<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/NCT03763318</url>
  </required_header>
  <id_info>
    <org_study_id>EQ001-aGVHD-001</org_study_id>
    <nct_id>NCT03763318</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity of EQ001 in Subjects With aGVHD</brief_title>
  <acronym>EQUATE</acronym>
  <official_title>A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects With Newly Diagnosed Acute Graft Versus Host Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Equillium</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Biocon Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Equillium</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 multi-center study to evaluate the safety, tolerability, PK, PD, and clinical&#xD;
      activity of EQ001 in subjects with Acute Graft Versus Host Disease (aGVHD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will enroll approximately 100 subjects in two (2) parts:&#xD;
&#xD;
      Part A is an open label study and will enroll approximately 40 evaluable subjects with aGVHD&#xD;
      across 4 cohorts. The total number of patients will depend on the number of dose escalations&#xD;
      necessary to enable a decision to be made on the recommended dose to take forward into Part B&#xD;
      of the study. The planned dose escalation will start with cohort 1, where subjects will&#xD;
      receive EQ001 administered intravenously every two weeks for a total of 5 doses.&#xD;
&#xD;
      Part B is a randomized, double-blind, placebo-controlled study and will enroll approximately&#xD;
      60 additional subjects, randomized in a 2:1 ratio to either active treatment EQ001 (40) or&#xD;
      placebo (20). Subjects will receive either EQ001 or placebo administered intravenously every&#xD;
      two weeks for a total of 5 doses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2019</start_date>
  <completion_date type="Actual">November 21, 2022</completion_date>
  <primary_completion_date type="Actual">November 21, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Part A is an open label 3+3 dose escalation Part B is blinded and randomized 2:1</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Part B will be blinded to all study staff that has direct access to the subjects and the sponsor. The site's pharmacist or designee will be unblinded to prepare the study drug.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment Emergent Adverse Events</measure>
    <time_frame>Study Day 85</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in aGVHD organ stages and overall clinical grading, aGVHD-AI</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Clinical activity will be assessed by change from baseline in aGVHD organ stages and overall clinical grading, aGVHD-AI, concomitant medication usage and disease progression assessments</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to maximum EQ001serum concentration, Tmax</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Time to maximum EQ001 serum concentration, Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum EQ001 serum drug concentration, Cmax</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Maximum EQ001 serum drug concentration, Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum EQ001 serum drug concentration, Cmin</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Minimum EQ001 serum drug concentration prior to next dose, Cmin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total EQ001 exposure across time, AUC (from zero to infinity)</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Total EQ001 exposure across time, AUC (from zero to infinity)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half life of EQ001, t1/2</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Half life of EQ001, t1/2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution of EQ001, Vd</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Volume of distribution of EQ001, Vd</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance, Cl</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Clearance, Cl</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Markers</measure>
    <time_frame>Study Day 337</time_frame>
    <description>Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD6 receptor expression levels</measure>
    <time_frame>Study Day 337</time_frame>
    <description>CD6 receptor expression levels</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Acute-graft-versus-host Disease</condition>
  <condition>aGVHD</condition>
  <condition>GVHD</condition>
  <condition>GVHD, Acute</condition>
  <arm_group>
    <arm_group_label>EQ001 Dose Escalation (Part A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EQ001 (Part B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EQ001 administered in a blinded fashion using the optimal dose selected from Part A by intravenous infusion every two weeks for a total of 5 doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EQ001 Placebo (Part B)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered in a blinded fashion by intravenous infusion every two weeks for a total of 5 doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EQ001</intervention_name>
    <description>Itolizumab [Bmab 600])</description>
    <arm_group_label>EQ001 (Part B)</arm_group_label>
    <arm_group_label>EQ001 Dose Escalation (Part A)</arm_group_label>
    <other_name>Bmab600</other_name>
    <other_name>Itolizumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>EQ001 Placebo</intervention_name>
    <description>EQ001 Placebo</description>
    <arm_group_label>EQ001 Placebo (Part B)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subject at least 18 years of age for Part A, and at least 12 years of&#xD;
             age for Part B.&#xD;
&#xD;
          2. Recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) using&#xD;
             myeloablative or non myeloablative conditioning regimens.&#xD;
&#xD;
          3. Have a clinical diagnosis of acute GVHD requiring systemic immune suppressive therapy.&#xD;
&#xD;
          4. Deemed by the investigator to be likely to comply with the planned procedure as&#xD;
             required by the protocol for the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of morphologic relapsed primary malignancy, treatment for relapse after&#xD;
             alloHSCT was performed, or requirement for rapid immunosuppressive treatment&#xD;
             withdrawal for early malignancy relapse.&#xD;
&#xD;
          2. Evidence of graft failure based on cytopenia(s), and as determined by the&#xD;
             investigator.&#xD;
&#xD;
          3. Evidence of post-transplant lymphoproliferative disease.&#xD;
&#xD;
          4. Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or&#xD;
             systemically administered corticosteroids.&#xD;
&#xD;
          5. As determined by the investigator, any medical, psychiatric, or other condition or&#xD;
             circumstance that is likely to negatively affect: the subject's participation in this&#xD;
             clinical study, the subject's safety, or the reliability of the study data.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joel Rothman</last_name>
    <role>Study Director</role>
    <affiliation>Equillium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health Shands Hospital</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami - Miller School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center &amp; Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan - C.S. Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University and Barnes Jewish Heart &amp; Vascular Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania, Abramson Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriStar Centennial Medical Center (SCRI)</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>53719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Healthcare</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109-4433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://equilliumbio.com</url>
    <description>Company website</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_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/NCT03763318
org study id: EQ001-aGVHD-001
nct id: NCT03763318
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical
      activity of EQ001 in subjects with Acute Graft Versus Host Disease (aGVHD).
