<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/NCT03239080</url>
  </required_header>
  <id_info>
    <org_study_id>RA-RANKL-2017</org_study_id>
    <nct_id>NCT03239080</nct_id>
  </id_info>
  <brief_title>Effect of Denosumab in Erosion Healing in RA</brief_title>
  <official_title>Effect of RANKL Inhibition on Healing of Bone Erosion in Rheumatoid Arthritis Using HR-pQCT</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese University of Hong Kong</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the effects of denosumab on erosion healing and change in physical function in RA&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled study, which aimed to evaluate the&#xD;
      effects of denosumab on erosion healing and change in physical function in rheumatoid&#xD;
      arthritis (RA) patients in low-disease activity or remission receiving synthetic DMARDs&#xD;
      (sDMARDs) treatment using High-resolution peripheral quantitative CT (HR-pQCT).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 19, 2017</start_date>
  <completion_date type="Actual">May 24, 2020</completion_date>
  <primary_completion_date type="Actual">May 24, 2020</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4</measure>
    <time_frame>12 months</time_frame>
    <description>1). A decrease in erosion volume of ≥ smallest detectable change (SDC) from baseline, and 2). The presence of &gt; SDC in osteosclerosis at the margin of erosion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4</measure>
    <time_frame>24 months</time_frame>
    <description>1). A decrease in erosion volume of ≥ smallest detectable change (SDC) from baseline, and 2). The presence of &gt; SDC in osteosclerosis at the margin of erosion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Erosion progression</measure>
    <time_frame>12 and 24 month</time_frame>
    <description>Changes in size of erosion (depth, width and volume) and marginal osteosclerosis (semi-quantitative and quantitative) using HR-pQCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic progression</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>Radiographic progression expressed by changes in van der Heijde-Sharp score on radiograph</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in various patient-reported outcomes</measure>
    <time_frame>12 and 24 month</time_frame>
    <description>Changes in physical function (HAQ) will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ</measure>
    <time_frame>24 month</time_frame>
    <description>Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ will be analysed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT</measure>
    <time_frame>12 and 24 month</time_frame>
    <description>Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Denosumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subcutaneous injections of placebo (0.9% Sodium Chloride solution) will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Denosumab</intervention_name>
    <description>Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).</description>
    <arm_group_label>Denosumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subcutaneous injections of placebo (0.9% Sodium Chloride solution) will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥18 years old&#xD;
&#xD;
          -  DAS28 ≤5.1&#xD;
&#xD;
          -  without severe deformity in MCP joints which would influence the longitudinal&#xD;
             assessment of HR-pQCT&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  RA functional status class IV (limited in ability to perform usual self-care,&#xD;
             vocational, and avocational activities)&#xD;
&#xD;
          -  treatment with any biologic DMARDs for RA treatment within 8 weeks before&#xD;
             randomisation&#xD;
&#xD;
          -  pregnancy or premenopausal women planning pregnancy&#xD;
&#xD;
          -  previous use of denosumab, zoledronic acid or teriparatide&#xD;
&#xD;
          -  Hyperparathyroidism&#xD;
&#xD;
          -  contraindications to denosumab&#xD;
&#xD;
          -  Bisphosphonate, biologic DMARDs and the use of oral glucocorticoid &gt;10 mg/day&#xD;
             (prednisolone equivalent)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lai Shan Tam, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Medicine and Therapeutics</name>
      <address>
        <city>Hong Kong</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>November 23, 2020</last_update_submitted>
  <last_update_submitted_qc>November 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Lai-Shan Tam</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>HR-pQCT</keyword>
  <keyword>erosion</keyword>
  <keyword>denosumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Denosumab</mesh_term>
  </intervention_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/NCT03239080
org study id: RA-RANKL-2017
nct id: NCT03239080
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
To evaluate the effects of denosumab on erosion healing and change in physical function in RA
      patients.
This is a randomized, double-blind, placebo-controlled study, which aimed to evaluate the
      effects of denosumab on erosion healing and change in physical function in rheumatoid
      arthritis (RA) patients in low-disease activity or remission receiving synthetic DMARDs
      (sDMARDs) treatment using High-resolution peripheral quantitative CT (HR-pQCT).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4
time frame: 12 months
description: 1). A decrease in erosion volume of ≥ smallest detectable change (SDC) from baseline, and 2). The presence of > SDC in osteosclerosis at the margin of erosion.
measure: The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4
time frame: 24 months
description: 1). A decrease in erosion volume of ≥ smallest detectable change (SDC) from baseline, and 2). The presence of > SDC in osteosclerosis at the margin of erosion.
measure: Erosion progression
time frame: 12 and 24 month
description: Changes in size of erosion (depth, width and volume) and marginal osteosclerosis (semi-quantitative and quantitative) using HR-pQCT
measure: Radiographic progression
time frame: 12 and 24 months
description: Radiographic progression expressed by changes in van der Heijde-Sharp score on radiograph
measure: Change in various patient-reported outcomes
time frame: 12 and 24 month
description: Changes in physical function (HAQ) will be measured
measure: Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ
time frame: 24 month
description: Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ will be analysed
measure: Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT
time frame: 12 and 24 month
description: Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT
arm group label: Denosumab
arm group type: Active Comparator
description: Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
arm group label: Placebo
arm group type: Placebo Comparator
description: Subcutaneous injections of placebo (0.9% Sodium Chloride solution) will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
intervention type: Drug
intervention name: Denosumab
description: Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
arm group label: Denosumab
intervention type: Other
intervention name: Placebo
description: Subcutaneous injections of placebo (0.9% Sodium Chloride solution) will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lai Shan Tam, MD
role: Principal Investigator
affiliation: Chinese University of Hong Kong
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese University of Hong Kong
investigator full name: Lai-Shan Tam
investigator title: Professor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Denosumab