A Phase III Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Active Ankylosing Spondylitis

A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Clinical Study to Evaluate the Efficacy and Safety of AK111 in the Treatment of Subjects With Active Ankylosing Spondylitis

This is a randomized, double-blind, placebo-controlled, multi-center phase III clinical study to evaluate the efficacy and safety of AK111 in the treatment of subjects with active ankylosing spondylitis.

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Drug: AK111; Drug: Placebo+AK111

Detailed Description

The study consists of 3 parts. Part 1 is screening period, Part 2 is Placebo control period and part 3 is Long term treatment follow-up period. The research period is 61 weeks in total.

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • 1006-The First Affiliated Hospital of Bengbu Medical University
    • Hefei, Anhui, China
      • 1038-Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • 1001-Peking University Third Hospital
    • Beijing, Beijing Municipality, China
      • 1002-Xuanwu Hospital Capital Medical University
    • Beijing, Beijing Municipality, China
      • 1042-Peking University Shougang Hospital
  • Fujian
    • Xiamen, Fujian, China
      • 1049-The First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China
      • 1027-Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • 1005-Nanfang Hospital
    • Guangzhou, Guangdong, China
      • 1025-Guangzhou First People's Hospital
    • Jieyang, Guangdong, China
      • 1030-Jieyang People's Hospital
    • Shenzhen, Guangdong, China
      • 1008-The Seventh Affiliated Hospital, Sun Yat-sen University
    • Shenzhen, Guangdong, China
      • 1026-Shenzhen People's Hospital
    • Zhongshan, Guangdong, China
      • 1056-Zhongshan Traditional Chinese Medicine Hospital
  • Guangxi
    • Liuchow, Guangxi, China
      • 1024-Liuzhou People's Hospital
    • Nanning, Guangxi, China
      • 1021-The People's Hospital of Guangxi Zhuang Autonomous Region
  • Hainan
    • Haikou, Hainan, China
      • 1022-The First Affiliated Hospital of Hainan Medical University
  • Hebei
    • Baoding, Hebei, China
      • 1034-Affiliated Hospital of Hebei University
    • Langfang, Hebei, China
      • 1012-Hebei Petro China Central Hospital
    • Shijiazhuang, Hebei, China
      • 1029-Hebei General Hospital
  • Heilongjiang
    • Qiqihar, Heilongjiang, China
      • 1033-The First Hospital of Qiqihar
  • Henan
    • Luoyang, Henan, China
      • 1045-The First Affiliated Hospital of Henan University of Science and Technology
    • Nanyang, Henan, China
      • 1053-Nanyang Central Hospital
  • Hubei
    • Shiyan, Hubei, China
      • 1051-Shiyan People's Hospital
  • Hunan
    • Hengyang, Hunan, China
      • 1031-The First Affiliated Hospital of University of South China
    • Yueyang, Hunan, China
      • 1032-Yueyang Central Hospital
    • Zhuzhou, Hunan, China
      • 1011-Zhuzhou Central Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China
      • 1017-Changzhou NO.2 People's Hospital
    • Lianyungang, Jiangsu, China
      • 1037-The Second People's Hospital of Lianyungang
    • Nanjing, Jiangsu, China
      • 1004-Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China
      • 1007-Nanjing Drum Tower Hospital
    • Nanjing, Jiangsu, China
      • 1036-Jiangsu Province Hospital
    • Nantong, Jiangsu, China
      • 1018-Affiliated Hospital of Nantong University
    • Wuxi, Jiangsu, China
      • 1035-Wuxi People's Hospital
    • Xuzhou, Jiangsu, China
      • 1013-Xuzhou Central Hospital
    • Zhenjiang, Jiangsu, China
      • 1014-Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • 1047-The First Affiliated Hospital of Gannan Medical College
    • Nanchang, Jiangxi, China
      • 1020-The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • 1039-The First Affiliated Hospital of Nanchang University
    • Pingxiang, Jiangxi, China
      • 1046-Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China
      • 1044-Jilin Provincial People's Hospital
  • Shandong
    • Jining, Shandong, China
      • 1028- Jining First People's Hospital
    • Linyi, Shandong, China
      • 1019-Linyi City People Hospital
    • Weifang, Shandong, China
      • 1055-Weifang People's Hospital
    • Zaozhuang, Shandong, China
      • 1016-Zaozhuang Municipal Hospital
  • Shanxi
    • Linfen, Shanxi, China
      • 1054-Linfen Central Hospital
    • Taiyuan, Shanxi, China
      • 1009-Second Hospital of Shanxi Medical University
    • Yuncheng, Shanxi, China
      • 1043-Yuncheng Central Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • 1010-West China Hospital,Sichuan University
    • Mianyang, Sichuan, China
      • 1048-Mianyang Central Hospital
    • Nanchong, Sichuan, China
      • 1041-Affiliated Hospital of North Sichuan Medical College
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • 1023-The People's Hospital of Xinjiang Uyghur Autonomous Region
  • Zhejiang
    • Huzhou, Zhejiang, China
      • 1040- Huzhou Third People's Hospital
    • Taizhou, Zhejiang, China
      • 1015-Taizhou Hospital of Zhejiang Province
    • Wenzhou, Zhejiang, China
      • 1050-The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female subjects aged ≥18 years old.
• Subjects with confirmed ankylosing spondylitis before screening.
• During screening and before randomization, BASDAI score ≥ 4, total back pain score≥ 4.
• Subjects received at least 2 kind of non-steroidal anti-inflammatory drugs (NSAIDs), prior to randomization with an inadequate response or failure to respond, or with contraindications or intolerance to the use of NSAIDs.
• Subjects who are regularly taking NSAIDs, weak opioids or oral glucocorticoids(The daily dose should be ≤10mg prednisone or equivalent dose of glucocorticoid) as part of their AS therapy are required to be on a stable dose for at least 14 days before randomization. If the drug has been discontinued, at least 2 weeks washout period is required before randomization.
• Subjects taking methotrexate (MTX) (≤25mg/week) or Sulfasalazine (≤3g/day) are allowed to continue their medication if started at least 12 weeks prior to baseline, with a stable dose for at least 4 weeks before randomization. If the drug has been discontinued, at least 4 weeks washout period is required before randomization.
• Subjects who are able to understand and voluntarily sign the ICF and complete the study procedure.

