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

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

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.

Study Overview

• Status: Completed
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Drug: KHK4827; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Fujita Health University Hpspital
  • Chiba, Japan
    • Tokyo Women's Medical University Yachiyo Medical Center
  • Fukuoka, Japan
    • Fukuoka University Hospital
  • Fukuoka, Japan
    • Chihaya Hospital
  • Fukuoka, Japan
    • Kyusyu University Hospital
  • Hokkaido, Japan
    • Hokkaido University Hospital
  • Hokkaido, Japan
    • Katayama Seikeigeka Rheumatism Clinic
  • Hyogo, Japan
    • Hyogo College of Medicine
  • Kagawa, Japan
    • Kagawa University Hospital
  • Kochi, Japan
    • Kochi Medical School Hospital
  • Nagasaki, Japan
    • Sasebo Chuo Hospital
  • Nara, Japan
    • Tenri Hospital
  • Okayama, Japan
    • Okayama Saiseikai Outpatient Centerl Hospital
  • Okinawa, Japan
    • Okinawa prefectural Chubu Hospital
  • Okinawa, Japan
    • Tomishiro Central Hospital
  • Osaka, Japan
    • Osaka City General Hospital
  • Osaka, Japan
    • Osaka University Hospital
  • Osaka, Japan
    • National Hosptal Organization Osaka Minami Medical Center
  • Osaka, Japan
    • Osaka City University Hospital
  • Osaka, Japan
    • Yukioka Hospital
  • Tokyo, Japan
    • Toho University Ohashi Medical Center
  • Tokyo, Japan
    • Juntendo University Hospital
  • Tokyo, Japan
    • St.Luke's International Hospital
  • Tokyo, Japan
    • Toho University Omori Medical Center
  • Tokyo, Japan
    • Tokyo Women's Medical University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of
    • Pusan National University Hospital
  • Daegu, Korea, Republic of
    • Daegu Catholic University Medical Center
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Gwangju, Korea, Republic of
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of
    • Ajou University Hospital
  • Gyeonggi-do, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of
    • The Catholic University of Korea Seoul St.Mary's Hospital
  • Seoul, Korea, Republic of
    • KyungHee University Hospital
  • Seoul, Korea, Republic of
    • Hanyang University Seoul Hospital
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • Kaohsiung, Taiwan
    • Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Cathay General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered SC	Drug: Placebo; Administered Placebo by subcutaneous (SC) injection until week 16. Administered KHK4827 by SC injection from week 17 until week 66.
Experimental: KHK4827; KHK4827 administered SC	Drug: KHK4827; Administered KHK4827 by subcutaneous (SC) injection until week 66.; Other Names: Brodalumab

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Publications and helpful links

General Publications

• Kim TH, Kishimoto M, Wei JC, Jeong H, Nozaki A, Kobayashi S; 4827-006 study group. Brodalumab, an anti-interleukin-17 receptor A monoclonal antibody, in axial spondyloarthritis: 68-week results from a phase 3 study. Rheumatology (Oxford). 2022 Sep 21:keac522. doi: 10.1093/rheumatology/keac522. Online ahead of print.
• Wei JC, Kim TH, Kishimoto M, Ogusu N, Jeong H, Kobayashi S; 4827-006 study group. Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial. Ann Rheum Dis. 2021 Aug;80(8):1014-1021. doi: 10.1136/annrheumdis-2020-219406. Epub 2021 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2017
• Primary Completion (Actual): September 23, 2019
• Study Completion (Actual): September 23, 2019

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimate): December 7, 2016

Study Record Updates

• Last Update Posted (Actual): March 3, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: KHK4827; Axial Spondyloarthritis; Brodalumab
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Spondylitis; Spondylarthritis; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: 4827-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No