<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/NCT03303989</url>
  </required_header>
  <id_info>
    <org_study_id>300000591</org_study_id>
    <nct_id>NCT03303989</nct_id>
  </id_info>
  <brief_title>REduCing Immunogenicity to PegloticasE (RECIPE) Study</brief_title>
  <acronym>RECIPE</acronym>
  <official_title>REduCing Immunogenicity to PegloticasE (RECIPE) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Alabama at Birmingham</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pegloticase treatment for chronic refractory gout is limited by immunogenicity. The&#xD;
      investigators propose the REduCing Immunogenicity to PegloticasE (RECIPE) trial to begin to&#xD;
      investigate the question of whether a short course of immune modulating therapy with&#xD;
      mycophenolate mofetil can significantly and safely attenuate immunogenicity to pegloticase&#xD;
      and ensure patients afflicted with chronic refractory gout have better treatment outcomes and&#xD;
      improved quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pegloticase is highly efficacious therapy for chronic refractory gout patients (n = &gt; 400K in&#xD;
      the US alone). It decreases serum urate (sUA) levels to often undetectable levels and reduces&#xD;
      tophi burden. However, its long-term real world effectiveness is severely limited due to its&#xD;
      immunogenicity caused by anti-pegloticase antibody formation. REducing Immunogenicity to&#xD;
      PEgloticase (RECIPE) is a Phase II, double-blind, placebo controlled, proof-of-concept trial&#xD;
      in 32 subjects initiating pegloticase for treatment of chronic refractory gout. RECIPE will&#xD;
      investigate the preliminary efficacy and safety of using immune modulating therapy with&#xD;
      mycophenolate mofetil (MMF) to prevent immunogenicity conferred by pegloticase. Subjects will&#xD;
      be randomized 3:1 to receive MMF vs. placebo in addition to everyone receiving pegloticase.&#xD;
      The co-primary aims of the RECIPE trial are to 1) determine if a 12 week course of immune&#xD;
      modulating therapy with daily MMF can safely and significantly attenuate immunogenicity to&#xD;
      pegloticase as determined by the proportion of participants achieving and maintaining an sUA&#xD;
      less than or equal to 6 mg/dL through 12 weeks, compared to concurrent controls, and 2) to&#xD;
      assess the incidence and types of adverse events and infusion reaction. After 12 weeks of&#xD;
      co-administration, all participants will continue on pegloticase for an additional 12 weeks&#xD;
      without combination MMF immune modulating therapy to evaluate the longer term benefits&#xD;
      (durability) and safety of this approach. The secondary aims are to: 1) Determine the 6 month&#xD;
      durability of immune modulation after discontinuation of the short course of MMF by: a)&#xD;
      assessing the absolute change in sUA from baseline to Week 24, and Week 12 to Week 24 and b)&#xD;
      determining the proportion of participants with sUA ≤ 6 mg/dL through 24 weeks, and Week 12&#xD;
      to Week 24; 2) Identify and characterize the pegloticase immune response by immunoglobulin&#xD;
      isotypes (IgG and IgM), specificities, and antibody titer; and 3) Examine patient reported&#xD;
      outcomes (PROs) using the NIH supported Patient Reported Outcomes Measurement Information&#xD;
      System (PROMIS) and Gout Impact Scale (GIS) instruments. The University of Alabama at&#xD;
      Birmingham (UAB) and the University of Michigan (UM), two large academic gout and immunology&#xD;
      research centers, which in aggregate see nearly 10,000 gout patients annually, will serve as&#xD;
      the two lead study sites and are very well-positioned to address the clinical and immunologic&#xD;
      questions posed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 14, 2018</start_date>
  <completion_date type="Actual">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">April 27, 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>
    <intervention_model_description>Phase II, double blind, placebo controlled multisite proof-of-concept trial in subjects initiating pegloticase for treatment of chronic gout</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Gout Chronic</condition>
  <arm_group>
    <arm_group_label>pegloticase + MMF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>pegloticase + placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to this arm will receive pegloticase + placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegloticase 8 MG/ML [Krystexxa]</intervention_name>
    <description>Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
    <arm_group_label>pegloticase + MMF</arm_group_label>
    <other_name>Krystexxa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MMF</intervention_name>
    <description>Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
    <arm_group_label>pegloticase + MMF</arm_group_label>
    <other_name>Cell Cept</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
    <arm_group_label>pegloticase + placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegloticase 8 MG/ML [Krystexxa]</intervention_name>
    <description>Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
    <arm_group_label>pegloticase + placebo</arm_group_label>
    <other_name>Krystexxa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women &gt; 18 years of age&#xD;
&#xD;
          -  Diagnosed with chronic refractory gout*&#xD;
&#xD;
               -  Defined as: Persons whose signs and symptoms are inadequately controlled with&#xD;
                  urate lowering therapy (e.g. xanthine oxidase inhibitors or uricosuric agents) at&#xD;
                  a medically appropriate dose or for whom these drugs are contraindicated.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious acute bacterial infection (2 weeks prior to Visit 1), unless treated and&#xD;
             completely resolved with antibiotics&#xD;
&#xD;
          -  Severe chronic or recurrent bacterial infections (such as recurrent pneumonia, chronic&#xD;
             bronchiectasis)&#xD;
&#xD;
          -  Current immunocompromised condition, including current or chronic treatment with&#xD;
             immunosuppressive agents&#xD;
&#xD;
          -  Subjects at risk for tuberculosis. Specifically, subjects with: i) current clinical,&#xD;
