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

Phase 3
Recruiting
Conditions
Ankylosing Spondylitis
Interventions
Drug: Placebo+AK111
Registration Number
NCT06378697
Lead Sponsor
Akeso
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
510
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AK111AK111AK111 150 mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week 48.
placeboPlacebo+AK111Placebo+AK111 placebo subcutaneous injection at week 0,1, 4,8 and 12 follow AK111 4-weekly thereafter until week 48.
Primary Outcome Measures
NameTimeMethod
the response rate of ASAS20week 16

Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.

Secondary Outcome Measures
NameTimeMethod
The response rate of ASAS20baseline to week 52

Percentage of subjects who achieve ASAS20 response throughout the clinical trial

Change from baseline on the SF-36 PCSbaseline, week 16 and week 52

Change from baseline on the Short-Form 36 physical component score(SF-36 PCS) at each visit from baseline

The response rate of ASAS40baseline to week 52

Percentage of subjects who achieve ASAS40 response throughout the clinical trial

Change from baseline on the ASDAS-CRPbaseline to week 52

Change from baseline on the Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) at each visit from baseline

Change from baseline on the ASQoL scoresbaseline, week 16 and week 52

Change from baseline on the Ankylosing Spondylitis Quality of Life (ASQoL) scores at each visit from baseline

Treatment-emergent adverse eventsbaseline to week 52

Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study

Serious adverse eventsbaseline to week 52

Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study

Clinically significant examination resultsbaseline to week 52

Recording clinically significant examination results

The response rate of ASAS5/6baseline to week 52

Percentage of subjects who achieve ≥20% improvement in five of the six domains (ASAS5/6) response throughout the clinical trial

Trial Locations

Locations (54)

1027-Lanzhou University Second Hospital

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Lanzhou, Gansu, China

1005-Nanfang Hospital

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Guangzhou, Guangdong, China

1030-Jieyang People's Hospital

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Jieyang, Guangdong, China

1008-The Seventh Affiliated Hospital, Sun Yat-sen University

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Shenzhen, Guangdong, China

1024-Liuzhou People's Hospital

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Liuzhou, Guangxi, China

1021-The People's Hospital of Guangxi Zhuang Autonomous Region

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Nanning, Guangxi, China

1034-Affiliated Hospital of Hebei University

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Baoding, Hebei, China

1012-Hebei Petro China Central Hospital

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Langfang, Hebei, China

1029-Hebei General Hospital

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Shijiazhuang, Hebei, China

1033-The First Hospital of Qiqihar

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Qiqihar, Heilongjiang, China

1045-The First Affiliated Hospital of Henan University of Science and Technology

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Luoyang, Henan, China

1011-Zhuzhou Central Hospital

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Zhuzhou, Hunan, China

1017-Changzhou NO.2 People's Hospital

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Changzhou, Jiangsu, China

1037-The Second People's Hospital of Lianyungang

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Lianyungang, Jiangsu, China

1035-Wuxi People's Hospital

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Wuxi, Jiangsu, China

1013-Xuzhou Central Hospital

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Xuzhou, Jiangsu, China

1014-Affiliated Hospital of Jiangsu University

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Zhenjiang, Jiangsu, China

1047-The First Affiliated Hospital of Gannan Medical College

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Ganzhou, Jiangxi, China

1020-The Second Affiliated Hospital of Nanchang University

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Nanchang, Jiangxi, China

1028- Jining First People's Hospital

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Jining, Shandong, China

1009-Second Hospital of Shanxi Medical University

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Taiyuan, Shanxi, China

1010-West China Hospital,Sichuan University

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Chengdu, Sichuan, China

1026-Shenzhen People's Hospital

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Shenzhen, Guangdong, China

1056-Zhongshan Traditional Chinese Medicine Hospital

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Zhongshan, Guangdong, China

1025-Guangzhou First People's Hospital

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Guangzhou, Guangdong, China

1001-Peking University Third Hospital

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Beijing, Beijing, China

1002-Xuanwu Hospital Capital Medical University

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Beijing, Beijing, China

1031-The First Affiliated Hospital of University of South China

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Hengyang, Hunan, China

1036-Jiangsu Province Hospital

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Nanjing, Jiangsu, China

1004-Zhongda Hospital Southeast University

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Nanjing, Jiangsu, China

1007-Nanjing Drum Tower Hospital

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Nanjing, Jiangsu, China

1039-The First Affiliated Hospital of Nanchang University

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Nanchang, Jiangxi, China

1043-Yuncheng Central Hospital

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Yuncheng, Shanxi, China

1006-The First Affiliated Hospital of Bengbu Medical University

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Bengbu, Anhui, China

1038-Anhui Provincial Hospital

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Hefei, Anhui, China

1049-The First Affiliated Hospital of Xiamen University

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Xiamen, Fujian, China

1042-Peking University Shougang Hospital

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Beijing, Beijing, China

1022-The First Affiliated Hospital of Hainan Medical University

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Haikou, Hainan, China

1053-Nanyang Central Hospital

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Nanyang, Henan, China

1051-Shiyan People's Hospital

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Shiyan, Hubei, China

1032-Yueyang Central Hospital

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Yueyang, Hunan, China

1018-Affiliated Hospital of Nantong University

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Nantong, Jiangsu, China

1044-Jilin Provincial People's Hospital

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Changchun, Jilin, China

1046-Pingxiang People's Hospital

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Pingxiang, Jiangxi, China

1019-Linyi City People Hospital

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Linyi, Shandong, China

1055-Weifang People's Hospital

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Weifang, Shandong, China

1016-Zaozhuang Municipal Hospital

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Zaozhuang, Shandong, China

1054-Linfen Central Hospital

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Linfen, Shanxi, China

1048-Mianyang Central Hospital

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Mianyang, Sichuan, China

1023-The People's Hospital of Xinjiang Uyghur Autonomous Region

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Urumqi, Xinjiang, China

1041-Affiliated Hospital of North Sichuan Medical College

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Nanchong, Sichuan, China

1040- Huzhou Third People's Hospital

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Huzhou, Zhejiang, China

1050-The First Affiliated Hospital of Wenzhou Medical University

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Wenzhou, Zhejiang, China

1015-Taizhou Hospital of Zhejiang Province

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Taizhou, Zhejiang, China

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