<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/NCT01668004</url>
  </required_header>
  <id_info>
    <org_study_id>8259-012</org_study_id>
    <secondary_id>2012-002458-21</secondary_id>
    <nct_id>NCT01668004</nct_id>
  </id_info>
  <brief_title>The Incidence of Extra-Articular Manifestations in Participants With Ankylosing Spondylitis Treated With Golimumab (MK-8259-012)</brief_title>
  <acronym>GO-EASY</acronym>
  <official_title>Open-Label, Phase 4 Study, Investigating the Incidence of Extra-Articular Manifestations in Subjects With Ankylosing Spondylitis Treated With Golimumab; Protocol No. MK-8259-012</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to determine the difference in the annual incidence rate of&#xD;
      uveitis attacks in participants with ankylosing spondylitis (AS) before start initial&#xD;
      anti-TNF therapy and after treatment with golimumab (GLM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, history-controlled, multi-site study of GLM in participants with AS.&#xD;
      For evaluation of the primary study outcome measure, participants will serve as their own&#xD;
      control. The period before start of treatment with an anti-tumor necrosis factor (TNF) agent&#xD;
      will serve as historical control for the incidence of extra-articular manifestations, with a&#xD;
      review of the medical records done for the previous 1-year period.&#xD;
&#xD;
      Each participant will participate in the study for approximately 12 months from the time the&#xD;
      participant signs the Informed Consent Form through the final contact. After screening, two&#xD;
      to four weeks before study start, each participant will be receiving study treatment for&#xD;
      approximately 12 months, depending on the response to GLM after 3 months. All participants&#xD;
      will be followed for a minimum of 12 months, irrespective of the duration of GLM treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 3, 2012</start_date>
  <completion_date type="Actual">April 30, 2015</completion_date>
  <primary_completion_date type="Actual">April 30, 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurence Rate of Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</measure>
    <time_frame>Twelve Months Prior to Enrollment to Study Month 12</time_frame>
    <description>Uveitis is an extra-articular manifestation of ankylosing spondylitis (AS) involving inflammation of the eye. The occurrence rate (assessed as present/absent) of uveitis attacks was determined over two 1-year long periods regardless of whether the event started during the assessed year: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Annual Incidence Rate of New Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</measure>
    <time_frame>Twelve Months Prior to Enrollment to Study Month 12</time_frame>
    <description>Uveitis is an extra-articular manifestation of AS involving inflammation of the eye. The annual incidence rate of new uveitis attacks was determined over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. All participants were counted as contributing a full year of GLM exposure even if discontinuing early. Due to ongoing uveitis cases at time of period entry, participants did not have the same risk of new events during the one year periods. Participants with ongoing uveitis at start of GLM who had the adverse event for the entire treatment period were counted as having the 'new attack' before and no &quot;new attack&quot; after GLM treatment start.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annual Incidence Rate of New-Onset or Flares of Inflammatory Bowel Disease (IBD) and Psoriasis in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</measure>
    <time_frame>Twelve Months Prior to Enrollment to Study Month 12</time_frame>
    <description>IBD (Crohn's disease or ulcerative colitis) and psoriaris are extra-articular manifestations of AS involving the intestinal tract and skin, respectively. The annual incidence rates of new-onset or flares of IBD and psoriasis were to be determined separately (i.e., for each condition) over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) Responders Following Treatment With GLM</measure>
    <time_frame>Baseline (BL), Study Month 3</time_frame>
    <description>The percentage of participants with a BASDAI 50 response (defined as a 50% improvement or as an absolute improvement of 2 points in their BASDAI physical function score) at three months was determined. The BASDAI consists of total of six visual analog scales (VAS): five VAS (0 to 10 cm; increasing severity) measuring severity of fatigue, spinal pain, peripheral joint pain or swelling, localized tenderness, and severity of morning stiffness and one VAS (0 to 10 cm; increasing duration up to 2 hours) measuring duration of morning stiffness. The morning stiffness scores are averaged and summed with the scores for the remaining four items resulting in a composite score (0-50); the final BASDAI score (0-10) is derived by dividing by 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM</measure>
    <time_frame>BL, Study Month 3</time_frame>
    <description>The percentage of participants with ASDAS clinically important improvement (ASDAS-CII; ≥ 1.1 units) and major improvement (ASDAS-MI; ≥ 2.0 units) at 3 months were determined. The ASDAS incorporates three items from the BASDAI (spinal pain, duration of morning stiffness, and peripheral joint pain or swelling) each assessed on a VAS (0 to 10 cm; increasing severity) as well as patient global assessment of disease activity (VAS; 0 to 10 cm; increasing severity) and a laboratory measure of inflammation (CRP level [mg/L] or ESR [mm/hr]). ASDAS was calculated using the formula: 0.12*Spinal Pain + 0.06*Duration of Morning Stiffness + 0.11*Patient Global + 0.07*Peripheral Pain/Swelling + 0.58*ln(CRP (mg/L) +1). A decrease in ASDAS at 3 months relative to BL signifies an improvement in physical function; ASDAS-MI (≥ 2.0 units decrease from BL) signifies a comparatively greater improvement in physical function than ASDAS-CII (≥ 1.1 units decrease from BL).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">101</enrollment>
