<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/NCT04450654</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00009143</org_study_id>
    <nct_id>NCT04450654</nct_id>
  </id_info>
  <brief_title>Monotherapy IVIG Gamunex-C for HMG-CoA Reductase Auto-Antibody Positive Necrotizing Myopathy Treatment (The MIGHT Trial)</brief_title>
  <official_title>Monotherapy IVIG Gamunex-C for HMG-CoA Reductase Auto-Antibody Positive Necrotizing Myopathy Treatment (The MIGHT Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Grifols Biologicals, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</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>
      This is a phase 2, pilot, randomized, placebo-controlled trial of Gamunex-C IVIG as&#xD;
      mono-therapy for HMGCoA reductase auto-antibody positive (HMGCR) necrotizing myopathy. The&#xD;
      trial will test the feasibility and initial efficacy of Gamunex-C IVIG mono-therapy in HMGCR&#xD;
      necrotizing myopathy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 2, double-blinded, randomized, placebo-controlled, multi-center trial of&#xD;
      Gamunex-C IVIG as mono-therapy for HMGCR necrotizing myopathy. Up to 10 treatment-naïve&#xD;
      patients will be enrolled and randomized to receive either Gamunex-C IVIG dosed at 2g/kg or&#xD;
      placebo at week 0 and week 4. The primary efficacy outcome is the percentage of patients at&#xD;
      week 8 with at least minimal improvement per the 2016 ACR/EULAR myositis clinical response&#xD;
      criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No Participants Enrolled&#xD;
  </why_stopped>
  <start_date type="Anticipated">May 2022</start_date>
  <completion_date type="Actual">July 25, 2022</completion_date>
  <primary_completion_date type="Actual">July 25, 2022</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>This is a randomized, double-blinded, placebo-controlled phase 2 trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ACR/EULAR 2016 Clinical Response Criteria for Myositis</measure>
    <time_frame>week 8</time_frame>
    <description>The percentage of patients in each arm with at least a minimal response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Manual Muscle Strength Testing (MMT-8) score</measure>
    <time_frame>week 8</time_frame>
    <description>Manual muscle strength testing in 8 muscle groups will be scored. Range 0-160, with higher scores reflecting increased muscle strength.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ACR/EULAR Clinical Response Criteria for Myositis Total Improvement Score</measure>
    <time_frame>week 8</time_frame>
    <description>The total improvement score based on ACR/EULAR 2016 criteria will be calculated. Range 0-100, with higher scores reflecting greater improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HMG-CoA Reductase Auto-antibody titer level</measure>
    <time_frame>week 8</time_frame>
    <description>Autoantibody titer level will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creatine kinase</measure>
    <time_frame>week 8</time_frame>
    <description>Serum creatine kinase level will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients screened to achieve planned enrollment</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days needed to enroll planned sample</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of enrolled patients completing all primary and secondary measures</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Immune-Mediated Necrotizing Myopathy</condition>
  <arm_group>
    <arm_group_label>Gamunex-C IVIG</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gamunex-C IVIG dosed at 2g/kg will be given on week 0 and week 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Albumin in a 1% solution at an equivalent volume to the corresponding Gamunex-C IVIG dose will be given at week 0 and week 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gamunex-C</intervention_name>
    <description>Gamunex-C IVIG will be given at week 0 and week 4</description>
    <arm_group_label>Gamunex-C IVIG</arm_group_label>
    <other_name>IVIG</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albumin</intervention_name>
    <description>1% albumin solution dosed at equivalent volume to the corresponding weight-based Gamunex-C IVIG dose will be given at week 0 and week 4</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        A subject must meet all of the following inclusion criteria at screening to be eligible for&#xD;
        participation in this study:&#xD;
&#xD;
          -  Anti-HMGCR positive. Patients will be screened by commercially-available ELISA.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Demonstrable proximal muscle weakness: score of &lt;135 on the Proximal Manual Muscle&#xD;
             Strength Testing 8-Muscle Group Assessment (MMT-8) (range 0-160).&#xD;
