotta FM. · · 2016 · cited 29× · PMID 27799780 · DOI 10.2147/tcrm.s100091
6. Clinical Trials Supporting the Role of the IL-17/IL-23 Axis in Axial Spondyloarthritis.
   Ceribelli A, Motta F, Vecellio M, Isailovic N, et al · · 2021 · cited 24× · PMID 34149686 · DOI 10.3389/fimmu.2021.622770
7. Treatment of Axial Spondyloarthritis: What Does the Future Hold?
   Poddubnyy D, Sieper J. · · 2020 · cited 24× · PMID 32691259 · DOI 10.1007/s11926-020-00924-5
8. Tumor necrosis factor-α (TNFα) inhibitors in the treatment of nonradiographic axial spondyloarthritis: current evidence and place in therapy.
   Rios Rodriguez V, Poddubnyy D. · · 2017 · cited 20× · PMID 28835779 · DOI 10.1177/1759720x17706454