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

March 5, 2024 updated by: Akeso

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
125

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of subjects who achieve Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response at Week 16.
Time Frame: Week16
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.
Time Frame: Baseline to Week20
Baseline to Week20
Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.
Time Frame: Baseline to Week20
Baseline to Week20

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of subjects who achieve SpondyloArthritis International Society 40% improvement (ASAS40) response at Week 16.
Time Frame: 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.
Time Frame: Baseline to Week 20
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.
Time Frame: Baseline to Week 20
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.
Time Frame: Baseline to Week 20
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.
Time Frame: Baseline to Week 20
Baseline to Week 20
Immunogenicity: Number and percentage of subjects with detectable anti-AK111 antibody (ADA).
Time Frame: Baseline to Week 20
Baseline to Week 20
Change from baseline on the 36-item Short-Form (SF-36) Health Survey at each visit from baseline.
Time Frame: Baseline to Week 20
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)
Time Frame: Baseline to Week 20
Baseline to Week 20
Maximum observed concentration (Cmax)
Time Frame: Baseline to Week 20
Baseline to Week 20
Terminal elimination half-life (T1/2)
Time Frame: Baseline to Week 20
Baseline to Week 20
Time of occurrence of Cmax (Tmax)
Time Frame: Baseline to Week 20
Baseline to Week 20

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Akeso

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 2, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 25, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 19, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 10, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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