The study will enroll approximately 100 subjects in two (2) parts:

      Part A is an open label study and will enroll approximately 40 evaluable subjects with aGVHD
      across 4 cohorts. The total number of patients will depend on the number of dose escalations
      necessary to enable a decision to be made on the recommended dose to take forward into Part B
      of the study. The planned dose escalation will start with cohort 1, where subjects will
      receive EQ001 administered intravenously every two weeks for a total of 5 doses.

      Part B is a randomized, double-blind, placebo-controlled study and will enroll approximately
      60 additional subjects, randomized in a 2:1 ratio to either active treatment EQ001 (40) or
      placebo (20). Subjects will receive either EQ001 or placebo administered intravenously every
      two weeks for a total of 5 doses.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Part A is an open label 3+3 dose escalation Part B is blinded and randomized 2:1
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Part B will be blinded to all study staff that has direct access to the subjects and the sponsor. The site's pharmacist or designee will be unblinded to prepare the study drug.
measure: Incidence of Treatment Emergent Adverse Events
time frame: Study Day 85
description: Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
measure: Change from baseline in aGVHD organ stages and overall clinical grading, aGVHD-AI
time frame: Study Day 337
description: Clinical activity will be assessed by change from baseline in aGVHD organ stages and overall clinical grading, aGVHD-AI, concomitant medication usage and disease progression assessments
measure: Time to maximum EQ001serum concentration, Tmax
time frame: Study Day 337
description: Time to maximum EQ001 serum concentration, Tmax
measure: Maximum EQ001 serum drug concentration, Cmax
time frame: Study Day 337
description: Maximum EQ001 serum drug concentration, Cmax
measure: Minimum EQ001 serum drug concentration, Cmin
time frame: Study Day 337
description: Minimum EQ001 serum drug concentration prior to next dose, Cmin
measure: Total EQ001 exposure across time, AUC (from zero to infinity)
time frame: Study Day 337
description: Total EQ001 exposure across time, AUC (from zero to infinity)
measure: Half life of EQ001, t1/2
time frame: Study Day 337
description: Half life of EQ001, t1/2
measure: Volume of distribution of EQ001, Vd
time frame: Study Day 337
description: Volume of distribution of EQ001, Vd
measure: Clearance, Cl
time frame: Study Day 337
description: Clearance, Cl
measure: Inflammatory Markers
time frame: Study Day 337
description: Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein
measure: CD6 receptor expression levels
time frame: Study Day 337
description: CD6 receptor expression levels
arm group label: EQ001 Dose Escalation (Part A)
arm group type: Experimental
description: Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses.
arm group label: EQ001 (Part B)
arm group type: Experimental
description: EQ001 administered in a blinded fashion using the optimal dose selected from Part A by intravenous infusion every two weeks for a total of 5 doses.
arm group label: EQ001 Placebo (Part B)
arm group type: Placebo Comparator
description: Placebo administered in a blinded fashion by intravenous infusion every two weeks for a total of 5 doses.
intervention type: Biological
intervention name: EQ001
description: Itolizumab [Bmab 600])
arm group label: EQ001 (Part B)
arm group label: EQ001 Dose Escalation (Part A)
other name: Bmab600
other name: Itolizumab
intervention type: Biological
intervention name: EQ001 Placebo
description: EQ001 Placebo
arm group label: EQ001 Placebo (Part B)
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Joel Rothman
role: Study Director
affiliation: Equillium
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://equilliumbio.com
description: Company website
responsible party type: Sponsor
mesh term: Graft vs Host Disease
sharing ipd: No