AScalate: Treat-to-target in Axial Spondyloarthritis

NCT03906136 | Completed Phase 3 Results

• 2 other identifiers: CAIN457HDE012018-003882-32
• Study Type: interventional
• Target: 304
• Locations: 2 countries
• Sites: 47

Brief Summary

This was a randomized, parallel-group, open-label, multicenter study in patients with active axSpA. The aim of the study was to demonstrate that the efficacy of a T2T approach (with secukinumab as a first-line biologic) was superior to a SOC approach in terms of achieving strong clinical efficacy in patients with active axSpA who were naïve to biological therapy and who had an inadequate response to prior non-steroidal anti-inflammatory drug (NSAID) treatment.

Conditions

Axial Spondyloarthritis

Keywords

axial spondyloarthritis; axSpA; treat-to-target; T2T; secukinumab; AIN457; Non-Radiographic Axial Spondyloarthritis; nr-axSpA; Radiographic Axial Spondyloarthritis; r-axSpA

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Achieving an ASAS40 Response at Week 24

  Assessment of SpondyloArthritis International Society criteria (ASAS) consists of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 0 - 10 in at least three of the four ASAS domains and no worsening at all in the remaining domain. A score of 0 indicates less severity; a score of 10 indicates more severity. Percentage was calculated from a logistic regression model: logit(proportion) = treatment + baseline quick C-reactive protein (CRP) + baseline weight.

  Baseline, Week 24

Secondary Outcomes (14)

• Percentage of Patients Achieving an ASAS40 Response at Week 12

  Baseline, Week 12

• Percentage of Patients Achieving ASAS20 Response

  Baseline, Weeks 12 and 24

• Percentage of Patients Achieving ASAS Partial Remission

  Baseline, Weeks 12 and 24

• Percentage of Patients Meeting the Ankylosing Spondylitis Disease Activity Score (ASDAS) Definition of Inactive Disease

  Baseline, Weeks 12 and 24

• Percentage of Patients With ASDAS Major Improvement

  Baseline, Weeks 12 and 24

Study Arms (2)

TREAT-TO-TARGET (T2T)

EXPERIMENTAL

Patients received secukinumab 150 mg subcutaneous (s.c.) weekly until Week 4 (Baseline, Week 1, Week 2, Week 3, Week 4)) and then at Week 8. At Week 12, if ASDAS clinically important improvement was achieved and maintained, patients received treatment up to Week 32 if they maintained the response. If ASDAS clinically important improvement was not achieved, patients received an escalated dose of secukinumab 300 mg s.c. every 4 weeks until Week 20. At Week 24, patients who were receiving secukinumab 300 mg, and achieved ASDAS clinically important improvement, continued treatment up to Week 32. If patients did not achieve ASDAS clinically important improvement, they were switched to adalimumab biosimilar (Hyrimoz®) 40 mg s.c. every 2 weeks until Week 34. Each patient was treated for a maximum of 36 weeks (last dose of secukinumab at Week 32, last dose of adalimumab biosimilar (Hyrimoz®) at Week 34).

Biological: Secukinumab/Adalimumab-Biosimilar

Standard-of-care (SOC)

ACTIVE COMPARATOR

Patients received SOC treatment according to local practice standards by their treating rheumatologist following latest treatment recommendations with NSAIDs as the first-choice drug treatment and disease-modifying anti-rheumatic drugs (DMARDs) for patients with active disease despite the use (or intolerance/contraindication) of NSAIDs.

Other: Standard-of-care

Interventions

Secukinumab/Adalimumab-Biosimilar BIOLOGICAL

Secukinumab 150 mg, s.c. Secukinumab 300 mg, s.c. Adalimumab biosimilar 40 mg, s.c.

TREAT-TO-TARGET (T2T)

Standard-of-care OTHER

Treatment according to local practice standards by the rheumatologist following latest treatment recommendations with NSAIDs as the first-choice drug treatment and DMARDs for patients with active disease despite the use (or intolerance/contraindication) of NSAIDs.