             radiographic or laboratory evidence of active or latent TB; ii) a history of active TB&#xD;
             within the last 3 years even if it was treated; iii) a history of active TB greater&#xD;
             than 3 years ago unless there is documentation that the prior anti-TB treatment was&#xD;
             appropriate in duration and type&#xD;
&#xD;
          -  Known Hepatitis B surface antigen-positive or Hepatitis B DNA positive subjects&#xD;
&#xD;
          -  Known Hepatitis C RNA-positive subjects&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV) infection&#xD;
&#xD;
          -  G6PD deficiency (tested at Screening Visit 1)&#xD;
&#xD;
          -  Severe chronic renal impairment (glomerular filtration rate [GFR] &lt;25 mL/min/1.73 m2)&#xD;
             or currently on dialysis&#xD;
&#xD;
          -  Subjects having any transplant surgery requiring maintenance immunosuppressive therapy&#xD;
&#xD;
          -  Non-compensated congestive heart failure, uncontrolled arrhythmia, treatment for acute&#xD;
             coronary syndrome (myocardial infarction or unstable angina), or hospitalization for&#xD;
             congestive heart failure within 3 months of screening or uncontrolled blood pressure&#xD;
             (&gt;160/100 mm Hg) at baseline (Screening Visit 1 and Week 0/Baseline visits)&#xD;
&#xD;
          -  Participants who are pregnant, planning to become pregnant, breastfeeding, or not on&#xD;
             an effective form of birth control (defined in Study Protocol section 7.1)&#xD;
&#xD;
          -  Prior treatment with pegloticase, another recombinant uricase, or concomitant therapy&#xD;
             with a polyethylene glycol (PEG)-conjugated drug&#xD;
&#xD;
          -  Known allergy to pegylated products or history of anaphylactic reaction to a&#xD;
             recombinant protein or porcine product&#xD;
&#xD;
          -  Subjects in whom MMF treatment is contraindicated or considered inappropriate&#xD;
&#xD;
          -  Recipient of an investigational drug within 4 weeks prior to study drug administration&#xD;
             or plans to take an investigational agent during the study&#xD;
&#xD;
          -  Current liver disease as determined by alanine transaminase ALT or aspartate&#xD;
             transaminase (AST) levels &gt;3 times upper limit of normal&#xD;
&#xD;
          -  Currently receiving treatment for ongoing cancer, excluding non-melanoma skin cancer&#xD;
&#xD;
          -  History of malignancy within 5 years other than skin cancer or in situ carcinoma of&#xD;
             cervix&#xD;
&#xD;
          -  Uncontrolled hyperglycemia with a plasma glucose value &gt;240 mg/dL at screening&#xD;
&#xD;
          -  Diagnosed osteomyelitis&#xD;
&#xD;
          -  Individuals with hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) deficiency&#xD;
             such as Lesch-Nyhan and Kelley-Seegmiller syndrome&#xD;
&#xD;
          -  Not good candidate for the study based on opinion of the Investigator (e.g., cognitive&#xD;
             impairment) that might create undue risk to the participant or interfere with the&#xD;
             participant's ability to comply with the protocol requirements, or to complete the&#xD;
             study&#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>Kenneth G Saag, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <results_first_submitted>June 29, 2021</results_first_submitted>
  <results_first_submitted_qc>October 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 10, 2021</results_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Kenneth Saag, MD, MSc</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT03303989/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Pegloticase + MMF</title>
          <description>Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
        </group>
        <group group_id="P2">
          <title>Pegloticase + Placebo</title>
          <description>Participants randomized to this arm will receive pegloticase + placebo&#xD;
Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three 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="24"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>35 participants were randomized. Three participants withdrew after randomization, but prior to first pegloticase infusion. Baseline characteristics are of the 32 participants (22 in MMF+Peg, 10 in PBO+Peg)</population>
      <group_list>
        <group group_id="B1">
          <title>Pegloticase + MMF</title>
          <description>Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
        </group>
        <group group_id="B2">
          <title>Pegloticase + Placebo</title>
          <description>Participants randomized to this arm will receive pegloticase + placebo&#xD;
Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="32"/>
          </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="55" spread="9.4"/>
                    <measurement group_id="B2" value="55.5" spread="10.7"/>
                    <measurement group_id="B3" value="55.2" spread="9.7"/>
                  </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="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>American College of Rheumatology / European League Against Rheumatism Flare Criteria Score</title>
          <description>Maximum score is 23 points across 3 domains. Score of &gt;=8 classifies a subject as having gout&#xD;
Domains include 1) clinical parameters, 2) laboratory parameters and 3) imaging parameters. The specific domains and their respective definitions are available at https://ard.bmj.com/content/74/10/1789. Domains were designed to be scored based on the totality of the subjects' symptomatic disease experience. Categories within domains are hierarchical and mutually exclusive, such that if a higher and a lower category have been fulfilled at different points in time, the higher one should be scored.</description>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.5" spread="2.8"/>
                    <measurement group_id="B2" value="13.8" spread="2.7"/>
                    <measurement group_id="B3" value="13.5" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gout Flare History (flare within the last year)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of Gout</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.3" spread="9.8"/>
                    <measurement group_id="B2" value="13.4" spread="7.4"/>
