<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/NCT03840512</url>
  </required_header>
  <id_info>
    <org_study_id>KAL05</org_study_id>
    <nct_id>NCT03840512</nct_id>
  </id_info>
  <brief_title>An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)</brief_title>
  <official_title>A Phase 2a, Open-label, Multicenter, Study to Evaluate the Pharmacokinetic (PK), Safety and Efficacy of Multiple Doses of Cannabidiol for the Prevention of aGVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kalytera Therapeutics Israel, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kalytera Therapeutics Israel, Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, open-label, phase 2a study, to evaluate the pharmacokinetic (PK) profile,&#xD;
      safety, and efficacy of multiple doses of Cannabidiol (CBD) in participants Graft-Versus-Host&#xD;
      Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study contains 3 cohorts of 12 participants each: All participants will be orally&#xD;
      administered for 105 days with CBD at doses of 75, 150 or 300 mg (PO) BID for the prevention&#xD;
      of acute GVHD (aGVHD) following allogeneic HSCT.&#xD;
&#xD;
      In addition to the study drug, all participants will receive standard aGVHD prophylaxis&#xD;
      consisting of a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of&#xD;
      methotrexate (MTX). After completion of 105 treatment days, the participant will be&#xD;
      followed-up until day 180.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 12, 2018</start_date>
  <completion_date type="Anticipated">December 15, 2022</completion_date>
  <primary_completion_date type="Anticipated">November 15, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events (AEs) and serious adverse events (SAEs) Reporting</measure>
    <time_frame>Up to day 180</time_frame>
    <description>All AEs will be recorded, whether considered minor or serious, drug-related or not</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative incidence of aGVHD at day 100 post-transplant</measure>
    <time_frame>First 100 days after transplant</time_frame>
    <description>Cumulative Incidence of Grade B-D aGvHD</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile - AUC0-t - area under the plasma concentration-time curve (AUC0-t) up to the last quantifiable concentration (LOQ) from time of administration (t=0) up to the selected</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - λz</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞</measure>
    <time_frame>Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD</time_frame>
    <description>Pharmacokinetic (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative incidence of aGVHD at day 180 post-transplant</measure>
    <time_frame>Day 180 post-transplant</time_frame>
    <description>Cumulative Incidence of Grade 2-4 aGvHD</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Prevention aGVHD</condition>
  <arm_group>
    <arm_group_label>Oral CBD 75 BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral CBD 150 BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral CBD 300 BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CBD</intervention_name>
    <description>CBD + Standard aGVHD prophylaxis calcineurin inhibitor (cyclosporine or tacrolimus) + methotrexate (MTX).&#xD;
Subjects transplanted from unrelated donors or from mismatched siblings will also receive anti-T cell globulin.</description>
    <arm_group_label>Oral CBD 150 BID</arm_group_label>
    <arm_group_label>Oral CBD 300 BID</arm_group_label>
    <arm_group_label>Oral CBD 75 BID</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Any malignant hematological disease in CR or Myelodysplastic Syndrome (MDS)&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Karnofsky Score (KS) ≥ 60%&#xD;
&#xD;
          4. HSCT-Comorbidity Index (HSCT-CI) score ≤ 3&#xD;
&#xD;
          5. No major organ dysfunction&#xD;
&#xD;
          6. Myeloablative or reduced intensity conditioning regimen&#xD;
&#xD;
          7. Matched (7/8 or 8/8) unrelated donor&#xD;
&#xD;
          8. Peripheral blood stem cell graft&#xD;
&#xD;
          9. Female subjects of childbearing potential must use a medically accepted method of&#xD;
             contraception and must agree to continue use of this method for the duration of the&#xD;
             study and for the follow-up time period. Acceptable methods of contraception include&#xD;
             abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal&#xD;
             contraceptive (oral, transdermal, implanted, and injected) in conjunction with a&#xD;
             barrier method.&#xD;
&#xD;
         10. Male subjects with partners of childbearing potential must agree to use adequate&#xD;
             contraception (barrier method or abstinence) during the study.&#xD;
&#xD;
         11. Subject's written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Malignant hematological disease other than MDS, not in CR&#xD;
