Non-radiographic Axial Spondyloarthritis
Conditions
Keywords
nr-AxSpa, non-radiographic axial Spondyloarthritis, Secukinumab, remission, withdrawal, inflammatory back pain, sacroiliitis, AIN457
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.
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.
Interventions
DRUGSecukinumab
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.
DRUGPlacebo
Treatment Period 2: Double-blind placebo PFS s.c. every 4 weeks from Week 56 to Week 116.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This phase IV, multicenter study uses a double-blind, placebo-controlled, randomized withdrawal design (Treatment Period 2) preceded by an open label lead-in period (Treatment Period 1).
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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: 1. Inflammatory back pain for at least 6 months 2. Onset before 45 years of age 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Belgium, Brazil, Colombia, Czechia, France, Germany, Hungary, Israel, Italy, Malaysia, Mexico, Netherlands, Philippines, Poland, Romania, Thailand, Turkey (Türkiye), Vietnam
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed