Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis

NCT02763046 | Completed Phase 4 Results

• 2 other identifiers: CAIN457FDE032015-004575-74
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 39

Brief Summary

This study assessed the clinical Assessment of SpondyloArthritis international Society (ASAS) 20 response to secukinumab and evaluated to which extent concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced in patients treated with secukinumab or placebo following an initial run-in phase of stable NSAID therapy.

Conditions

Ankylosing Spondylitis

Keywords

Ankylosing Spondylitis; NSAID; ASAS; ASAS-NSAID score; Secukinumab

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12

  ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.

  Baseline, Week 12

Secondary Outcomes (5)

• Proportion of Patients Who Achieved ASAS20 Response in Each Secukinumab Group (Delayed NSAID Tapering and Early NSAID Tapering) Compared With the Placebo Group

  Baseline, Week 12, Week 16

• Mean Change From Baseline in ASAS-NSAID Score at Week 12

  Baseline, Week 12

• Mean Change From Baseline in ASAS-NSAID Score in Each Secukinumab Group After 12 Weeks of Exposure (at Week 12 in the Secukinumab-delayed NSAID Tapering Group and at Week 16 in the Secukinumab-early NSAID Tapering Group)

  Baseline, Week 12 (delayed NSAID tapering), Week 16 (early NSAID tapering)

• Mean Change From Baseline in the BASDAI Total Score

  Baseline, Week 12, Week 16

• Mean Change From Baseline in Health-related Quality of Life as Measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score

  Baseline, Week 12

Study Arms (3)

Secukinumab - delayed NSAID tapering

EXPERIMENTAL

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

Drug: Secukinumab (AIN457) 150 mg s.c.

Secukinumab - early NSAID tapering

EXPERIMENTAL

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

Drug: Secukinumab (AIN457) 150 mg s.c.

Placebo

PLACEBO COMPARATOR

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

Drug: Placebo - Secukinumab (AIN457) 150 mg s.c.

Interventions

Secukinumab (AIN457) 150 mg s.c. DRUG

Induction: 5 x 150 mg secukinumab s.c. weekly Maintenance: 4 x 150 mg secukinumab s.c. every 4 weeks Delayed NSAID tapering (tapering following 4 weeks of secukinumab treatment).

Secukinumab - delayed NSAID tapering

Placebo - Secukinumab (AIN457) 150 mg s.c. DRUG

Placebo for 15 weeks. From Week 16 on, 5 x 150 mg secukinumab s.c. weekly.

Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis of active AS with prior documented radiologic evidence fulfilling the Modified New York criteria for AS
• Active AS assessed by total BASDAI ≥ 4 (0-10) at baseline
• Spinal pain as measured by BASDAI Question 2 ≥ 4 cm on a 0-10 cm numeric rating scale at baseline
• Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline
• Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks prior to randomization, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications
• Patients must report regular intake of NSAIDs of at least 50% of the highest recommended dose at Screening.
• Patients with prior TNFα inhibitor therapy must report regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline after the appropriate washout
• Patients are required to be on a stable dose of NSAIDs for at least 2 weeks before randomization
• Patients who have previously been on a TNFα inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization
• Patients who have been on a TNFα inhibitor (not more than two) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent.
• Patients taking MTX or sulfasalazine are allowed to continue their medication and must have taken it for at least 3 months and be on a stable dose for at least 4 weeks prior to randomization

You may not qualify if:

• Chest X-ray or MRI with evidence of ongoing infectious or malignant process.
• Previous exposure to Secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
• Patients previously treated with any biological immunomodulating agents, except those targeting TNFα
• Patients who have taken more than two anti-TNFα agents
• Pregnant or nursing (lactating) women.
• History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.
• Patients who are intolerant to NSAIDs

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (39)

Novartis Investigative Site

Bad Doberan, 18209, Germany

Location

Novartis Investigative Site

Bayreuth, 95444, Germany

Location

Novartis Investigative Site

Berlin, 12161, Germany

Location

Novartis Investigative Site

Berlin, 12163, Germany

Location

Novartis Investigative Site

Berlin, 13055, Germany

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Berlin, 14059, Germany

Location

Novartis Investigative Site

Chemnitz, 09130, Germany

Location

Novartis Investigative Site

Cologne, 51149, Germany

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Novartis Investigative Site

Cottbus, 03042, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Elmshorn, 25335, Germany

Location

Novartis Investigative Site

Erlangen, 91056, Germany

Location

Novartis Investigative Site

Frankfurt am Main, 60528, Germany

Location

Novartis Investigative Site

Freiberg, 09599, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Hamburg, 22081, Germany

Location

Novartis Investigative Site

Hamburg, 22143, Germany

Location

Novartis Investigative Site

Hamburg, 22415, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Herne, 44649, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Leipzig, 04109, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Magdeburg, 39104, Germany

Location

Novartis Investigative Site

Magdeburg, 39110, Germany

Location

Novartis Investigative Site

München, 80331, Germany

Location

Novartis Investigative Site

München, 81541, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Nienburg, 31582, Germany

Location

Novartis Investigative Site

Nuremberg, 90443, Germany

Location

Novartis Investigative Site

Püttlingen, 66346, Germany

Location

Novartis Investigative Site

Rendsburg, 24768, Germany

Location

Novartis Investigative Site

Saarbrücken, 66111, Germany

Location

Novartis Investigative Site

Schwerin, 19055, Germany

Location

Novartis Investigative Site

Sendenhorst, 48324, Germany

Location

Novartis Investigative Site

Trier, 54292, Germany

Location

Related Publications (1)

• Kiltz U, Baraliakos X, Brandt-Jurgens J, Wagner U, Lieb S, Sieder C, Mann C, Braun J. Efficacy and NSAID-sparing effect of secukinumab 150 mg in ankylosing spondylitis: results from phase IV ASTRUM study. Ther Adv Musculoskelet Dis. 2024 Jun 5;16:1759720X241255486. doi: 10.1177/1759720X241255486. eCollection 2024.

  PMID: 38846755 DERIVED

Related Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

secukinumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 5, 2016
• Study Start: May 31, 2016
• Primary Completion: September 24, 2019
• Study Completion: September 24, 2019
• Last Updated: October 8, 2021
• Results First Posted: October 9, 2020

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (39)