A Study of Secukinumab to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission
Study Details
Study Description
Brief Summary
This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with Non-radiographic axial spondyloarthritis, (nr-axSpA) who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response (ASDAS-CRP < 1.3). Maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Detailed Description
This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with nr-axSpA who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response Inactive Disease (ID) response (ASDAS-CRP < 1.3). The maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120.
Study treatment will be as follows:
-
Open-label Secukinumab PFS (prefilled syringe) will be labeled as AIN457 150mg/1mL
-
Double-blind Secukinumab and Placebo PFS will be labeled as AIN457 150mg/1mL/Placebo.
Study duration will be up to 128 weeks from Baseline.
The treatment duration will be up to 120 weeks with last treatment administration at Week 116.
In the Treatment Period 1 participant will attend a site visit approximately 1 month after Baseline and approximately every 12 weeks thereafter. In the Treatment Period 2 participant will attend site visits approximately every 4 weeks.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment Period 1 Open-label Secukinumab PFS (prefilled syringe) labeled as AIN457 150mg/1mL |
Drug: Secukinumab
Treatment Period 1: Open-label secukinumab 150 mg PFS s.c. at baseline, Weeks 1, 2, 3 and 4 followed by administration every four weeks up to Week 52.
|
Experimental: Treatment Period 2 Double-blind Secukinumab and Placebo PFS labeled as AIN457 150mg/1mL/Placebo |
Drug: Placebo
Treatment Period 2: Double-blind placebo PFS s.c. every 4 weeks from Week 56 to Week 116.
Drug: Secukinumab
Treatment Period 2: Double-blind secukinumab 150 mg PFS s.c. every 4 weeks from Week 56 to Week 116.
Escape re-treatment (during Treatment Period 2): Open-label secukinumab 150 mg PFS s.c.
|
Outcome Measures
Primary Outcome Measures
- The proportion of participants remaining flare-free during Treatment Period 2 [Week 120]
The primary efficacy endpoint is the proportion of participants in the randomized withdrawal population remaining flare-free at Week 120. A flare is defined as ASDAS-CRP ≥ 2.1 at 2 consecutive visits, or ASDAS-CRP > 3.5 at any visit during Treatment Period 2, starting at Week 60. Parameters used for ASDAS-CRP include: Spinal pain (BASDAI question 2), Patient's global assessment of disease activity, Peripheral pain/swelling (BASDAI question 3), Duration of morning stiffness (BASDAI question 6) C-reactive protein (CRP) in mg/L
Secondary Outcome Measures
- Time to flare during Treatment Period 2 [From Week 56 to Week 120]
A flare is defined as ASDAS-CRP ≥ 2.1 at 2 consecutive visits, or ASDAS-CRP > 3.5 at any visit during Treatment Period 2, starting at Week 60.
- Number of participants with Adverse Events [From Baseline to Week 128]
Safety and tolerability demonstrated by assessing: - Adverse events (AEs) and serious adverse events (SAEs)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or non-pregnant, non-lactating female participants at least 18 years of age
-
Clinical diagnosis of axSpA AND according to ASAS axSpA criteria:
-
Inflammatory back pain for at least 6 months
-
Onset before 45 years of age
-
Sacroiliitis on MRI (magnetic resonance imaging) (as assessed by central reader) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features
-
Objective signs of inflammation at screening, evident by either MRI with Sacroiliac Joint inflammation (as assessed by central reader) AND / OR hsCRP > ULN (as defined by the central lab)
-
Active axSpA as assessed by total BASDAI ≥ 4 cm (0-10 cm) at baseline.
-
Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline.
-
Total back pain as measured by VAS (visual analog scale) ≥ 40 mm (0-100 mm) at baseline.
-
Participants should have been on at least 2 different NSAIDs (non-steroidal anti-inflammatory drugs) at the highest recommended dose for at least 4 weeks in total prior to baseline with an inadequate response or failure to respond, or less if therapy had to be withdrawn due to intolerance, toxicity or contraindications.
Exclusion Criteria:
-
Participants with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally (radiological criterion according to the modified New York diagnostic criteria for AS) as assessed by central reader.
-
Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine).
-
Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor or previous treatment with immunomodulatory biologic agents including those targeting TNFα (tumor necrosis factor α) (unless participants discontinued the treatment with TNFα inhibitor due to a reason other than efficacy [primary or secondary lack of efficacy, inadequate response] and only after appropriate wash-out period prior to baseline was observed).
-
History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
-
Active ongoing inflammatory diseases other than nr-axSpA that might confound the evaluation of the benefit of secukinumab therapy, including uveitis.
-
Active inflammatory bowel disease.
-
History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAIN457I2401
- 2022-001153-23