                    <measurement group_id="B3" value="13.4" spread="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>PROMIS Pain Intensity</title>
          <description>The higher score the more severity PROMIS Pain scores raw ranges from 3 to 15 (convert to T-Score as minimum: 30.7 and maximum: 71.8)</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.8" spread="11.3"/>
                    <measurement group_id="B2" value="45.0" spread="12.4"/>
                    <measurement group_id="B3" value="49.0" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>PROMIS Physical Function</title>
          <description>Higher score worse outcome. PROMIS Physical Function raw ranges from 4 to 20 (convert to minimum: 22.9 and maximum: 56.9)</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.5" spread="7.8"/>
                    <measurement group_id="B2" value="33.8" spread="6.4"/>
                    <measurement group_id="B3" value="36.3" spread="8.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gout Impact Score</title>
          <description>The gout impact score is a disease-specific measure that adequately captures the impact of gout over time, and allows patients to describe the impact of gout on their health related quality of life.&#xD;
24 item questionnaire with responses on Likert-type scales (e.g., strongly agree to strongly disagree; all of the time to none of the time).The higher score the more severity. Score range: 0-96.</description>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.7" spread="7.5"/>
                    <measurement group_id="B2" value="46.4" spread="7.1"/>
                    <measurement group_id="B3" value="45.9" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum Urate Level</title>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.9" spread="1.8"/>
                    <measurement group_id="B2" value="9.8" spread="1.3"/>
                    <measurement group_id="B3" value="9.2" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>25 to &lt; 30</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>30 to &lt; 45</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥45</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Comorbidities</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Diabetes Mellitus /Metabolic Syndrome</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cerebral Vascular Vascular Disease/Heart Accident/Peripheral Vascular Disease</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Systemic Hypertension</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dyslipidemia</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Kidney Stones</title>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks</title>
        <description>Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.</description>
        <time_frame>12 weeks</time_frame>
        <population>32 participants received at least one dose of pegloticase and were included in modified intention-to-treat analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Pegloticase + MMF</title>
            <description>Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
          </group>
          <group group_id="O2">
            <title>Pegloticase + Placebo</title>
            <description>Participants randomized to this arm will receive pegloticase + placebo&#xD;
Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks</title>
          <description>Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.</description>
          <population>32 participants received at least one dose of pegloticase and were included in modified intention-to-treat analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="6"/>
                  </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>Fisher's exact tests were performed to compare baseline and clinical characteristics between treatment groups as appropriate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Efficacy of MMF was examined by the proportion of responders in MMF+Peg compared to PBO+Peg. Rates of the primary outcome were compared using proportions and 95% confidence intervals and tested for differences using Fisher's exact test.</non_inferiority_desc>
            <p_value>&lt;0.01</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>36 weeks</time_frame>
      <desc>Adverse event was defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Adverse Events were monitored/assessed based on organ system class.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pegloticase + MMF</title>
          <description>Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
MMF: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
        </group>
        <group group_id="E2">
          <title>Pegloticase + Placebo</title>
          <description>Participants randomized to this arm will receive pegloticase + placebo&#xD;
Placebo: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.&#xD;
Pegloticase 8 MG/ML [Krystexxa]: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Motor Vehicle Crash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion Reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (10.0)</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="15" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Other (Lab abnormality, anxiety, neurological, and oral pain)</sub_title>
                <counts group_id="E1" events="11" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal (arthralgia, myalgia, low back pain, orthopedic trauma, bursitis tendonitis)</sub_title>
                <counts group_id="E1" events="19" subjects_affected="9" subjects_at_risk="22"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jeff Foster</name_or_title>
      <organization>UNIVERSITY OF ALABAMA AT BIRMINGHAM</organization>
      <phone>2059966086</phone>
      <email>pjfoster@uabmc.edu</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/NCT03303989
org study id: 300000591
nct id: NCT03303989
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Pegloticase treatment for chronic refractory gout is limited by immunogenicity. The
      investigators propose the REduCing Immunogenicity to PegloticasE (RECIPE) trial to begin to
      investigate the question of whether a short course of immune modulating therapy with
      mycophenolate mofetil can significantly and safely attenuate immunogenicity to pegloticase
      and ensure patients afflicted with chronic refractory gout have better treatment outcomes and
      improved quality of life.
