Clinical trial NCT06378697: A Phase III Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Active Ankylosing Spondylitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ankylosing Spondylitis
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-04-22
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: the response rate of ASAS20
timeFrame: week 16
Secondary outcomes:
measure: The response rate of ASAS40
timeFrame: week 16
measure: The response rate of ASAS20
timeFrame: baseline to week 52
measure: The response rate of ASAS40
timeFrame: baseline to week 52
measure: The response rate of ASAS5/6
timeFrame: baseline to week 52
measure: Change from baseline on the ASDAS-CRP
timeFrame: baseline to week 52
measure: Change from baseline on the SF-36 PCS
timeFrame: baseline, week 16 and week 52
measure: Change from baseline on the ASQoL scores
timeFrame: baseline, week 16 and week 52
measure: Treatment-emergent adverse events
timeFrame: baseline to week 52
measure: Serious adverse events
timeFrame: baseline to week 52
measure: Clinically significant examination results
timeFrame: baseline to week 52
Other outcomes:
Locations:
city: Bengbu
country: China
facility: 1006-The First Affiliated Hospital of Bengbu Medical University
state: Anhui
city: Hefei
country: China
facility: 1038-Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: 1001-Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: 1002-Xuanwu Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: 1042-Peking University Shougang Hospital
state: Beijing
city: Xiamen
country: China
facility: 1049-The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: 1027-Lanzhou University Second Hospital
state: Gansu
city: Guangzhou
country: China
facility: 1005-Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: 1025-Guangzhou First People's Hospital
state: Guangdong
city: Jieyang
country: China
facility: 1030-Jieyang People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: 1008-The Seventh Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Shenzhen
country: China
facility: 1026-Shenzhen People's Hospital
state: Guangdong
city: Zhongshan
country: China
facility: 1056-Zhongshan Traditional Chinese Medicine Hospital
state: Guangdong
city: Liuzhou
country: China
facility: 1024-Liuzhou People's Hospital
state: Guangxi
city: Nanning
country: China
facility: 1021-The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Haikou
country: China
facility: 1022-The First Affiliated Hospital of Hainan Medical University
state: Hainan
city: Baoding
country: China
facility: 1034-Affiliated Hospital of Hebei University
state: Hebei
city: Langfang
country: China
facility: 1012-Hebei Petro China Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: 1029-Hebei General Hospital
state: Hebei
city: Qiqihar
country: China
facility: 1033-The First Hospital of Qiqihar
state: Heilongjiang
city: Luoyang
country: China
facility: 1045-The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: 1053-Nanyang Central Hospital
state: Henan
city: Shiyan
country: China
facility: 1051-Shiyan People's Hospital
state: Hubei
city: Hengyang
country: China
facility: 1031-The First Affiliated Hospital of University of South China
state: Hunan
city: Yueyang
country: China
facility: 1032-Yueyang Central Hospital
state: Hunan
city: Zhuzhou
country: China
facility: 1011-Zhuzhou Central Hospital
state: Hunan
city: Changzhou
country: China
facility: 1017-Changzhou NO.2 People's Hospital
state: Jiangsu
city: Lianyungang
country: China
facility: 1037-The Second People's Hospital of Lianyungang
state: Jiangsu
city: Nanjing
country: China
facility: 1004-Zhongda Hospital Southeast University
state: Jiangsu
city: Nanjing
country: China
facility: 1007-Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: 1036-Jiangsu Province Hospital
state: Jiangsu
city: Nantong
country: China
facility: 1018-Affiliated Hospital of Nantong University
state: Jiangsu
city: Wuxi
country: China
facility: 1035-Wuxi People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: 1013-Xuzhou Central Hospital
state: Jiangsu
city: Zhenjiang
country: China
facility: 1014-Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Ganzhou
country: China
facility: 1047-The First Affiliated Hospital of Gannan Medical College
state: Jiangxi
city: Nanchang
country: China
facility: 1020-The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: 1039-The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Pingxiang
country: China
facility: 1046-Pingxiang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: 1044-Jilin Provincial People's Hospital
state: Jilin
city: Jining
country: China
facility: 1028- Jining First People's Hospital
state: Shandong
city: Linyi
country: China
facility: 1019-Linyi City People Hospital
state: Shandong
city: Weifang
country: China
facility: 1055-Weifang People's Hospital
state: Shandong
city: Zaozhuang
country: China
facility: 1016-Zaozhuang Municipal Hospital
state: Shandong
city: Linfen
country: China
facility: 1054-Linfen Central Hospital
state: Shanxi
city: Taiyuan
country: China
facility: 1009-Second Hospital of Shanxi Medical University
state: Shanxi
city: Yuncheng
country: China
facility: 1043-Yuncheng Central Hospital
state: Shanxi
city: Chengdu
country: China
facility: 1010-West China Hospital,Sichuan University
state: Sichuan
city: Mianyang
country: China
facility: 1048-Mianyang Central Hospital
state: Sichuan
city: Nanchong
country: China
facility: 1041-Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Urumqi
country: China
facility: 1023-The People's Hospital of Xinjiang Uyghur Autonomous Region
state: Xinjiang
city: Huzhou
country: China
facility: 1040- Huzhou Third People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: 1015-Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: 1050-The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
References: