<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/NCT03002519</url>
  </required_header>
  <id_info>
    <org_study_id>PLX-R18-HCT-01</org_study_id>
    <nct_id>NCT03002519</nct_id>
  </id_info>
  <brief_title>Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation</brief_title>
  <official_title>A Phase I Open-label Dose-escalation Study to Evaluate the Safety of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pluristem Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pluristem Ltd.</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 study aims to evaluate the safety of intramuscular (IM) administration of PLX-R18 in&#xD;
      subjects with incomplete hematopoietic recovery following HCT.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2017</start_date>
  <completion_date type="Actual">October 30, 2021</completion_date>
  <primary_completion_date type="Actual">September 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Emergent Adverse Events (AEs)</measure>
    <time_frame>Recorded after time of consent throughout the study until the last visit (~1 year)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety laboratory values (including immunological testing)</measure>
    <time_frame>Blood samples will be collected on each visit, through study completion (~1 year)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs</measure>
    <time_frame>Will be assessed during each visit, through study completion (~1 year)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>ECG</measure>
    <time_frame>Will be assessed during the screening visit, before each IP treatment visit and on the 14th day of participation (visit 5).</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Incomplete HCT (Hematopoietic Cell Transplantation)</condition>
  <arm_group>
    <arm_group_label>PLX-R18</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation- first three subjects will be enrolled in the low dose cohort, 6 subjects in the intermediate-dose cohort, and 15 subjects in the high dose cohort.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PLX-R18</intervention_name>
    <description>Intramuscular (IM) administration of PLX-R18</description>
    <arm_group_label>PLX-R18</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years.&#xD;
&#xD;
          2. At least 3 months after HCT, either autologous or allogeneic (of any source, with any&#xD;
             preparatory regimen, for any indication), prior to study treatment.&#xD;
&#xD;
          3. Sustained platelet count ≤50,000/µL, and/or sustained Hb ≤8 g/dL and/or sustained ANC&#xD;
             ≤1000/mm3, attributed to graft failure as a major contributor, as evident by&#xD;
             hypocellular bone marrow.&#xD;
&#xD;
             Cytopenia should be confirmed by at least 2 consecutive blood counts, at least one of&#xD;
             them within 28 days prior to treatment (higher transient levels following occasional&#xD;
             blood product transfusions are allowed).&#xD;
&#xD;
          4. Stable donor cell chimerism in at least 3 consecutive tests prior to treatment (the&#xD;
             most recent test should be within 28 days prior to treatment).&#xD;
&#xD;
          5. If the subject had allogeneic HCT for a malignant disease, the subject should have&#xD;
             complete donor chimerism.&#xD;
&#xD;
             *complete donor chimerism should be determined by the investigator per site's&#xD;
             standards.&#xD;
&#xD;
          6. General performance status evaluated by Eastern Cooperative Oncology Group 0-2 scale.&#xD;
&#xD;
          7. Signed written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        INCLUSION AND EXCLUSION CRITERIA Inclusion Criteria&#xD;
&#xD;
        Subjects must meet all of the inclusion criteria listed below to be eligible for the study:&#xD;
&#xD;
          1. Age ≥18 years.&#xD;
&#xD;
          2. At least 3 months after HCT, either autologous or allogeneic (of any source, with any&#xD;
             preparatory regimen, for any indication), prior to study treatment.&#xD;
&#xD;
          3. Sustained platelet count ≤50,000/µL, and/or sustained Hb ≤8 g/dL and/or sustained ANC&#xD;
             ≤1000/mm3, attributed to graft failure as a major contributor, as evident by&#xD;
             hypocellular bone marrow.&#xD;
&#xD;
        Cytopenia should be confirmed by at least 2 consecutive blood counts, at least one of them&#xD;
        within 28 days prior to treatment (higher transient levels following occasional blood&#xD;
        product transfusions are allowed).&#xD;
&#xD;
        4. Stable donor cell chimerism in at least 3 consecutive tests prior to treatment (the most&#xD;
        recent test should be within 28 days prior to treatment).&#xD;
&#xD;
        5. If the subject had allogeneic HCT for a malignant disease, the subject should have&#xD;
        complete donor chimerism.&#xD;
&#xD;
        *complete donor chimerism should be determined by the investigator per site's standards.&#xD;
&#xD;
        6. General performance status evaluated by Eastern Cooperative Oncology Group 0-2 scale.&#xD;
&#xD;
        7. Signed written informed consent. Exclusion Criteria&#xD;
&#xD;
          1. Evidence of developing malignancy since the HCT, or any evidence of malignancy at the&#xD;
             time of screening.&#xD;
&#xD;
          2. Current active infection requiring systemic treatment (if infection resolved but&#xD;
             antibiotic coverage continues, patient may be included).&#xD;
&#xD;
          3. Acute graft versus host disease (GvHD) Grade III or IV, or severe chronic GvHD at the&#xD;
             time of screening.&#xD;
&#xD;
          4. Subject has received prophylactic treatment with donor lymphocyte infusion (DLI)&#xD;
             within 6 months prior to treatment, or any other cell therapy within 3 months prior to&#xD;
             treatment.&#xD;
&#xD;
          5. History of malignancy (other than the disease that required the HCT) within 2 years&#xD;
             prior to screening (except for skin basal cell carcinoma or squamous cell carcinoma&#xD;
             lesions that were fully resected with no need for further treatment, and not located&#xD;
