<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/NCT04474847</url>
  </required_header>
  <id_info>
    <org_study_id>VCRC5528</org_study_id>
    <nct_id>NCT04474847</nct_id>
  </id_info>
  <brief_title>Abatacept for the Treatment of Giant Cell Arteritis</brief_title>
  <official_title>A Randomized Double-Blind, Placebo Controlled Trial of Abatacept (CTLA4-Ig) in Giant Cell Arteritis (ABAGART)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      This randomized, double-blind, placebo-controlled trial will seek to determine the efficacy&#xD;
      of abatacept in GCA. To examine this objective, 62 eligible patients who have newly diagnosed&#xD;
      or relapsing GCA within 8 weeks prior to screening will be randomized at a 1:1 ratio to&#xD;
      receive subcutaneous abatacept 125mg/week or placebo. Patients who achieve remission will&#xD;
      remain on their blinded assignment for 12 months at which time abatacept/placebo will be&#xD;
      stopped.&#xD;
&#xD;
      Patients who do not achieve remission by Month 3, who experience a relapse within the first&#xD;
      12 months will have the option of receiving open-label abatacept for a maximum of 12 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 15, 2021</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
  <phase>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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of participants in remission of those randomized to abatacept as compared to placebo.</measure>
    <time_frame>12 months</time_frame>
    <description>Remission is defined as the absence of clinical or imaging features of active disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of abatacept in GCA</measure>
    <time_frame>12 months</time_frame>
    <description>Safety of abatacept in patients with GCA as assessed by reported adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life in those treated with abatacept versus placebo: SF-36</measure>
    <time_frame>12 months</time_frame>
    <description>Health-related quality of life in those treated with abatacept versus placebo as assessed using the SF-36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life in those treated with abatacept versus placebo: PROMIS questionnaire</measure>
    <time_frame>12 months</time_frame>
    <description>Health-related quality of life in those treated with abatacept versus placebo as assessed using a PROMIS questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of glucocorticoid-free remission from Month 6 to Month 12</measure>
    <time_frame>6 months</time_frame>
    <description>Effect of abatacept on increasing duration of glucocorticoid-free periods for participants.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">78</enrollment>
  <condition>Giant Cell Arteritis</condition>
  <arm_group>
    <arm_group_label>Blinded Abatacept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive blinded abatacept 125 mg administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Blinded Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive blinded placebo. Placebo will be administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abatacept</intervention_name>
    <description>Participants randomized to abatacept will receive abatacept 125 mg administered by subcutaneous injection once a week. Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 3 will have the option of entering an open-label trial period whereby they would receive open-label abatacept for up to 12 months.</description>
    <arm_group_label>Blinded Abatacept</arm_group_label>
    <other_name>CTLA4-Ig</other_name>
    <other_name>Orencia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants randomized to placebo will receive a sterile placebo solution administered by subcutaneous injection once a week. Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 3 will have the option of entering an open-label trial period whereby they would receive open-label abatacept for up to 12 months.</description>
    <arm_group_label>Blinded Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA&#xD;
&#xD;
             A patient will be said to have GCA by meeting 3 of 5 of the following modified ACR&#xD;
             criteria for the classification of GCA in which 1 of the 3 must consist of criteria 4&#xD;
             or 5:&#xD;
&#xD;
               1. Age at disease onset ≥ 50 years.&#xD;
&#xD;
               2. New onset or new type of localized pain in the head.&#xD;
&#xD;
               3. ESR of &gt; 40 mm in the first hour by the Westergren method or CRP measurement&#xD;
                  above the laboratory normal limit.&#xD;
&#xD;
               4. Temporal artery abnormality (i.e., temporal artery tenderness to palpation or&#xD;
                  decreased pulsation, unrelated to arteriosclerosis of cervical arteries).&#xD;
&#xD;
               5. Temporal artery or large vessel biopsy showing vasculitis characterized by a&#xD;
                  predominance of mononuclear cell infiltration or granulomatous inflammation,&#xD;
                  usually with multinucleated giant cell or an abnormal temporal artery ultrasound&#xD;
                  showing features consistent with active giant cell arteritis (&quot;halo sign&quot;) or&#xD;
                  characteristic changes of large vessel stenosis or aneurysm by arteriography.&#xD;
&#xD;
          2. GCA with evidence of active disease (defined below) present within the past 8 weeks.&#xD;
&#xD;
          3. They must be willing and able to comply with treatment and follow-up procedures.&#xD;
&#xD;
          4. Both women and men who are of child-bearing potential must be willing to use an&#xD;
             effective means of birth control while receiving treatment through this study.&#xD;
             Effective contraception methods include abstinence, surgical sterilization of either&#xD;
             partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal&#xD;
             contraception.&#xD;