  <condition>Ankylosing Spondylitis</condition>
  <arm_group>
    <arm_group_label>GLM 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Golimumab</intervention_name>
    <description>GLM 50 mg subcutaneously once monthly.</description>
    <arm_group_label>GLM 50 mg</arm_group_label>
    <other_name>Simponi®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  May not have been treated with GLM prior to study enrollment&#xD;
&#xD;
          -  Must be able to provide retrospective data concerning extra-articular manifestations&#xD;
             and episodes with a recall period of at least 12 months prior to anti-TNF use&#xD;
&#xD;
          -  Must have definite AS according to the modified New York criteria in the Netherlands&#xD;
&#xD;
          -  Must be candidate for treatment with anti-TNF agent according to the Assessment of&#xD;
             SpondyloArthritis International Society (ASAS) consensus&#xD;
&#xD;
          -  Must be able to adhere to dose and visit schedules&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any exclusion criteria stated in the Summary of Product Characteristics for golimumab&#xD;
&#xD;
          -  Use of any investigational biological or chemical agents within 30 days or 2&#xD;
             half-lives (whichever is longest) of screening&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Netherlands</country>
  </removed_countries>
  <reference>
    <citation>van Bentum RE, Heslinga SC, Nurmohamed MT, Gerards AH, Griep EN, Koehorst CBJM, Kok MR, Schilder AM, Verhoef M, van der Horst-Bruinsma IE. Reduced Occurrence Rate of Acute Anterior Uveitis in Ankylosing Spondylitis Treated with Golimumab - The GO-EASY Study. J Rheumatol. 2019 Feb;46(2):153-159. doi: 10.3899/jrheum.180312. Epub 2018 Nov 1.</citation>
    <PMID>30385705</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>August 1, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>April 15, 2016</results_first_submitted>
  <results_first_submitted_qc>June 20, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 3, 2016</results_first_posted>
  <last_update_submitted>January 16, 2019</last_update_submitted>
  <last_update_submitted_qc>January 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2019</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Golimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 104 participants were screened; 3 participants were screen failures who did not enroll.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>GLM 50 mg</title>
          <description>Golimumab (GLM) given subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="101"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="101"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with treatment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>GLM 50 mg</title>
          <description>GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="101"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.4" spread="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time since diagnosis</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.8" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at onset of disease</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.1" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="175.82" spread="9.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82.63" spread="18.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Abdominal circumference</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="95.5" spread="15.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Occurence Rate of Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</title>
        <description>Uveitis is an extra-articular manifestation of ankylosing spondylitis (AS) involving inflammation of the eye. The occurrence rate (assessed as present/absent) of uveitis attacks was determined over two 1-year long periods regardless of whether the event started during the assessed year: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.</description>
        <time_frame>Twelve Months Prior to Enrollment to Study Month 12</time_frame>
        <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (occurence of uveitis).</population>
        <group_list>
          <group group_id="O1">
            <title>Before Initial Anti-TNF/GLM Treatment</title>
            <description>Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).</description>
          </group>
          <group group_id="O2">
            <title>After GLM Treatment Start</title>
            <description>GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Occurence Rate of Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</title>
          <description>Uveitis is an extra-articular manifestation of ankylosing spondylitis (AS) involving inflammation of the eye. The occurrence rate (assessed as present/absent) of uveitis attacks was determined over two 1-year long periods regardless of whether the event started during the assessed year: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.</description>
          <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (occurence of uveitis).</population>
          <units>Ratio</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="93"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08"/>
                    <measurement group_id="O2" value="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Treatment comparison of uveitis occurrence rate assessed 1 year before initial anti-TNF/GLM treatment and 1 year after start of GLM treatment. Number of subjects included in analysis: N=93.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>1.0000</p_value>
            <method>McNemar</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Annual Incidence Rate of New Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</title>