             at the injection site).&#xD;
&#xD;
          6. History of significant transfusion reaction including: Transfusion related acute lung&#xD;
             injury (pulmonary edema), shock, severe disturbances of liver function tests, renal&#xD;
             dysfunction, or hemolytic anemia (as part of the transfusion reaction).&#xD;
&#xD;
          7. Known allergies to any of the following: dimethyl sulfoxide (DMSO), human serum&#xD;
             albumin, bovine serum albumin, gentamicin, or antihistamine.&#xD;
&#xD;
          8. History of allergic/hypersensitivity reaction to any substance having required&#xD;
             hospitalization and/or treatment with intra-venous steroids/epinephrine or in the&#xD;
             opinion of the Investigator the subject is at high risk of developing severe&#xD;
             allergic/hypersensitivity reactions (does not apply to transfusion reactions - see&#xD;
             exclusion criterion 8).&#xD;
&#xD;
          9. A known history of allergic/hypersensitivity reactions to 3 or more allergens.&#xD;
&#xD;
         10. History of uncontrolled asthma (Global Initiative for Asthma Grade III IV).&#xD;
&#xD;
         11. History of severe atopic disease (including but not limited to chronic urticaria,&#xD;
             allergic reaction with respiratory symptoms requiring systemic steroids).&#xD;
&#xD;
         12. Medical history of human immunodeficiency virus or syphilis infection.&#xD;
&#xD;
         13. Known active hepatitis B or hepatitis C infection at the time of screening.&#xD;
&#xD;
         14. A pregnant or lactating woman or a woman who plans to become pregnant during the&#xD;
             study. In addition, any woman of childbearing potential (not sterile or&#xD;
             postmenopausal), who is unwilling to adhere to the use of a highly effective&#xD;
             contraception method for the duration of the study:&#xD;
&#xD;
               1. Oral/intravaginal/transdermal combined estrogen and progestogen containing&#xD;
                  hormonal contraception for at least 3 months prior to screening.&#xD;
&#xD;
               2. Oral/injectable/implantable progestogen-only hormonal contraception for at least&#xD;
                  3 months prior to screening.&#xD;
&#xD;
               3. An intrauterine device (IUD) or intrauterine hormone-releasing system (IUS).&#xD;
&#xD;
         15. Subjects on renal replacement therapy or with estimated glomerular filtration rate&#xD;
             (eGFR) &lt;15 mL/min/1.73m2 (based on Modification of Diet in Renal Disease [MDRD]&#xD;
             equation).&#xD;
&#xD;
         16. Serum glutamic pyruvic transaminase (alanine aminotransferase), serum oxaloacetic&#xD;
             pyruvic transaminase (aspartate aminotransferase) &gt;2.5 x upper limit of normal range.&#xD;
&#xD;
         17. International normalized ratio (INR) &gt;2 or subjects who are on oral anticoagulant&#xD;
             therapy with INR &gt;2 unless anticoagulation treatment can be safely&#xD;
             interrupted/discontinued around each investigational product (IP) treatment upon&#xD;
             primary care physician and/or Investigator's discretion.&#xD;
&#xD;
         18. Severe or uncontrolled/unstable cardiac, pulmonary, or renal disease, including&#xD;
             myocardial infarction or cerebrovascular accident within 3 months prior to treatment.&#xD;
&#xD;
         19. History of solid organ transplantation.&#xD;
&#xD;
         20. Signs and symptoms of active central nervous system disease.&#xD;
&#xD;
         21. Life expectancy &lt;6 months as assessed by the Investigator.&#xD;
&#xD;
         22. Subject has participated in a clinical interventional study and received the last&#xD;
             treatment within 30 days prior to screening.&#xD;
&#xD;
         23. In the opinion of the Investigator, the subject is unsuitable for participating in 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>
  <location>
    <facility>
      <name>The University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1447</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center - The Richard and Annette Bloch Cancer Care Pavilion,2330 Shawnee Mission Parkway</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205-2005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center,22 South Greene Street</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Cancer Center (MCCC) - Rochester,200 1st Street SW</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Ein Karem Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center</name>
      <address>
        <city>Ramat Gan</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>December 15, 2022</last_update_submitted>
  <last_update_submitted_qc>December 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03002519
org study id: PLX-R18-HCT-01
nct id: NCT03002519
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study aims to evaluate the safety of intramuscular (IM) administration of PLX-R18 in
      subjects with incomplete hematopoietic recovery following HCT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Emergent Adverse Events (AEs)
time frame: Recorded after time of consent throughout the study until the last visit (~1 year)
measure: Safety laboratory values (including immunological testing)
time frame: Blood samples will be collected on each visit, through study completion (~1 year)
measure: Vital signs
time frame: Will be assessed during each visit, through study completion (~1 year)
measure: ECG
time frame: Will be assessed during the screening visit, before each IP treatment visit and on the 14th day of participation (visit 5).
arm group label: PLX-R18
arm group type: Experimental
description: Dose Escalation- first three subjects will be enrolled in the low dose cohort, 6 subjects in the intermediate-dose cohort, and 15 subjects in the high dose cohort.
intervention type: Biological
intervention name: PLX-R18
description: Intramuscular (IM) administration of PLX-R18
arm group label: PLX-R18
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Israel
country: United States
responsible party type: Sponsor