<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/NCT03797040</url>
  </required_header>
  <id_info>
    <org_study_id>PLX-R18-ARS-01</org_study_id>
    <nct_id>NCT03797040</nct_id>
  </id_info>
  <brief_title>Open-label Phase I Study for PEP or Treatment of HS-ARS PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS)</brief_title>
  <acronym>HS-ARS</acronym>
  <official_title>Open-label Phase I Study to Evaluate the Safety of PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pluristem Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pluristem Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the study is to evaluate the safety of intramuscular (IM) administration of&#xD;
      PLX-R18 in subjects exposed to ionizing radiation and who are at risk of developing HS-ARS.&#xD;
&#xD;
      Indication:Post-Exposure Prevention (PEP) or treatment of Hematopoietic Syndrome of Acute&#xD;
      Radiation Syndrome (HS-ARS) in subjects suspected to have been exposed to ionizing radiation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a Phase I, open-label safety study; each subject will receive two&#xD;
      administrations of PLX-R18, 4 days apart. Each administration of PLX-R18 will contain 4&#xD;
      million cells/kg (up to a maximal dose of 400 million cells). The first administration should&#xD;
      be preferably within 48 hours after suspected exposure and no later than 4 days after&#xD;
      suspected exposure. The second administration will be provided 4 days after first&#xD;
      administration.&#xD;
&#xD;
      All subjects will be hospitalized for at least 24 hours after each administration of&#xD;
      PLX-R18,for close monitoring.In order to minimize risks, subjects will be divided in 3&#xD;
      sequential cohorts:&#xD;
&#xD;
      Cohort 1: 9 subjects, treated as soon as possible Cohort 2: 18 subjects, treated at least 12&#xD;
      hours following the first dose administered to the 9th subject Cohort 3: 33 subjects, treated&#xD;
      at least 12 hours following the first dose administered to the 27th subject After the&#xD;
      completion of each Cohort, stopping rules will be assessed. All subjects will receive PLX-R18&#xD;
      in addition to recommended care per physician discretion, based on the REMM guidelines&#xD;
      (APPENDIX 2).&#xD;
&#xD;
      The study will be comprised of 2 periods:&#xD;
&#xD;
      Main study period - Subjects will be followed-up for 12 months and evaluated at the following&#xD;
      time points after the first administration: Day 0 (first administration),Day 1, Day 2, Day 3,&#xD;
      Day 4 (second administration), Day 5, Day 14 (2 weeks),Day 21 (3 weeks), Day 28 (4 weeks),&#xD;
      Day 49 (7 weeks), Day 63 (9 weeks), Day 119(17 weeks), Day 182 (26 weeks), and Day 364 (52&#xD;
      weeks).Long-term survival follow-up -Week 52 to Week 260: During this period, patients will&#xD;
      be followed-up for overall survival at: 104 weeks, 156 weeks, 208 weeks and 260 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 2021</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Any Adverse Reaction</measure>
    <time_frame>From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recovered with no sequelae</measure>
    <time_frame>From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)</time_frame>
    <description>The subject has fully recovered from the AE with no residual effects observable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recovered with sequelae</measure>
    <time_frame>From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)</time_frame>
    <description>The event resolved but the subject has sequelae, which is a condition following a consequence of a disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ongoing AE</measure>
    <time_frame>From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)</time_frame>
    <description>AE is still ongoing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">27</enrollment>
  <condition>Ionizing Radiation Exposure</condition>
  <arm_group>
    <arm_group_label>4 million PLX-R18 cells/kg-up to a maximal dose of 400 million</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cell therapy</intervention_name>
    <description>PLX-R18: Allogeneic ex vivo expanded placental stromal cells</description>
    <arm_group_label>4 million PLX-R18 cells/kg-up to a maximal dose of 400 million</arm_group_label>
    <other_name>PLX-R18</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject was exposed or suspected to have been exposed to ionizing radiation of&#xD;
&#xD;
             ≥1Gy and is at risk of developing HS-ARS, as assessed by the treating physician, based&#xD;
             on REMM guidelines (see APPENDIX 1).&#xD;
&#xD;
          2. PLX-R18 treatment can be initiated within 4 days of exposure.&#xD;
&#xD;
          3. Aged ≥18 years.&#xD;
&#xD;
          4. Has provided informed consent. -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known active malignancy or history of malignancy within 3 years prior to screening&#xD;
             except for successfully resected skin basal cell carcinoma or skin squamous cell&#xD;
             carcinoma not located at the injection sites.&#xD;
&#xD;
          2. Known active uncontrolled infection (e.g. viral, fungal, and/or bacterial)&#xD;
&#xD;
          3. Known active infection with Hepatitis A, B, or C.&#xD;
&#xD;
          4. Pregnancy.&#xD;
&#xD;
          5. Known hypersensitivity to: Allogeneic stromal cells, dimethyl sulfoxid (DMSO), human&#xD;
             serum albumin, or bovine products.&#xD;
&#xD;
          6. In the opinion of the Investigator the subject is at high risk of developing severe&#xD;
             allergic/hypersensitivity reactions and a resuscitation kit including epinephrine is&#xD;
             not at hand.&#xD;
&#xD;
          7. In the opinion of the treating physician, the subject is unsuitable for participating&#xD;
             in the study.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2020</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>Radiation Injuries</mesh_term>
    <mesh_term>Acute Radiation Syndrome</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/NCT03797040
org study id: PLX-R18-ARS-01
nct id: NCT03797040
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The objective of the study is to evaluate the safety of intramuscular (IM) administration of
      PLX-R18 in subjects exposed to ionizing radiation and who are at risk of developing HS-ARS.

