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

Novartis

Status and phase: Completed; Phase 3

Conditions: Non-radiographic Spondyloarthritis

Treatments: Drug: Placebo; Drug: Secukinumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02696031

CAIN457H2315

Details and patient eligibility

About

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

Full description

Patients were randomized to one of three treatment groups (1:1:1) in the core phase:

Secukinumab 150 mg Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4 Secukinumab 150 mg No Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4 Placebo: placebo (1 mL) s.c. PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4.

All patients received secukinumab 150 mg as open-label treatment from Week 52 up to Week 100, unless they had discontinued study treatment.

At Week 104, all patients who finished the core phase according to the protocol were asked to continue in an optional, exploratory extension phase. Patients who achieved ASAS20 response at Week 104 (Core Phase Responders) were randomized to the following treatment groups (blinded) in the extension phase:

Core Phase Responder 150 mg: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS and placebo (1 mL) s.c. PFS every four weeks; Core Phase Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks.

Core Phase Non-Responders (not achieving ASAS20 at Week 104) were escalated to secukinumab 300 mg in an open-label manner.

• Core Phase Non-Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks open-label.

Starting from Week 156 onward, a patient could switch to secukinumab 300 mg open-label based on the clinical judgment of disease activity by the investigator.

Enrollment: 555 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or non-pregnant, non-nursing female patients at least 18 years of age
• Diagnosis of axial spondyloarthritis according to Ankylosing SpondyloArthritis International Society (ASAS) axial spondyloarthritis criteria
• objective signs of inflammation (magnetic resonance imaging (MRI) or abnormal C-reactive protein)
• active axial spondyloarthritis as assessed by total Bath Ankylosing Spondylitis Disease Activity Index >=4 cm
• Spinal pain as measured by Bath Ankylosing Spondylitis Disease Activity Index question #2 ≥ 4 cm (0-10 cm) at baseline
• Total back pain as measured by Visual Analogue scale ≥ 40 mm (0-100 mm) at baseline
• Patients should have been on at least 2 different non-steroidal anti-inflammatory drugs with an inadequate response
• Patients who have been on a Tumor Necrosis Factor (TNF) α inhibitor (not more than one) must have experienced an inadequate response

Exclusion criteria

• Patients with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally
• Inability or unwillingness to undergo MRI
• Chest X-ray or MRI with evidence of ongoing infectious or malignant process
• Patients taking high potency opioid analgesics
• Previous exposure to secukinumab or any other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor
• Pregnant or nursing (lactating) women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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555 participants in 6 patient groups, including a placebo group

Secukinumab, 150 mg Load (Core phase)

Experimental group

Description:

Secukinumab 150 mg s.c., pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4, Load, Core phase

Treatment:

Drug: Secukinumab

Secukinumab, 150 mg No Load (Core phase)

Experimental group

Description:

Secukinumab 150 mg s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4, No Load, Core phase

Treatment:

Drug: Secukinumab

Placebo (Core phase)

Placebo Comparator group

Description:

Placebo s.c., PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4, Core phase

Treatment:

Drug: Placebo

Core Phase Responder 150 mg (Extension phase)

Experimental group

Description:

Core Phase Responder 150 mg blinded: secukinumab 150 mg s.c. PFS and placebo (1 mL) s.c. PFS every four weeks, in the Extension phase

Treatment:

Drug: Secukinumab

Drug: Placebo

Core Phase Responder 300 mg (Extension phase)

Experimental group

Description:

Core Phase Responder 300 mg blinded: 2 injections with secukinumab 150 mg s.c. PFS every four weeks, in the Extension phase

Treatment:

Drug: Secukinumab

Core Phase Non-Responder 300 mg (Extension phase)

Experimental group

Description:

Core Phase Non-Responder 300 mg: 2 injections with secukinumab 150 mg s.c. PFS every four weeks open-label, in the Extension phase

Treatment:

Drug: Secukinumab