        <description>Uveitis is an extra-articular manifestation of AS involving inflammation of the eye. The annual incidence rate of new uveitis attacks was determined over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. All participants were counted as contributing a full year of GLM exposure even if discontinuing early. Due to ongoing uveitis cases at time of period entry, participants did not have the same risk of new events during the one year periods. Participants with ongoing uveitis at start of GLM who had the adverse event for the entire treatment period were counted as having the 'new attack' before and no &quot;new attack&quot; after GLM treatment start.</description>
        <time_frame>Twelve Months Prior to Enrollment to Study Month 12</time_frame>
        <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (incidence of uveitis). One participant for whom the timing of uveitis events could not be determined was excluded from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Before Initial Anti-TNF/GLM Treatment</title>
            <description>Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).</description>
          </group>
          <group group_id="O2">
            <title>After GLM Treatment Start</title>
            <description>GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Incidence Rate of New Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</title>
          <description>Uveitis is an extra-articular manifestation of AS involving inflammation of the eye. The annual incidence rate of new uveitis attacks was determined over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. All participants were counted as contributing a full year of GLM exposure even if discontinuing early. Due to ongoing uveitis cases at time of period entry, participants did not have the same risk of new events during the one year periods. Participants with ongoing uveitis at start of GLM who had the adverse event for the entire treatment period were counted as having the 'new attack' before and no &quot;new attack&quot; after GLM treatment start.</description>
          <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (incidence of uveitis). One participant for whom the timing of uveitis events could not be determined was excluded from the analysis.</population>
          <units>Events per 100 participant years</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="92"/>
                <count group_id="O2" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8"/>
                    <measurement group_id="O2" value="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Treatment difference (expressed as ratio) in uveitis incidence rate assessed 1 year before initial anti-TNF/GLM treatment and 1 year after start of GLM treatment. Number of subjects included in analysis: N=92.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Generalized estimating equation</method>
            <param_type>Treatment Ratio</param_type>
            <param_value>4.50</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.86</ci_lower_limit>
            <ci_upper_limit>5.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annual Incidence Rate of New-Onset or Flares of Inflammatory Bowel Disease (IBD) and Psoriasis in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</title>
        <description>IBD (Crohn's disease or ulcerative colitis) and psoriaris are extra-articular manifestations of AS involving the intestinal tract and skin, respectively. The annual incidence rates of new-onset or flares of IBD and psoriasis were to be determined separately (i.e., for each condition) over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.</description>
        <time_frame>Twelve Months Prior to Enrollment to Study Month 12</time_frame>
        <population>The incidence rates for new onset or flares of IBD and psoriasis could not be evaluated due to limitations of the data collected; occurrence of flares was not collected (specifically, history of IBD and/or psoriasis could not be distinguished from flares of IBD and/or psoriasis) and, therefore, results could not be determined.</population>
        <group_list>
          <group group_id="O1">
            <title>Before Initial Anti-TNF/GLM Treatment</title>
            <description>Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).</description>
          </group>
          <group group_id="O2">
            <title>After GLM Treatment Start</title>
            <description>GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Annual Incidence Rate of New-Onset or Flares of Inflammatory Bowel Disease (IBD) and Psoriasis in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment</title>
          <description>IBD (Crohn's disease or ulcerative colitis) and psoriaris are extra-articular manifestations of AS involving the intestinal tract and skin, respectively. The annual incidence rates of new-onset or flares of IBD and psoriasis were to be determined separately (i.e., for each condition) over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.</description>
          <population>The incidence rates for new onset or flares of IBD and psoriasis could not be evaluated due to limitations of the data collected; occurrence of flares was not collected (specifically, history of IBD and/or psoriasis could not be distinguished from flares of IBD and/or psoriasis) and, therefore, results could not be determined.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) Responders Following Treatment With GLM</title>
        <description>The percentage of participants with a BASDAI 50 response (defined as a 50% improvement or as an absolute improvement of 2 points in their BASDAI physical function score) at three months was determined. The BASDAI consists of total of six visual analog scales (VAS): five VAS (0 to 10 cm; increasing severity) measuring severity of fatigue, spinal pain, peripheral joint pain or swelling, localized tenderness, and severity of morning stiffness and one VAS (0 to 10 cm; increasing duration up to 2 hours) measuring duration of morning stiffness. The morning stiffness scores are averaged and summed with the scores for the remaining four items resulting in a composite score (0-50); the final BASDAI score (0-10) is derived by dividing by 5.</description>
