AScalate: Treat-to-target in Axial Spondyloarthritis

Novartis

Status and phase: Completed; Phase 3

Conditions: Axial Spondyloarthritis

Treatments: Other: Standard-of-care; Biological: Secukinumab/Adalimumab-Biosimilar

Study type: Interventional

Funder types: Industry

Identifiers

NCT03906136

2018-003882-32 (EudraCT Number)

CAIN457HDE01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 304 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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304 participants in 2 patient groups

TREAT-TO-TARGET (T2T)

Experimental group

Description:

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).

Treatment:

Biological: Secukinumab/Adalimumab-Biosimilar

Standard-of-care (SOC)

Active Comparator group

Description:

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.

Treatment:

Other: Standard-of-care