&#xD;
          5. They must be willing and able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of a recent acute infection defined as:&#xD;
&#xD;
               -  Any acute infection within 60 days prior to randomization that required&#xD;
                  hospitalization or treatment with parenteral antibiotics.&#xD;
&#xD;
               -  Any acute infection within 30 days prior to randomization that required oral&#xD;
                  antimicrobial or antiviral therapy.&#xD;
&#xD;
          2. Patients with history of chronic or recurrent bacterial infection (such as chronic&#xD;
             pyelonephritis, osteomyelitis, and bronchiectasis etc.).&#xD;
&#xD;
          3. Patients with a history of recurrent herpes zoster (more than 1 episode) or&#xD;
             disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or&#xD;
             ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolved more&#xD;
             than 60 days prior to screening.&#xD;
&#xD;
          4. Patients with a history of systemic fungal infections (such as histoplasmosis,&#xD;
             blastomycosis, or coccidiomycosis).&#xD;
&#xD;
          5. Patients with a history of primary immunodeficiency.&#xD;
&#xD;
          6. Patients at risk for tuberculosis (TB) defined as follows:&#xD;
&#xD;
               -  Current clinical, radiographic or laboratory evidence of active TB, even if&#xD;
                  currently being treated. Chest x-rays (posterior/anterior and lateral) obtained&#xD;
                  within the 6 months prior to screening and TB testing (IFN-gamma release assay or&#xD;
                  PPD) performed in the past month prior to screening will be accepted; however, a&#xD;
                  copy of the reports must be placed in the participant binder.&#xD;
&#xD;
               -  A history of active TB unless there is documentation that the patient had&#xD;
                  received prior anti-TB treatment that was appropriate in duration and type&#xD;
                  according to local health authority guidelines.&#xD;
&#xD;
               -  Patients with a positive TB screening test indicative of latent TB will not be&#xD;
                  eligible for the study unless they:&#xD;
&#xD;
                  i. Have no evidence of current TB based on chest x-ray performed during the&#xD;
                  screening period and by history and physical exam, and ii. They are currently&#xD;
                  being treated for latent TB or the site has documentation of successful prior&#xD;
                  treatment of latent TB. Treatment regimens should be dictated by local guidelines&#xD;
                  as long as the treatment dose and duration meet or exceed local health authority&#xD;
                  guidelines. If permitted by local guidelines regarding treatment with biologic&#xD;
                  medications, patients with latent TB may be randomized prior to completion of&#xD;
                  treatment as long as they have completed at least 4 weeks of treatment and they&#xD;
                  have no evidence of current TB on chest x-ray at screening.&#xD;
&#xD;
          7. Patients who are pregnant or who are nursing infants.&#xD;
&#xD;
          8. Inability to comply with study guidelines.&#xD;
&#xD;
          9. Cytopenia: platelet count &lt;80,000/mm3, total White Blood Count (WBC) &lt; 3,000/mm3 (3 x&#xD;
             109/L) absolute neutrophil &lt;1500/mm3, hematocrit &lt; 20%.&#xD;
&#xD;
         10. Renal insufficiency defined by a creatinine clearance of less than or equal to 20&#xD;
             ml/min.&#xD;
&#xD;
         11. AST or ALT &gt; 3 times above normal laboratory range.&#xD;
&#xD;
         12. Other severe, progressive, or uncontrolled disease that in the investigator's opinion&#xD;
             could prevent a patient from fulfilling the study requirements or that would increase&#xD;
             the risk of study participation.&#xD;
&#xD;
         13. Patients who have a present malignancy or previous malignancy within the last 5 years&#xD;
             prior to screening (except documented history of cured non-metastatic squamous or&#xD;
             basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening&#xD;
             procedure that is suspicious for malignancy, and in whom the possibility of malignancy&#xD;
             cannot be reasonably excluded following additional clinical, laboratory or other&#xD;
             diagnostic evaluations.&#xD;
&#xD;
         14. Receipt of an investigational agent or device within 30 days prior to enrollment.&#xD;
&#xD;
         15. A live vaccination within 3 months before randomization.&#xD;
&#xD;
         16. Patients on non-biologic immunosuppressants must discontinue these medications before&#xD;
             randomization (azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide,&#xD;
             hydroxychloroquine, cyclosporin, tacrolimus, or other conventional immunosuppressive&#xD;
             agent).&#xD;
&#xD;
         17. Patients who had received an alkylating agent such as cyclophosphamide must&#xD;
             discontinue these medications at least 8 weeks before randomization.&#xD;
&#xD;
         18. Patients who have been treated within 4 weeks of randomization with etanercept or&#xD;
             within 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.&#xD;
&#xD;
         19. Patients who have been treated within 8 weeks of randomization with anti-IL-6 agents&#xD;
             (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.&#xD;
&#xD;
         20. Patients who have been treated within 4 weeks of randomization with anakinra.&#xD;
&#xD;
         21. Patients who have received prior treatment with rituximab within the past 6 months&#xD;
             prior to randomization.&#xD;
&#xD;
         22. Patients who have received prior treatment with abatacept or CTLA4-Ig.&#xD;
&#xD;
         23. Patients who will require oral or IV glucocorticoid treatment during the trial for&#xD;