Standard-of-care (SOC)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Axial Spondyloarthritis, axSpA (either Non-Radiographic Axial Spondyloarthritis or Radiographic Axial Spondyloarthritis) fulfilling the Ankylosing Spondyloarthritis International Society classification criteria for axSpA
• Active disease as defined by having an Ankylosing Spondylitis Disease Activity Score ≥ 2.1 at Screening and Baseline despite concurrent Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy, or intolerance/contraindication to NSAIDs.
• Objective signs of inflammation at Screening as defined by: Magnetic Resonance Imaging (MRI) of sacroiliac joints performed up to 3 months prior to screening showing acute inflammatory lesion(s), OR elevated quick C-reactive Protein (CRP) (\> 5 mg/L), OR MRI showing acute inflammatory lesion(s) in the sacroiliac joints and spine performed during screening period.
• Inadequate response to NSAIDs

You may not qualify if:

• Previous exposure to secukinumab or other biologic drug directly targeting Interleukin(IL)-17 or IL-17 receptor.
• Patients who have previously been treated with Tumor Necrosis Factor Alpha inhibitors (investigational or approved).
• Patients treated with any cell-depleting therapies.
• Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunosuppressed the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
• History of clinically significant liver disease or liver injury
• History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).
• Active systemic infections during the last 2 weeks (exception: common cold) prior to randomization.
• History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis (TB) infection
• Patients positive for human immunodeficiency virus, hepatitis B or hepatitis C
• Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (47)

Novartis Investigative Site

Nice, Cedex1, 06001, France

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Novartis Investigative Site

Limoges, Haute Vienne, 87000, France

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Novartis Investigative Site

Caluire-et-Cuire, 69300, France

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Novartis Investigative Site

Chambray-lès-Tours, 37170, France

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Novartis Investigative Site

Grenoble, 38043, France

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Novartis Investigative Site

La Roche-sur-Yon, 85925, France

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Novartis Investigative Site

Le Mans, 72000, France

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Novartis Investigative Site

Montpellier, 34295, France

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Novartis Investigative Site

Nantes, 44093, France

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Novartis Investigative Site

Orléans, 45100, France

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Novartis Investigative Site

Paris, 75013, France

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Novartis Investigative Site

Toulouse, 31059, France

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Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

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Novartis Investigative Site

Bad Doberan, 18209, Germany

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Novartis Investigative Site

Bad Pyrmont, 31812, Germany

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Novartis Investigative Site

Berlin, 12161, Germany

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Novartis Investigative Site

Berlin, 12163, Germany

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Novartis Investigative Site

Berlin, 13125, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Berlin, 14059, Germany

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Novartis Investigative Site

Bonn, 53105, Germany

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Novartis Investigative Site

Chemnitz, 09130, Germany

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Novartis Investigative Site

Cologne, 50937, Germany

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Novartis Investigative Site

Cottbus, 03042, Germany

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Novartis Investigative Site

Dresden, 01067, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Ehringshausen, 35630, Germany

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Novartis Investigative Site

Erlangen, 91056, Germany

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Novartis Investigative Site

Freiberg, 09599, Germany

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Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

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Novartis Investigative Site

Gera, 07548, Germany

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Novartis Investigative Site

Gommern, 39245, Germany

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Novartis Investigative Site

Hamburg, 20095, Germany

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Novartis Investigative Site

Hamburg, 22391, Germany

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Novartis Investigative Site

Hamburg, 22415, Germany

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Novartis Investigative Site

Herne, 44649, Germany

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Novartis Investigative Site

Hildesheim, 31134, Germany

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Novartis Investigative Site

Magdeburg, 39104, Germany

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Novartis Investigative Site

Magdeburg, 39110, Germany

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Novartis Investigative Site

Mainz, 55131, Germany

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Novartis Investigative Site

München, 80639, Germany

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Novartis Investigative Site

München, 81377, Germany

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Novartis Investigative Site

Potsdam, 14469, Germany

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Novartis Investigative Site

Ratingen, 40878, Germany

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Novartis Investigative Site

Rendsburg, 24768, Germany

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Novartis Investigative Site

Trier, 54292, Germany

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Novartis Investigative Site

Ulm, 89073, Germany

Location

Related Publications (1)

• Poddubnyy D, Hammel L, Heyne M, Veit J, Jentzsch C, Baraliakos X. Treat-to-target strategy with secukinumab as a first-line biological disease modifying anti-rheumatic drug compared to standard-of-care treatment in patients with active axial spondyloarthritis: protocol for a randomised open-label phase III study, AScalate. BMJ Open. 2020 Sep 30;10(9):e039059. doi: 10.1136/bmjopen-2020-039059.

  PMID: 32998926 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Axial Spondyloarthritis; Non-Radiographic Axial Spondyloarthritis

Interventions

secukinumab; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

(862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: April 8, 2019
• Study Start: June 4, 2019
• Primary Completion: February 4, 2022
• Study Completion: September 22, 2022
• Last Updated: April 29, 2025
• Results First Posted: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (13); DE (34)