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

Ankylosing Spondylitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05467995
• Other study ID #: AK111-202
• Status: Completed
• Phase: Phase 2
• Start date: June 2, 2021
• Est. completion date: May 19, 2022

Study information

• Verified date: March 2024
• Source: Akeso
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: May 19, 2022
• Est. primary completion date: April 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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-a) inhibitors before screening.

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Biological:
• AK111
AK111 administered subcutaneously at Week 0, 1, and 4, then every 4 weeks
• Placebo
Placebo administered subcutaneously at Week 0, 1, and 4, then every 4 weeks

Locations

Country	Name	City	State
China	Peking university people's hospital	Beijing	Beijing
China	Peking University Shougang hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Xuanwu hospital capital medical university	Beijing	Beijing
China	The first affiliated hospital of Bengbu medical college	Bengbu	Anhui
China	The first Bethune hospital of Jilin university	Changchun	Jilin
China	Guangdong provincial people's hospital	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower hospital	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	The seventh affiliated hospital, Sun Yat-sen university	Shenzhen	Shenzhen
China	Second hospital of Shanxi Medical university	Taiyuan	Shanxi
China	The first affiliated hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Akeso

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global, pain, function (assessed by BASFI) and inflammation (mean of Ankylosing Spondylitis Disease Activity Index [BASDAI] question 5 and 6 ). ASAS20 response is defined as improvement of = 20% and =1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of =20% and =1 unit in the remaining domain.	Week16
Primary	Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.		Baseline to Week20
Primary	Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.		Baseline to Week20
Secondary	Percentage of subjects who achieve SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16.	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global, pain, function (assessed by BASFI) and inflammation (mean of Ankylosing Spondylitis Disease Activity Index [BASDAI] question 5 and 6 ). ASAS40 response is defined as improvement of =40% and =2 units in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening in the remaining domain.	Week 16
Secondary	Percentage of subjects who achieve ASAS20 response at each visit from baseline.	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global, pain, function (assessed by BASFI) and inflammation (mean of Ankylosing Spondylitis Disease Activity Index [BASDAI] question 5 and 6 ). ASAS20 response is defined as improvement of = 20% and =1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of =20% and =1 unit in the remaining domain.	Baseline to Week 20
Secondary	Percentage of subjects who achieve ASAS40 at each visit from baseline.	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global, pain, function (assessed by BASFI) and inflammation (mean of Ankylosing Spondylitis Disease Activity Index [BASDAI] question 5 and 6 ). ASAS40 response is defined as improvement of =40% and =2 units in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening in the remaining domain.	Baseline to Week 20
Secondary	Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at each visit from baseline.	The Ankylosing Spondylitis Quality of Life (ASQoL), a validated disease-specific 18-item questionnaire, has been developed specifically for measuring health-related quality of life (HRQoL) in subjects with ankylosing spondylitis (AS) . The ASQoL score ranges from 0 to 18 with a higher score indicating worse HRQoL.	Baseline to Week 20
Secondary	pharmacodynamics(PD) parameters: Changes of Interleukin-17A (IL-17A) level in peripheral serum compared with baseline and its relationship with AK111 exposure.		Baseline to Week 20
Secondary	Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).		Baseline to Week 20
Secondary	Change from baseline on the 36-item Short-Form (SF-36) Health Survey at each visit from baseline.	The SF-36 is a 36-item generic health status measure. It measures 8 general health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health. Each of the 8 domain scores and the component summary scores range from 0 to 100, with higher scores indicating better health status.	Baseline to Week 20
Secondary	Area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t)		Baseline to Week 20
Secondary	Maximum observed concentration (Cmax)		Baseline to Week 20
Secondary	Terminal elimination half-life (T1/2)		Baseline to Week 20
Secondary	Time of occurrence of Cmax (Tmax)		Baseline to Week 20