Exclusion Criteria:

• Subjects with symptom of pain that affected the evaluation of efficacy.
• Subjects with other inflammatory diseases or autoimmune diseases except Ankylosing spondylitis (AS).
• Subjects who are using strong opioid analgesics.
• Received glucocorticoid intramuscular or intravenous injection within 2 weeks prior to randomization; Received intraarticular or paraspinal glucocorticoid therapy within 4 weeks before randomization.
• Received other antirheumatic drugs (except methotrexate, sulfasalazine), proprietary Chinese medicine or traditional Chinese medicine decoction, JAK inhibitor treatment for AS within 4 weeks before randomization.
• Received Natalizumab or other B cell or T cell modulator in the 12 months prior to randomization.
• Previous exposure to secukinumab, ixekizumab or any other biologic drug directly targeting IL-17 or IL-17 receptor.
• Received multiple tumor necrosis factor α (TNF-α) inhibitors; The eluting period of biologics received before randomization is shorter than the protocol.
• Participated in a clinical study of any other drug or medical device within 1 month (≤30 days) prior to randomization, or last received the investigational drug within 5 half-lives.
• The presence of any other systemic disease or laboratory abnormalities that the investigator has judged unsuitable for clinical trials.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK111; AK111 150 mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week 48.	Drug: AK111; Drug: AK111 subcutaneous injection at week 0,1, 4 and 4-weekly thereafter until week 48.
Placebo Comparator: placebo; Placebo+AK111 placebo subcutaneous injection at week 0,1, 4,8 and 12 follow AK111 4-weekly thereafter until week 48.	Drug: Placebo+AK111; Placebo+AK111 placebo subcutaneous injection at week 0,1, 4,8 and 12 follow AK111 4-weekly thereafter until week 48.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the response rate of ASAS20	Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.	week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The response rate of ASAS40	Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16.	week 16
The response rate of ASAS20	Percentage of subjects who achieve ASAS20 response throughout the clinical trial	baseline to week 52
The response rate of ASAS40	Percentage of subjects who achieve ASAS40 response throughout the clinical trial	baseline to week 52
The response rate of ASAS5/6	Percentage of subjects who achieve ≥20% improvement in five of the six domains (ASAS5/6) response throughout the clinical trial	baseline to week 52
Change from baseline on the ASDAS-CRP	Change from baseline on the Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) at each visit from baseline	baseline to week 52
Change from baseline on the SF-36 PCS	Change from baseline on the Short-Form 36 physical component score(SF-36 PCS) at each visit from baseline	baseline, week 16 and week 52
Change from baseline on the ASQoL scores	Change from baseline on the Ankylosing Spondylitis Quality of Life (ASQoL) scores at each visit from baseline	baseline, week 16 and week 52
Treatment-emergent adverse events	Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study	baseline to week 52
Serious adverse events	Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study	baseline to week 52
Clinically significant examination results	Recording clinically significant examination results	baseline to week 52

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Actual): February 19, 2025
• Study Completion (Actual): November 7, 2025

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Axial Spondyloarthritis; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Spinal Diseases; Spondylarthropathies; Ankylosis; Spondylarthritis; Spondylitis; Spondylitis, Ankylosing
• Other Study ID Numbers: AK111-303

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