        <time_frame>Baseline (BL), Study Month 3</time_frame>
        <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (BASDAI 50).</population>
        <group_list>
          <group group_id="O1">
            <title>GLM 50 mg</title>
            <description>GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) Responders Following Treatment With GLM</title>
          <description>The percentage of participants with a BASDAI 50 response (defined as a 50% improvement or as an absolute improvement of 2 points in their BASDAI physical function score) at three months was determined. The BASDAI consists of total of six visual analog scales (VAS): five VAS (0 to 10 cm; increasing severity) measuring severity of fatigue, spinal pain, peripheral joint pain or swelling, localized tenderness, and severity of morning stiffness and one VAS (0 to 10 cm; increasing duration up to 2 hours) measuring duration of morning stiffness. The morning stiffness scores are averaged and summed with the scores for the remaining four items resulting in a composite score (0-50); the final BASDAI score (0-10) is derived by dividing by 5.</description>
          <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (BASDAI 50).</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="88"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM</title>
        <description>The percentage of participants with ASDAS clinically important improvement (ASDAS-CII; ≥ 1.1 units) and major improvement (ASDAS-MI; ≥ 2.0 units) at 3 months were determined. The ASDAS incorporates three items from the BASDAI (spinal pain, duration of morning stiffness, and peripheral joint pain or swelling) each assessed on a VAS (0 to 10 cm; increasing severity) as well as patient global assessment of disease activity (VAS; 0 to 10 cm; increasing severity) and a laboratory measure of inflammation (CRP level [mg/L] or ESR [mm/hr]). ASDAS was calculated using the formula: 0.12*Spinal Pain + 0.06*Duration of Morning Stiffness + 0.11*Patient Global + 0.07*Peripheral Pain/Swelling + 0.58*ln(CRP (mg/L) +1). A decrease in ASDAS at 3 months relative to BL signifies an improvement in physical function; ASDAS-MI (≥ 2.0 units decrease from BL) signifies a comparatively greater improvement in physical function than ASDAS-CII (≥ 1.1 units decrease from BL).</description>
        <time_frame>BL, Study Month 3</time_frame>
        <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (ASDAS).</population>
        <group_list>
          <group group_id="O1">
            <title>GLM 50 mg</title>
            <description>GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM</title>
          <description>The percentage of participants with ASDAS clinically important improvement (ASDAS-CII; ≥ 1.1 units) and major improvement (ASDAS-MI; ≥ 2.0 units) at 3 months were determined. The ASDAS incorporates three items from the BASDAI (spinal pain, duration of morning stiffness, and peripheral joint pain or swelling) each assessed on a VAS (0 to 10 cm; increasing severity) as well as patient global assessment of disease activity (VAS; 0 to 10 cm; increasing severity) and a laboratory measure of inflammation (CRP level [mg/L] or ESR [mm/hr]). ASDAS was calculated using the formula: 0.12*Spinal Pain + 0.06*Duration of Morning Stiffness + 0.11*Patient Global + 0.07*Peripheral Pain/Swelling + 0.58*ln(CRP (mg/L) +1). A decrease in ASDAS at 3 months relative to BL signifies an improvement in physical function; ASDAS-MI (≥ 2.0 units decrease from BL) signifies a comparatively greater improvement in physical function than ASDAS-CII (≥ 1.1 units decrease from BL).</description>
          <population>All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (ASDAS).</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ASDAS-CII (≥ 1.1 units)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ASDAS-MI (≥ 2.0 units)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to one year</time_frame>
      <desc>All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.</desc>
      <group_list>
        <group group_id="E1">
          <title>GLM 50 mg</title>
          <description>GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Coronary Syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
              <event>
                <sub_title>Cardiac Failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colitis Ulcerative</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
              <event>
                <sub_title>Large Intestinal Ulcer Haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Prostate Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Fistula Repair</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypovolaemic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="11" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="19" subjects_affected="13" subjects_at_risk="101"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation with regard to proprietary information, accuracy of information, and regulatory compliance.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01668004
org study id: 8259-012
secondary id: 2012-002458-21
nct id: NCT01668004
lead sponsor: 
has dmc: No
The objective of this study is to determine the difference in the annual incidence rate of
      uveitis attacks in participants with ankylosing spondylitis (AS) before start initial
      anti-TNF therapy and after treatment with golimumab (GLM).
This is an open-label, history-controlled, multi-site study of GLM in participants with AS.
      For evaluation of the primary study outcome measure, participants will serve as their own
      control. The period before start of treatment with an anti-tumor necrosis factor (TNF) agent
      will serve as historical control for the incidence of extra-articular manifestations, with a
      review of the medical records done for the previous 1-year period.