             conditions other than GCA.&#xD;
&#xD;
         24. Hypersensitivity to abatacept and/or its excipients.&#xD;
&#xD;
         25. Presence of any of the following disease processes:&#xD;
&#xD;
               -  Takayasu arteritis&#xD;
&#xD;
               -  Granulomatosis with polyangiitis&#xD;
&#xD;
               -  Microscopic polyangiitis&#xD;
&#xD;
               -  Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)&#xD;
&#xD;
               -  Polyarteritis nodosa&#xD;
&#xD;
               -  Cogan's syndrome&#xD;
&#xD;
               -  Behçet's disease&#xD;
&#xD;
               -  Sarcoidosis&#xD;
&#xD;
               -  Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics&#xD;
                  vasculitis&#xD;
&#xD;
               -  Cryoglobulinemic vasculitis&#xD;
&#xD;
               -  Systemic lupus erythematosus&#xD;
&#xD;
               -  Rheumatoid arthritis&#xD;
&#xD;
               -  Mixed connective tissue disease or any overlap autoimmune syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter A Merkel, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carol A Langford, MD, MHS</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeffrey P Krischer, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of South Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph's Healthcare</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vasculitis</keyword>
  <keyword>Arteritis</keyword>
  <keyword>Temporal Arteritis</keyword>
  <keyword>Abatacept</keyword>
  <keyword>CTLA4-Ig</keyword>
  <keyword>Autoimmune Diseases</keyword>
  <keyword>Immune System Diseases</keyword>
  <keyword>Immunosuppressive agent</keyword>
  <keyword>Prednisone</keyword>
  <keyword>Glucocorticoids</keyword>
  <keyword>Corticosteroids</keyword>
  <keyword>Treatment</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Anti Inflammatory Agents</keyword>
  <keyword>Antirheumatic Agents</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polymyalgia Rheumatica</mesh_term>
    <mesh_term>Giant Cell Arteritis</mesh_term>
    <mesh_term>Arteritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abatacept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04474847
org study id: VCRC5528
nct id: NCT04474847
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This randomized, double-blind, placebo-controlled trial will seek to determine the efficacy
      of abatacept in GCA. To examine this objective, 62 eligible patients who have newly diagnosed
      or relapsing GCA within 8 weeks prior to screening will be randomized at a 1:1 ratio to
      receive subcutaneous abatacept 125mg/week or placebo. Patients who achieve remission will
      remain on their blinded assignment for 12 months at which time abatacept/placebo will be
      stopped.

      Patients who do not achieve remission by Month 3, who experience a relapse within the first
      12 months will have the option of receiving open-label abatacept for a maximum of 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The proportion of participants in remission of those randomized to abatacept as compared to placebo.
time frame: 12 months
description: Remission is defined as the absence of clinical or imaging features of active disease
measure: Safety of abatacept in GCA
time frame: 12 months
description: Safety of abatacept in patients with GCA as assessed by reported adverse events.
measure: Health-related quality of life in those treated with abatacept versus placebo: SF-36
time frame: 12 months
description: Health-related quality of life in those treated with abatacept versus placebo as assessed using the SF-36
measure: Health-related quality of life in those treated with abatacept versus placebo: PROMIS questionnaire
time frame: 12 months
description: Health-related quality of life in those treated with abatacept versus placebo as assessed using a PROMIS questionnaire
measure: Duration of glucocorticoid-free remission from Month 6 to Month 12
time frame: 6 months
description: Effect of abatacept on increasing duration of glucocorticoid-free periods for participants.
arm group label: Blinded Abatacept
arm group type: Experimental
description: Participants will receive blinded abatacept 125 mg administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.
arm group label: Blinded Placebo
arm group type: Placebo Comparator
description: Participants will receive blinded placebo. Placebo will be administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission.
intervention type: Drug
intervention name: Abatacept
description: Participants randomized to abatacept will receive abatacept 125 mg administered by subcutaneous injection once a week. Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 3 will have the option of entering an open-label trial period whereby they would receive open-label abatacept for up to 12 months.
arm group label: Blinded Abatacept
other name: CTLA4-Ig
other name: Orencia
intervention type: Drug
intervention name: Placebo
description: Participants randomized to placebo will receive a sterile placebo solution administered by subcutaneous injection once a week. Participants randomized to either the abatacept or the placebo arm who experience a non-severe disease relapse, non-severe disease worsening, or who have not achieved remission by month 3 will have the option of entering an open-label trial period whereby they would receive open-label abatacept for up to 12 months.
arm group label: Blinded Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Peter A Merkel, MD, MPH
role: Principal Investigator
affiliation: University of Pennsylvania
last name: Carol A Langford, MD, MHS
role: Principal Investigator
affiliation: The Cleveland Clinic
last name: Jeffrey P Krischer, PhD
role: Principal Investigator
affiliation: University of South Florida
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Polymyalgia Rheumatica
mesh term: Giant Cell Arteritis
mesh term: Arteritis
mesh term: Abatacept
sharing ipd: No