<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04481139</url>
  </required_header>
  <id_info>
    <org_study_id>SHR0302-302</org_study_id>
    <nct_id>NCT04481139</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy and Safety of SHR0302 in Patients With Ankylosing Spondylitis</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled Adaptive Seamless Phase 2/3 Clinical Study to Evaluate the Efficacy and Safety of SHR0302 in Active Ankylosing Spondylitis Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to evaluate the efficacy and safety of different doses of JAK1 inhibitor&#xD;
      SHR0302 in subjects with active ankylosing spondylitis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">May 12, 2023</completion_date>
  <primary_completion_date type="Actual">November 15, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 12.</measure>
    <time_frame>Week 12</time_frame>
    <description>ASAS20 is defined as a &gt;= 20% improvement and an absolute improvement of &gt;= 1 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of &gt;= 20% and a net worsening of &gt;= 1 unit [on a scale of 0 to 10])</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 24.</measure>
    <time_frame>Week 24</time_frame>
    <description>ASAS20 is defined as a &gt;= 20% improvement and an absolute improvement of &gt;= 1 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of &gt;= 20% and a net worsening of &gt;= 1 unit [on a scale of 0 to 10]) at Week 24.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 40 response at Week 12 and Week 24.</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>ASAS40 is defined as a &gt;= 40% improvement and an absolute improvement of ≥ 2 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 5/6 response at Week 12 and Week 24.</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>ASAS5/6 is defined as an improvement of at least 20 % in at least five of these six domains (patient global, pain, function, inflammation, CRP, and spinal mobility).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>BASDAI is a commonly used measure to define disease activity levels in axSpA patients. It consists of 6 questions on a 0 through 10 numeric rating scale (NRS) (0 being no problem and 10 being the worst problem) pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain/swelling, Areas of localized tenderness, Morning stiffness duration, and Morning stiffness severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12 and Week 24.</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>The BASFI is a validated patient reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12 and Week 24.</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>The BASMI will be conducted at the visits specified to evaluate spinal mobility in a participan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Short-Form-36-Health Survey (SF-36) at Week 12 and Week 24.</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=no functioning, 100=highest level of functioning). Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 12 and Week 24.</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>The ASQoL is an 18-item axSpA-specific Quality of Life (QoL) PRO measure validated in the AS patient population. Concepts measured include activities of daily life, emotional functioning, pain, fatigue, and sleep problems. Each item on ASQoL is given a score of &quot;1&quot; or &quot;0,&quot; where a score of &quot;1&quot; is given when an item is affirmed indicating adverse QoL. Total scores can range from 0 (good QoL) to 18 (poor QoL).</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">504</enrollment>
  <condition>Ankylosing Spondylitis</condition>
  <arm_group>
    <arm_group_label>SHR0302 dose1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR0302 dose1 for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR0302 dose2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR0302 dose2 for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SHR0302 dose3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR0302 dose3 for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR0302</intervention_name>
    <description>SHR0302, oral, once daily</description>
    <arm_group_label>SHR0302 dose1</arm_group_label>
    <arm_group_label>SHR0302 dose2</arm_group_label>
    <arm_group_label>SHR0302 dose3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR0302 placebo</intervention_name>
    <description>SHR0302 placebo, oral, once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provide signed informed consent.&#xD;
&#xD;
          -  AS diagnosis consistent with the Modified New York Criteria for AS (1984);&#xD;
&#xD;
          -  Participant must have baseline disease activity as defined by having a Bath Ankylosing&#xD;
             Spondylitis Disease Activity Index (BASDAI) score &gt;= 4 and a Patient's Assessment of&#xD;
             Total Back Pain score &gt;= 4 based on a 0 - 10 Numeric Rating Scale (NRS) at the&#xD;
             Screening and Baseline Visits.&#xD;
&#xD;
          -  Participant has had an inadequate response to at least two Nonsteroidal&#xD;
             Anti-inflammatory Drugs (NSAIDs) over an at least 4-week period in total at maximum&#xD;
             recommended or tolerated doses, or participant has an intolerance to or&#xD;
             contraindication for NSAIDs as defined by the Investigator.&#xD;
&#xD;
          -  If subjects are taking permitted csDMARDs or low-dose corticosteroid orally at&#xD;
             baseline , the stable doses should have lasted for more than 4 weeks already.&#xD;
&#xD;
          -  BMI ≥18 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women or refuse to receive contraception during the study.&#xD;
&#xD;
          -  Lab abnormality within 4 weeks of randomization as follows: WBC count&#xD;
             &lt;3.0×10^9/L；neutrophil count&lt;1.5×10^9/L;hemoglobin level&lt;90.0 g/L ; platelet count&#xD;
             &lt;100×10^9/L; AST or ALT levels greater than the upper limit of normal; HBsAg or HCV or&#xD;
             HIV antibody positivity.&#xD;
&#xD;
          -  History of other autoimmune diseases ; history of cancer or infection including&#xD;
             tuberculosis and hepatitis; history of important cardiovascular events or thrombotic&#xD;
             diseases.&#xD;
&#xD;
          -  Previous treatment with JAK inhibitor or cytotoxic drugs; bDMARDs within 6 months of&#xD;
             randomization; other strong immunosuppressants within 6 months of randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Zhanguo Li</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>July 26, 2023</last_update_submitted>
  <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylitis</mesh_term>
    <mesh_term>Spondylarthritis</mesh_term>
    <mesh_term>Spondylitis, Ankylosing</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04481139
org study id: SHR0302-302
nct id: NCT04481139
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is to evaluate the efficacy and safety of different doses of JAK1 inhibitor
      SHR0302 in subjects with active ankylosing spondylitis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 12.