Pegloticase is highly efficacious therapy for chronic refractory gout patients (n = > 400K in
      the US alone). It decreases serum urate (sUA) levels to often undetectable levels and reduces
      tophi burden. However, its long-term real world effectiveness is severely limited due to its
      immunogenicity caused by anti-pegloticase antibody formation. REducing Immunogenicity to
      PEgloticase (RECIPE) is a Phase II, double-blind, placebo controlled, proof-of-concept trial
      in 32 subjects initiating pegloticase for treatment of chronic refractory gout. RECIPE will
      investigate the preliminary efficacy and safety of using immune modulating therapy with
      mycophenolate mofetil (MMF) to prevent immunogenicity conferred by pegloticase. Subjects will
      be randomized 3:1 to receive MMF vs. placebo in addition to everyone receiving pegloticase.
      The co-primary aims of the RECIPE trial are to 1) determine if a 12 week course of immune
      modulating therapy with daily MMF can safely and significantly attenuate immunogenicity to
      pegloticase as determined by the proportion of participants achieving and maintaining an sUA
      less than or equal to 6 mg/dL through 12 weeks, compared to concurrent controls, and 2) to
      assess the incidence and types of adverse events and infusion reaction. After 12 weeks of
      co-administration, all participants will continue on pegloticase for an additional 12 weeks
      without combination MMF immune modulating therapy to evaluate the longer term benefits
      (durability) and safety of this approach. The secondary aims are to: 1) Determine the 6 month
      durability of immune modulation after discontinuation of the short course of MMF by: a)
      assessing the absolute change in sUA from baseline to Week 24, and Week 12 to Week 24 and b)
      determining the proportion of participants with sUA ≤ 6 mg/dL through 24 weeks, and Week 12
      to Week 24; 2) Identify and characterize the pegloticase immune response by immunoglobulin
      isotypes (IgG and IgM), specificities, and antibody titer; and 3) Examine patient reported
      outcomes (PROs) using the NIH supported Patient Reported Outcomes Measurement Information
      System (PROMIS) and Gout Impact Scale (GIS) instruments. The University of Alabama at
      Birmingham (UAB) and the University of Michigan (UM), two large academic gout and immunology
      research centers, which in aggregate see nearly 10,000 gout patients annually, will serve as
      the two lead study sites and are very well-positioned to address the clinical and immunologic
      questions posed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase II, double blind, placebo controlled multisite proof-of-concept trial in subjects initiating pegloticase for treatment of chronic gout
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double blind
measure: Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks
time frame: 12 weeks
description: Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.
arm group label: pegloticase + MMF
arm group type: Experimental
description: Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.
arm group label: pegloticase + placebo
arm group type: Placebo Comparator
description: Participants randomized to this arm will receive pegloticase + placebo
intervention type: Drug
intervention name: Pegloticase 8 MG/ML [Krystexxa]
description: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
arm group label: pegloticase + MMF
other name: Krystexxa
intervention type: Drug
intervention name: MMF
description: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
arm group label: pegloticase + MMF
other name: Cell Cept
intervention type: Drug
intervention name: Placebo
description: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
arm group label: pegloticase + placebo
intervention type: Drug
intervention name: Pegloticase 8 MG/ML [Krystexxa]
description: Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
arm group label: pegloticase + placebo
other name: Krystexxa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kenneth G Saag, MD
role: Principal Investigator
affiliation: Professor
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Kenneth Saag, MD, MSc
investigator title: Professor of Medicine
mesh term: Mycophenolic Acid
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 