      Each participant will participate in the study for approximately 12 months from the time the
      participant signs the Informed Consent Form through the final contact. After screening, two
      to four weeks before study start, each participant will be receiving study treatment for
      approximately 12 months, depending on the response to GLM after 3 months. All participants
      will be followed for a minimum of 12 months, irrespective of the duration of GLM treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurence Rate of Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment
time frame: Twelve Months Prior to Enrollment to Study Month 12
description: Uveitis is an extra-articular manifestation of ankylosing spondylitis (AS) involving inflammation of the eye. The occurrence rate (assessed as present/absent) of uveitis attacks was determined over two 1-year long periods regardless of whether the event started during the assessed year: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.
measure: Annual Incidence Rate of New Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment
time frame: Twelve Months Prior to Enrollment to Study Month 12
description: Uveitis is an extra-articular manifestation of AS involving inflammation of the eye. The annual incidence rate of new uveitis attacks was determined over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. All participants were counted as contributing a full year of GLM exposure even if discontinuing early. Due to ongoing uveitis cases at time of period entry, participants did not have the same risk of new events during the one year periods. Participants with ongoing uveitis at start of GLM who had the adverse event for the entire treatment period were counted as having the 'new attack' before and no "new attack" after GLM treatment start.
measure: Annual Incidence Rate of New-Onset or Flares of Inflammatory Bowel Disease (IBD) and Psoriasis in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment
time frame: Twelve Months Prior to Enrollment to Study Month 12
description: IBD (Crohn's disease or ulcerative colitis) and psoriaris are extra-articular manifestations of AS involving the intestinal tract and skin, respectively. The annual incidence rates of new-onset or flares of IBD and psoriasis were to be determined separately (i.e., for each condition) over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.
measure: Percentage of Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) Responders Following Treatment With GLM
time frame: Baseline (BL), Study Month 3
description: The percentage of participants with a BASDAI 50 response (defined as a 50% improvement or as an absolute improvement of 2 points in their BASDAI physical function score) at three months was determined. The BASDAI consists of total of six visual analog scales (VAS): five VAS (0 to 10 cm; increasing severity) measuring severity of fatigue, spinal pain, peripheral joint pain or swelling, localized tenderness, and severity of morning stiffness and one VAS (0 to 10 cm; increasing duration up to 2 hours) measuring duration of morning stiffness. The morning stiffness scores are averaged and summed with the scores for the remaining four items resulting in a composite score (0-50); the final BASDAI score (0-10) is derived by dividing by 5.
measure: Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM
time frame: BL, Study Month 3
description: The percentage of participants with ASDAS clinically important improvement (ASDAS-CII; ≥ 1.1 units) and major improvement (ASDAS-MI; ≥ 2.0 units) at 3 months were determined. The ASDAS incorporates three items from the BASDAI (spinal pain, duration of morning stiffness, and peripheral joint pain or swelling) each assessed on a VAS (0 to 10 cm; increasing severity) as well as patient global assessment of disease activity (VAS; 0 to 10 cm; increasing severity) and a laboratory measure of inflammation (CRP level [mg/L] or ESR [mm/hr]). ASDAS was calculated using the formula: 0.12*Spinal Pain + 0.06*Duration of Morning Stiffness + 0.11*Patient Global + 0.07*Peripheral Pain/Swelling + 0.58*ln(CRP (mg/L) +1). A decrease in ASDAS at 3 months relative to BL signifies an improvement in physical function; ASDAS-MI (≥ 2.0 units decrease from BL) signifies a comparatively greater improvement in physical function than ASDAS-CII (≥ 1.1 units decrease from BL).
arm group label: GLM 50 mg
arm group type: Experimental
description: GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months
intervention type: Biological
intervention name: Golimumab
description: GLM 50 mg subcutaneously once monthly.
arm group label: GLM 50 mg
other name: Simponi®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Netherlands
citation: van Bentum RE, Heslinga SC, Nurmohamed MT, Gerards AH, Griep EN, Koehorst CBJM, Kok MR, Schilder AM, Verhoef M, van der Horst-Bruinsma IE. Reduced Occurrence Rate of Acute Anterior Uveitis in Ankylosing Spondylitis Treated with Golimumab - The GO-EASY Study. J Rheumatol. 2019 Feb;46(2):153-159. doi: 10.3899/jrheum.180312. Epub 2018 Nov 1.
PMID: 30385705
responsible party type: Sponsor
mesh term: Spondylitis
mesh term: Spondylarthritis
mesh term: Spondylitis, Ankylosing
mesh term: Golimumab
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 