A Study of KHK4827 in Subjects With Axial Spondyloarthritis (axSpA)

Study Overview
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Brief Summary
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To evaluate the efficacy of KHK4827 in axSpA (ankylosing spondylitis [AS] and non-radiographic axial spondyloarthritis [nr-axSpA]) subjects compared to placebo, as measured by the proportion of axSpA subjects achieving an Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 16.

Official Title
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A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study With an Open Label Extension to Evaluate the Efficacy and Safety of KHK4827 in Subjects With Axial Spondyloarthritis

Conditions
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Axial Spondyloarthritis

Intervention / Treatment
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* Drug: KHK4827
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with age at onset <45 years and continuous chronic back pain for ≥ 3 months fulfills the ASAS classification criteria of axial spondyloarthritis (with the exception of the Crohn's disease) Subject has Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at screening and enrollment Subject has spinal pain score (BASDAI question #2) ≥ 4 at screening and enrollment Subject has had adequate therapy with non-steroidal anti-inflammatory drugs (oral NSAIDs) for back pain for at least 3 months with inadequate treatment response before enrollment Exclusion Criteria: Complete ankylosis (fusion) of the spine Subject with active ongoing inflammatory diseases other than axSpA that might confound the evaluation of KHK4827 therapy, including reactive arthritis, spondyloarthritis associated with inflammatory bowel disease, SAPHO syndrome (pustulotic arthro-osteitis), fibromyalgia, ankylosing spinal hyperostosis, osteitis condensans ilii, spondylosis deformans, or osteoarthritis sacroiliac joint disease Subject has a prior history of >1 anti-TNF therapy Subject has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the Columbia-Suicide Severity Rating Scale (C-SSRS) at enrollment Subject has a history or evidence of a psychiatric disorder, alcohol and/or substance abuse Subject has severe depression based on a total score of ≥ 15 on the Patient Health Questionnaire-8 (PHQ-8) at enrollment (note: subjects with a total score of 10 to 14 on the PHQ-8 should be referred to a mental health care professional)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KHK4827<br>KHK4827 administered SC | Drug: KHK4827<br>* Administered KHK4827 by subcutaneous (SC) injection until week 66.<br>* Other names: Brodalumab;|
| Placebo Comparator: Placebo<br>Placebo administered SC | Drug: Placebo<br>* Administered Placebo by subcutaneous (SC) injection until week 16. Administered KHK4827 by SC injection from week 17 until week 66.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of ASAS 40 in axSpA subjects |  | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of ASAS 40 in AS subjects |  | Week 16 | 
| Percentage of ASAS 40 in nr-axSpA subjects |  | Week 16 | 
| Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP change from baseline in axSpA subjects |  | Week 16 | 
| Number of adverse events |  | Up to week 68 | 
| Number of patients exposed to anti-KHK4827 antibodies |  | Pre-dose,Week 16,Week 32,Week 48,Week 68 or End of study | 
| Serum KHK4827 concentration |  | pre-dose、Week 1、Week 2、Week 4、Week 8、Week 12、Week 14、Week 16、Week 24、Week 28、Week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brodalumab, KHK4827, Axial Spondyloarthritis