Clinical trial NCT03906136: AScalate: Treat-to-target in Axial Spondyloarthritis
Official title: A Randomized, Open Label Multicenter Trial to Investigate the Efficacy of a Treat-to-target (T2T) Treatment Strategy With Secukinumab (AIN457) as a First-line Biologic Compared to a Standard-of-care (SOC) Treatment Over 36 Weeks in Patients With Active Axial Spondyloarthritis (axSpA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Keywords: axial spondyloarthritis
axSpA
treat-to-target
T2T
secukinumab
AIN457
Non-Radiographic Axial Spondyloarthritis
nr-axSpA
Radiographic Axial Spondyloarthritis
r-axSpA
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-04-08
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The study included an 8-week Screening period, a 36-week treatment period, and a 20-week safety follow-up period. Neither investigators nor patients were blinded. The primary endpoint was the percentage of patients achieving an ASAS40 response at Week 24. At Baseline, patients were randomized equally to one of two treatment groups (T2T or SOC).

Patients were evaluated every 12 weeks from Baseline through to Week 36. Safety evaluations were included in the regular visits; in addition, a safety follow-up visit was performed 20 weeks after the last study visit (i.e. Week 36) and took place at Week 56 for patients completing the study according to the protocol.

Patients assigned to the SOC treatment group received SOC treatment at the discretion of the investigator in accordance with current clinical practice.

Patients assigned to the T2T treatment group received first line biological treatment with secukinumab 150 mg. Responders were defined as those patients with an ASDAS clinically important improvement of ≥ 1.1.

At week 12 responders continued secukinumab 150 mg, whereas treatment was escalated to 300 mg for non-responders.

At week 24, disease activity was assessed again. Patients who qualify as responders continued the treatment they received prior (either secukinumab 150 mg or 300 mg), patients who were non-responders at week 24 were escalated in treatment: patients who received secukinumab 300 mg before were switched to Adalimumab, and patients who received secukinumab 150mg before were escalated to secukinumab 300mg.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Patients Achieving an ASAS40 Response at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Patients Achieving an ASAS40 Response at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Patients Achieving ASAS20 Response
timeFrame: Baseline, Weeks 12 and 24
measure: Percentage of Patients Achieving ASAS Partial Remission
timeFrame: Baseline, Weeks 12 and 24
measure: Percentage of Patients Meeting the Ankylosing Spondylitis Disease Activity Score (ASDAS) Definition of Inactive Disease
timeFrame: Baseline, Weeks 12 and 24
measure: Percentage of Patients With ASDAS Major Improvement
timeFrame: Baseline, Weeks 12 and 24
measure: Percentage of Patients With ASDAS Low Disease Activity
timeFrame: Baseline, Weeks 12 and 24
measure: Percentage of Patients Achieving the Bath Ankylosing Spondylitis Disease Activity Index Response 50% (BASDAI 50) at Week 12 and Week 24
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Chest Expansion
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in the ASQoL (Ankylosing Spondylitis Quality of Life Instrument)
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in ASAS-HI (Ankylosing Spondyloarthritis International Society Health Index)
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Global Disease Assessment (Patient)
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Global Disease Assessment (Physician)
timeFrame: Baseline, Weeks 12 and 24
Other outcomes:
Locations:
city: Nice
country: France
facility: Novartis Investigative Site
state: Cedex1
city: Limoges
country: France
facility: Novartis Investigative Site
state: Haute Vienne
city: Caluire et Cuire
country: France
facility: Novartis Investigative Site
city: Chambray les Tours
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: La Roche sur Yon Cedex
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Montpellier 5
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Orleans
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Bad Doberan
country: Germany
facility: Novartis Investigative Site
city: Bad Pyrmont
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Cottbus
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Ehringshausen
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiberg
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gera
country: Germany
facility: Novartis Investigative Site
city: Gommern
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Hildesheim
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Ratingen
country: Germany
facility: Novartis Investigative Site
city: Rendsburg
country: Germany
facility: Novartis Investigative Site
city: Trier
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.