&#xD;
          -  Serum creatinine kinase (CK) more than 5 times the upper limit of normal&#xD;
&#xD;
          -  Muscle biopsy will not be required for eligibility in order to minimize the time to&#xD;
             enrollment and initiation of treatment. Muscle biopsy will be obtained whenever&#xD;
             possible as part of the standard of care.&#xD;
&#xD;
          -  Subjects must be willing and able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A subject meeting any of the following exclusion criteria at screening is NOT eligible for&#xD;
        participation in this study:&#xD;
&#xD;
          -  Disease duration greater than 36 months.&#xD;
&#xD;
          -  Participants taking oral or intravenous glucocorticoids where the dose has changed&#xD;
             within 4 weeks of screening.&#xD;
&#xD;
          -  Exposure to immunoglobulin treatment (IV, IM, or SubQ) in the prior 3 months&#xD;
&#xD;
          -  Exposure to plasma exchange (PEX) in the prior 3 months&#xD;
&#xD;
          -  Exposure to other immunosuppressive medications (e.g. methotrexate, leflunomide,&#xD;
             azathioprine, mycophenolate mofetil) in the prior 6 months&#xD;
&#xD;
          -  Exposure to rituximab or any monoclonal antibody in the prior 12 months&#xD;
&#xD;
          -  Currently taking a statin medication&#xD;
&#xD;
          -  History of dermatomyositis rash (either biopsy-proven, or history of photosensitive&#xD;
             rash).&#xD;
&#xD;
          -  Presence of respiratory or swallowing dysfunction due to HMGCR myopathy&#xD;
&#xD;
          -  Inadequate venous access&#xD;
&#xD;
          -  History of anaphylactic reactions or severe reactions to any blood-derived product&#xD;
&#xD;
          -  History of intolerance to any component of the IP&#xD;
&#xD;
          -  History of thrombotic complication to polyclonal IVIG therapy&#xD;
&#xD;
          -  History of pulmonary embolism or deep venous thromboembolism&#xD;
&#xD;
          -  History of hyperviscosity or hypercoagulable state&#xD;
&#xD;
          -  History of myocardial infarction or stroke in the last 12 months&#xD;
&#xD;
          -  Currently receiving anti-coagulation therapy (vitamin K antagonists, non-vitamin K&#xD;
             oral anticoagulants [e.g. dabigatran, rivaroxaban, apixaban], parenteral&#xD;
             anticoagulants [e.g fondaparinux]. Note that oral anti-platelet agents are allowed&#xD;
             (e.g. aspirin, clopidogrel, ticodipine).&#xD;
&#xD;
          -  Females of child-bearing potential who are pregnant, have a positive serum pregnancy&#xD;
             test (human chorionic gonadotropin [HCG]-based assay), breastfeeding, or are unwilling&#xD;
             to practice a highly effective method of contraception (oral, injectable or implanted&#xD;
             hormonal methods of contraception, placement of an intrauterine device or intrauterine&#xD;
             system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male&#xD;
             sterilization, or true abstinence*) throughout the study.&#xD;
&#xD;
             * True abstinence: When this is in line with the preferred and usual lifestyle of the&#xD;
             subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal,&#xD;
             post-ovulation methods], declaration of abstinence for the duration of a trial, and&#xD;
             withdrawal are not acceptable methods of contraception.)&#xD;
&#xD;
          -  Renal impairment (i.e., estimated glomerular filtration rate (eGFR) below 60ml/min)&#xD;
&#xD;
          -  History of chronic liver disease&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding&#xD;
             more than 2.5 times the ULN for the expected normal range for the testing laboratory,&#xD;
             not due to HMGCR myopathy.&#xD;
&#xD;
          -  Hemoglobin level &lt;9 g/dL&#xD;
&#xD;
          -  Known Immunoglobulin A (IgA) deficiency and anti-IgA serum antibodies&#xD;
&#xD;
          -  History of chronic alcoholism or illicit drug abuse (addiction) in the prior 12 months&#xD;
&#xD;
          -  Active psychiatric illness that interferes with compliance or communication with&#xD;
             healthcare personnel&#xD;
&#xD;
          -  Currently receiving, or having received, within 1 month prior any investigational&#xD;
             medicinal product or device. In the case of an investigational medicinal product&#xD;
             trial, at least five half- lives (if known) must have elapsed prior to Screening.&#xD;
&#xD;
          -  Any medical condition which makes the clinical trial participation unadvisable or&#xD;
             which is likely to interfere with the evaluation of the study treatment and/or the&#xD;
             satisfactory conduct of the clinical trial according to the investigator's judgment.&#xD;