time frame: Week 12
description: ASAS20 is defined as a >= 20% improvement and an absolute improvement of >= 1 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 unit [on a scale of 0 to 10])
measure: Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 24.
time frame: Week 24
description: ASAS20 is defined as a >= 20% improvement and an absolute improvement of >= 1 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no deterioration in the remaining domain (where deterioration is defined as a worsening of >= 20% and a net worsening of >= 1 unit [on a scale of 0 to 10]) at Week 24.
measure: Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 40 response at Week 12 and Week 24.
time frame: Week 12 and Week 24
description: ASAS40 is defined as a >= 40% improvement and an absolute improvement of ≥ 2 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.
measure: Percentage of Participants with Assessment in Ankylosing Spondylitis (ASAS) 5/6 response at Week 12 and Week 24.
time frame: Week 12 and Week 24
description: ASAS5/6 is defined as an improvement of at least 20 % in at least five of these six domains (patient global, pain, function, inflammation, CRP, and spinal mobility).
measure: Change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
time frame: Week 12 and Week 24
description: BASDAI is a commonly used measure to define disease activity levels in axSpA patients. It consists of 6 questions on a 0 through 10 numeric rating scale (NRS) (0 being no problem and 10 being the worst problem) pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain/swelling, Areas of localized tenderness, Morning stiffness duration, and Morning stiffness severity.
measure: Change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12 and Week 24.
time frame: Week 12 and Week 24
description: The BASFI is a validated patient reported outcome (PRO) instrument for use in the AS patient population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to AS patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.
measure: Change from baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12 and Week 24.
time frame: Week 12 and Week 24
description: The BASMI will be conducted at the visits specified to evaluate spinal mobility in a participan.
measure: Change from baseline in Short-Form-36-Health Survey (SF-36) at Week 12 and Week 24.
time frame: Week 12 and Week 24
description: SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=no functioning, 100=highest level of functioning). Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
measure: Change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 12 and Week 24.
time frame: Week 12 and Week 24
description: The ASQoL is an 18-item axSpA-specific Quality of Life (QoL) PRO measure validated in the AS patient population. Concepts measured include activities of daily life, emotional functioning, pain, fatigue, and sleep problems. Each item on ASQoL is given a score of "1" or "0," where a score of "1" is given when an item is affirmed indicating adverse QoL. Total scores can range from 0 (good QoL) to 18 (poor QoL).
arm group label: SHR0302 dose1
arm group type: Experimental
description: SHR0302 dose1 for 24 weeks
arm group label: SHR0302 dose2
arm group type: Experimental
description: SHR0302 dose2 for 24 weeks
arm group label: SHR0302 dose3
arm group type: Experimental
description: SHR0302 dose3 for 24 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo for 12 weeks
intervention type: Drug
intervention name: SHR0302
description: SHR0302, oral, once daily
arm group label: SHR0302 dose1
arm group label: SHR0302 dose2
arm group label: SHR0302 dose3
intervention type: Drug
intervention name: SHR0302 placebo
description: SHR0302 placebo, oral, once daily
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Spondylitis
mesh term: Spondylarthritis
mesh term: Spondylitis, Ankylosing