Clinical trial NCT05467995: A Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Active Ankylosing Spondylitis
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Active Ankylosing Spondylitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ankylosing Spondylitis
Keywords: AK111
Ankylosing Spondylitis
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2022-07-21
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of AK111 in subjects with active ankylosing spondylitis.

Detailed description: The purpose of this study is to evaluate the efficacy and safety of AK111 in the treatment of subjects with active ankylosing spondylitis. Subjects will be randomized to receive AK111 or placebo following subcutaneous injection. The study period for each subject will be 25 weeks, including a screening period of up to 35 days, followed by a treatment period of 12 weeks and a follow up period of 8 weeks.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects aged 18-75 years old.
* Ankylosing spondylitis has been diagnosed for at least 6 months before screening, with radiological evidence that meets the Modified New York Criteria for Ankylosing Spondylitis.
* Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 and Spinal pain score≥ 4 (based on BASDAI question 2).
* Subjects received at least 1 kind of non-steroidal anti-inflammatory drugs (NSAIDs), prior to randomization with an inadequate response or failure to respond.
* Subjects who are regularly taking NSAIDs, weak opioids or oral glucocorticoids as part of their AS therapy are required to be on a stable dose for at least 14 days 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.

Exclusion Criteria:

* Subjects with total ankylosis of the spine.
* Subjects with progressive or uncontrolled diseases of respiratory, circulatory, digestive, urogenital, endocrine, nervous or mental systems, or with other chronic diseases that are not suitable to participate to the study.
* Subjects with other inflammatory diseases or autoimmune diseases except Ankylosing spondylitis (AS).
* Subjects with any severe systemic or local infection within 2 months before screening.
* Subjects who are using strong opioid analgesics.
* Combined use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) other than methotrexate and sulfasalazine, including but not limited to thalidomide, iguratimod, etc. within 4 weeks before randomization.
* Received any live vaccine within 2 months before screening or planned to receive any live vaccine during the study period.
* Previous exposure to secukinumab, ixekizumab or any other biologic drug directly targeting IL-17 or IL-17 receptor.
* Received Natalizumab or other drugs that regulate B cells or T cells within 6 months before screening.
* Received more than 2 kinds of Tumor necrosis factor alpha(TNF-α) inhibitors before screening.

Primary outcomes:
measure: Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.
timeFrame: Week16
measure: Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.
timeFrame: Baseline to Week20
measure: Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.
timeFrame: Baseline to Week20
Secondary outcomes:
measure: Percentage of subjects who achieve SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16.
timeFrame: Week 16
measure: Percentage of subjects who achieve ASAS20 response at each visit from baseline.
timeFrame: Baseline to Week 20
measure: Percentage of subjects who achieve ASAS40 at each visit from baseline.
timeFrame: Baseline to Week 20
measure: Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at each visit from baseline.
timeFrame: Baseline to Week 20
measure: pharmacodynamics(PD) parameters: Changes of Interleukin-17A (IL-17A) level in peripheral serum compared with baseline and its relationship with AK111 exposure.
timeFrame: Baseline to Week 20
measure: Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).
timeFrame: Baseline to Week 20
measure: Change from baseline on the 36-item Short-Form (SF-36) Health Survey at each visit from baseline.
timeFrame: Baseline to Week 20
measure: Area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t)
timeFrame: Baseline to Week 20
measure: Maximum observed concentration (Cmax)
timeFrame: Baseline to Week 20
measure: Terminal elimination half-life (T1/2)
timeFrame: Baseline to Week 20
measure: Time of occurrence of Cmax (Tmax)
timeFrame: Baseline to Week 20
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of Bengbu medical college
state: Anhui
city: Beijing
country: China
facility: Peking university people's hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Shougang hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Xuanwu hospital capital medical university
state: Beijing
city: Guangzhou
country: China
facility: Guangdong provincial people's hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: The first affiliated hospital of Zhengzhou University
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The first Bethune hospital of Jilin university
state: Jilin
city: Taiyuan
country: China
facility: Second hospital of Shanxi Medical university
state: Shanxi
city: Shenzhen
country: China
facility: The seventh affiliated hospital, Sun Yat-sen university
state: Shenzhen
Study officials:
References: