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

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of AK111 in Subjects With Active Ankylosing Spondylitis

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical College
  • Beijing
    • Beijing, Beijing, China
      • Peking University Third Hospital
    • Beijing, Beijing, China
      • Peking University People's Hospital
    • Beijing, Beijing, China
      • Peking University Shougang Hospital
    • Beijing, Beijing, China
      • Xuanwu Hospital Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital
    • Guangzhou, Guangdong, China
      • Guangdong Provincial People's Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China
      • The First Bethune Hospital of Jilin University
  • Shanxi
    • Taiyuan, Shanxi, China
      • Second Hospital of Shanxi Medical University
  • Shenzhen
    • Shenzhen, Shenzhen, China
      • The Seventh Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK111 75mg; AK111 75mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.	Biological: AK111; AK111 administered subcutaneously at Week 0, 1, and 4, then every 4 weeks
Experimental: AK111 150mg; AK111 150mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.	Biological: AK111; AK111 administered subcutaneously at Week 0, 1, and 4, then every 4 weeks
Experimental: AK111 300mg; AK111 300mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.	Biological: AK111; AK111 administered subcutaneously at Week 0, 1, and 4, then every 4 weeks
Placebo Comparator: Placebo; Placebo will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.	Biological: Placebo; Placebo administered subcutaneously at Week 0, 1, and 4, then every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.		Baseline to Week20
Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.		Baseline to Week20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).		Baseline to Week 20
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
Area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t)		Baseline to Week 20
Maximum observed concentration (Cmax)		Baseline to Week 20
Terminal elimination half-life (T1/2)		Baseline to Week 20
Time of occurrence of Cmax (Tmax)		Baseline to Week 20

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Actual): April 25, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: February 10, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 21, 2022

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ankylosing Spondylitis; AK111
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Axial Spondyloarthritis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
• Other Study ID Numbers: AK111-202

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