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

Primary Purpose

Ankylosing Spondylitis

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK111
Placebo
Sponsored by
Akeso
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ankylosing Spondylitis focused on measuring AK111, Ankylosing Spondylitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The first affiliated hospital of Bengbu medical college
  • Peking university people's hospital
  • Peking University Shougang hospital
  • Peking University Third Hospital
  • Xuanwu hospital capital medical university
  • Guangdong provincial people's hospital
  • Nanfang Hospital
  • The first affiliated hospital of Zhengzhou University
  • Jiangsu Province Hospital
  • Nanjing Drum Tower hospital
  • Zhongda Hospital Southeast University
  • The First Affiliated Hospital of Nanchang University
  • The first Bethune hospital of Jilin university
  • Second hospital of Shanxi Medical university
  • The seventh affiliated hospital, Sun Yat-sen university

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

AK111 75mg

AK111 150mg

AK111 300mg

Placebo

Arm Description

AK111 75mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.

AK111 150mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.

AK111 300mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.

Placebo will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.
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.
pharmacodynamics(PD) parameters: Changes of Interleukin-17A (IL-17A) level in peripheral serum compared with baseline and its relationship with AK111 exposure.
Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).
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.
Area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t)
Maximum observed concentration (Cmax)
Terminal elimination half-life (T1/2)
Time of occurrence of Cmax (Tmax)

Full Information

First Posted
February 10, 2022
Last Updated
July 18, 2022
Sponsor
Akeso
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1. Study Identification

Unique Protocol Identification Number
NCT05467995
Brief Title
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2, 2021 (Actual)
Primary Completion Date
April 25, 2022 (Actual)
Study Completion Date
July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akeso

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ankylosing Spondylitis
Keywords
AK111, Ankylosing Spondylitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
125 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AK111 75mg
Arm Type
Experimental
Arm Description
AK111 75mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.
Arm Title
AK111 150mg
Arm Type
Experimental
Arm Description
AK111 150mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.
Arm Title
AK111 300mg
Arm Type
Experimental
Arm Description
AK111 300mg will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered by subcutaneous injection at Week 0, 1 and 4 , followed by dosing every 4 weeks until Week12.
Intervention Type
Biological
Intervention Name(s)
AK111
Intervention Description
AK111 administered subcutaneously at Week 0, 1, and 4, then every 4 weeks
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo administered subcutaneously at Week 0, 1, and 4, then every 4 weeks
Primary Outcome Measure Information:
Title
Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.
Description
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.
Time Frame
Week16
Title
Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.
Time Frame
Baseline to Week20
Title
Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.
Time Frame
Baseline to Week20
Secondary Outcome Measure Information:
Title
Percentage of subjects who achieve SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16.
Description
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.
Time Frame
Week 16
Title
Percentage of subjects who achieve ASAS20 response at each visit from baseline.
Description
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.
Time Frame
Baseline to Week 20
Title
Percentage of subjects who achieve ASAS40 at each visit from baseline.
Description
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.
Time Frame
Baseline to Week 20
Title
Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at each visit from baseline.
Description
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.
Time Frame
Baseline to Week 20
Title
pharmacodynamics(PD) parameters: Changes of Interleukin-17A (IL-17A) level in peripheral serum compared with baseline and its relationship with AK111 exposure.
Time Frame
Baseline to Week 20
Title
Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).
Time Frame
Baseline to Week 20
Title
Change from baseline on the 36-item Short-Form (SF-36) Health Survey at each visit from baseline.
Description
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.
Time Frame
Baseline to Week 20
Title
Area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t)
Time Frame
Baseline to Week 20
Title
Maximum observed concentration (Cmax)
Time Frame
Baseline to Week 20
Title
Terminal elimination half-life (T1/2)
Time Frame
Baseline to Week 20
Title
Time of occurrence of Cmax (Tmax)
Time Frame
Baseline to Week 20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
The first affiliated hospital of Bengbu medical college
City
Bengbu
State/Province
Anhui
Country
China
Facility Name
Peking university people's hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Peking University Shougang hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Peking University Third Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Xuanwu hospital capital medical university
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Guangdong provincial people's hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Nanfang Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
The first affiliated hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Nanjing Drum Tower hospital
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
Zhongda Hospital Southeast University
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
The First Affiliated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
Country
China
Facility Name
The first Bethune hospital of Jilin university
City
Changchun
State/Province
Jilin
Country
China
Facility Name
Second hospital of Shanxi Medical university
City
Taiyuan
State/Province
Shanxi
Country
China
Facility Name
The seventh affiliated hospital, Sun Yat-sen university
City
Shenzhen
State/Province
Shenzhen
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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

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