&#xD;
          2. Myelofibrosis&#xD;
&#xD;
          3. Allogeneic transplantation from a matched or mismatched sibling donor&#xD;
&#xD;
          4. Cord blood transplantation&#xD;
&#xD;
          5. Positive serology for HIV&#xD;
&#xD;
          6. Serious psychiatric or psychological disorders&#xD;
&#xD;
          7. Any uncontrolled infection at time of registration&#xD;
&#xD;
          8. Active consumption of illicit drugs (such as: Crack cocaine, Heroin, Methamphetamines,&#xD;
             Cocaine, Bath Salts, Amphetamines, Methadone, Benzodiazepine, Ecstasy)&#xD;
&#xD;
          9. Use of Cannabis and/or its derivatives fourteen days prior to HSCT and for the&#xD;
             duration of study participation&#xD;
&#xD;
         10. Uncontrolled hepatitis B or active hepatitis C infection.&#xD;
&#xD;
         11. QTc&gt;450ms per Fridericia's correction and Impaired cardiac function or clinically&#xD;
             significant cardiac diseases&#xD;
&#xD;
         12. Inadequate renal function defined as measured creatinine clearance &gt; 2.0 mg/dl&#xD;
&#xD;
         13. Liver enzymes: ALT and AST &gt; 3x upper limit of normal&#xD;
&#xD;
         14. Pregnancy or breastfeeding ((positive serum β-HCG 7 days before first dose)&#xD;
&#xD;
         15. Treatment with another investigational drug, biological agent, or device within 30&#xD;
             days of first dose, or investigational cell therapy within 6 months of first dose&#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>St Vincent's Hospital Sydney - The Kinghorn Cancer Centre</name>
      <address>
        <city>Sydney</city>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Health Care - Bone Marrow Transplantation Unit</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Davidof Cancer Center, Beilinson hospital, Rabin medical center</name>
      <address>
        <city>Petach Tikva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Israel</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>February 10, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>August 31, 2021</last_update_submitted>
  <last_update_submitted_qc>August 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2021</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/NCT03840512
org study id: KAL05
nct id: NCT03840512
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A prospective, open-label, phase 2a study, to evaluate the pharmacokinetic (PK) profile,
      safety, and efficacy of multiple doses of Cannabidiol (CBD) in participants Graft-Versus-Host
      Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)
The study contains 3 cohorts of 12 participants each: All participants will be orally
      administered for 105 days with CBD at doses of 75, 150 or 300 mg (PO) BID for the prevention
      of acute GVHD (aGVHD) following allogeneic HSCT.

      In addition to the study drug, all participants will receive standard aGVHD prophylaxis
      consisting of a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of
      methotrexate (MTX). After completion of 105 treatment days, the participant will be
      followed-up until day 180.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Adverse Events (AEs) and serious adverse events (SAEs) Reporting
time frame: Up to day 180
description: All AEs will be recorded, whether considered minor or serious, drug-related or not
measure: Cumulative incidence of aGVHD at day 100 post-transplant
time frame: First 100 days after transplant
description: Cumulative Incidence of Grade B-D aGvHD
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile - AUC0-t - area under the plasma concentration-time curve (AUC0-t) up to the last quantifiable concentration (LOQ) from time of administration (t=0) up to the selected
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - λz
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life
measure: Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞
time frame: Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD
description: Pharmacokinetic (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity
measure: Cumulative incidence of aGVHD at day 180 post-transplant
time frame: Day 180 post-transplant
description: Cumulative Incidence of Grade 2-4 aGvHD
arm group label: Oral CBD 75 BID
arm group type: Experimental
arm group label: Oral CBD 150 BID
arm group type: Experimental
arm group label: Oral CBD 300 BID
arm group type: Experimental
intervention type: Drug
intervention name: CBD
description: CBD + Standard aGVHD prophylaxis calcineurin inhibitor (cyclosporine or tacrolimus) + methotrexate (MTX).
Subjects transplanted from unrelated donors or from mismatched siblings will also receive anti-T cell globulin.
arm group label: Oral CBD 150 BID
arm group label: Oral CBD 300 BID
arm group label: Oral CBD 75 BID
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Israel
responsible party type: Sponsor