             Any factor that in the opinion of the investigator would compromise the ability of the&#xD;
             subject to complete the trial&#xD;
&#xD;
          -  Weight &gt; 120kg. Individuals weighing &gt;100kg and ≤120kg will be eligible at the&#xD;
             discretion of the investigators.&#xD;
&#xD;
          -  History of angina pectoris or transient ischemic attack (TIA) in the last 12 months&#xD;
&#xD;
          -  Wells Criteria Score for DVT of 2 or more at the time of screening.&#xD;
&#xD;
          -  Wells Criteria Score for PE of 4 or more at the time of screening.&#xD;
&#xD;
          -  Presence of a central, in-dwelling catheter (such as a PICC line) at the time of&#xD;
             informed consent.&#xD;
&#xD;
          -  Currently taking a nephrotoxic drug (eg gentamicin or vancomycin) at the time of&#xD;
             informed consent.&#xD;
&#xD;
          -  Severe cardiac failure at the time of informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>120 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James S Andrews, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Washington</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>October 19, 2022</last_update_submitted>
  <last_update_submitted_qc>October 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>James S. Andrews</investigator_full_name>
    <investigator_title>Assistant Professor, School of Medicine: Rheumatology</investigator_title>
  </responsible_party>
  <keyword>HMG-CoA Reductase Auto-Antibody Necrotizing Myopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04450654
org study id: STUDY00009143
nct id: NCT04450654
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 2, pilot, randomized, placebo-controlled trial of Gamunex-C IVIG as
      mono-therapy for HMGCoA reductase auto-antibody positive (HMGCR) necrotizing myopathy. The
      trial will test the feasibility and initial efficacy of Gamunex-C IVIG mono-therapy in HMGCR
      necrotizing myopathy.
This is a phase 2, double-blinded, randomized, placebo-controlled, multi-center trial of
      Gamunex-C IVIG as mono-therapy for HMGCR necrotizing myopathy. Up to 10 treatment-naïve
      patients will be enrolled and randomized to receive either Gamunex-C IVIG dosed at 2g/kg or
      placebo at week 0 and week 4. The primary efficacy outcome is the percentage of patients at
      week 8 with at least minimal improvement per the 2016 ACR/EULAR myositis clinical response
      criteria.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, double-blinded, placebo-controlled phase 2 trial.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ACR/EULAR 2016 Clinical Response Criteria for Myositis
time frame: week 8
description: The percentage of patients in each arm with at least a minimal response
measure: Manual Muscle Strength Testing (MMT-8) score
time frame: week 8
description: Manual muscle strength testing in 8 muscle groups will be scored. Range 0-160, with higher scores reflecting increased muscle strength.
measure: ACR/EULAR Clinical Response Criteria for Myositis Total Improvement Score
time frame: week 8
description: The total improvement score based on ACR/EULAR 2016 criteria will be calculated. Range 0-100, with higher scores reflecting greater improvement.
measure: HMG-CoA Reductase Auto-antibody titer level
time frame: week 8
description: Autoantibody titer level will be assessed
measure: Creatine kinase
time frame: week 8
description: Serum creatine kinase level will be measured
measure: Number of patients screened to achieve planned enrollment
time frame: 2 years
measure: Number of days needed to enroll planned sample
time frame: 2 years
measure: Percentage of enrolled patients completing all primary and secondary measures
time frame: 2 years
arm group label: Gamunex-C IVIG
arm group type: Experimental
description: Gamunex-C IVIG dosed at 2g/kg will be given on week 0 and week 4.
arm group label: Placebo
arm group type: Placebo Comparator
description: Albumin in a 1% solution at an equivalent volume to the corresponding Gamunex-C IVIG dose will be given at week 0 and week 4.
intervention type: Drug
intervention name: Gamunex-C
description: Gamunex-C IVIG will be given at week 0 and week 4
arm group label: Gamunex-C IVIG
other name: IVIG
intervention type: Drug
intervention name: Albumin
description: 1% albumin solution dosed at equivalent volume to the corresponding weight-based Gamunex-C IVIG dose will be given at week 0 and week 4
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 120 Years
healthy volunteers: No
last name: James S Andrews, MD
role: Principal Investigator
affiliation: University of Washington
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: James S. Andrews
investigator title: Assistant Professor, School of Medicine: Rheumatology
mesh term: Muscular Diseases
mesh term: Immunoglobulins, Intravenous