      Indication:Post-Exposure Prevention (PEP) or treatment of Hematopoietic Syndrome of Acute
      Radiation Syndrome (HS-ARS) in subjects suspected to have been exposed to ionizing radiation.
This will be a Phase I, open-label safety study; each subject will receive two
      administrations of PLX-R18, 4 days apart. Each administration of PLX-R18 will contain 4
      million cells/kg (up to a maximal dose of 400 million cells). The first administration should
      be preferably within 48 hours after suspected exposure and no later than 4 days after
      suspected exposure. The second administration will be provided 4 days after first
      administration.

      All subjects will be hospitalized for at least 24 hours after each administration of
      PLX-R18,for close monitoring.In order to minimize risks, subjects will be divided in 3
      sequential cohorts:

      Cohort 1: 9 subjects, treated as soon as possible Cohort 2: 18 subjects, treated at least 12
      hours following the first dose administered to the 9th subject Cohort 3: 33 subjects, treated
      at least 12 hours following the first dose administered to the 27th subject After the
      completion of each Cohort, stopping rules will be assessed. All subjects will receive PLX-R18
      in addition to recommended care per physician discretion, based on the REMM guidelines
      (APPENDIX 2).

      The study will be comprised of 2 periods:

      Main study period - Subjects will be followed-up for 12 months and evaluated at the following
      time points after the first administration: Day 0 (first administration),Day 1, Day 2, Day 3,
      Day 4 (second administration), Day 5, Day 14 (2 weeks),Day 21 (3 weeks), Day 28 (4 weeks),
      Day 49 (7 weeks), Day 63 (9 weeks), Day 119(17 weeks), Day 182 (26 weeks), and Day 364 (52
      weeks).Long-term survival follow-up -Week 52 to Week 260: During this period, patients will
      be followed-up for overall survival at: 104 weeks, 156 weeks, 208 weeks and 260 weeks.
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Any Adverse Reaction
time frame: From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
measure: Recovered with no sequelae
time frame: From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
description: The subject has fully recovered from the AE with no residual effects observable.
measure: Recovered with sequelae
time frame: From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
description: The event resolved but the subject has sequelae, which is a condition following a consequence of a disease
measure: Ongoing AE
time frame: From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
description: AE is still ongoing
measure: Overall survival
time frame: From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
description: Overall survival
arm group label: 4 million PLX-R18 cells/kg-up to a maximal dose of 400 million
arm group type: Experimental
intervention type: Biological
intervention name: Cell therapy
description: PLX-R18: Allogeneic ex vivo expanded placental stromal cells
arm group label: 4 million PLX-R18 cells/kg-up to a maximal dose of 400 million
other name: PLX-R18
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Radiation Injuries
mesh term: Acute Radiation Syndrome
sharing ipd: No