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An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)

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ClinicalTrials.gov Identifier: NCT03840512
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Kalytera Therapeutics Israel, Ltd.

Tracking Information
First Submitted Date  ICMJE February 10, 2019
First Posted Date  ICMJE February 15, 2019
Last Update Posted Date March 19, 2019
Actual Study Start Date  ICMJE June 12, 2018
Estimated Primary Completion Date October 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2019)
  • Adverse Events (AEs) and serious adverse events (SAEs) Reporting [ Time Frame: Up to day 180 ]
    All AEs will be recorded, whether considered minor or serious, drug-related or not
  • Cumulative incidence of aGVHD at day 100 post-transplant [ Time Frame: First 100 days after transplant ]
    Cumulative Incidence of Grade B-D aGvHD
  • 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 ]
    Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration
  • 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 ]
    Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration
  • 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 ]
    Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)
  • 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 ]
    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
  • 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 ]
    Pharmacokinetic (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve
  • 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 ]
    Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life
  • 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 ]
    Pharmacokinetic (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity
  • Cumulative incidence of aGVHD at day 180 post-transplant [ Time Frame: Day 180 post-transplant ]
    Cumulative Incidence of Grade 2-4 aGvHD
Original Primary Outcome Measures  ICMJE
 (submitted: February 12, 2019)
  • Adverse Events (AEs) and serious adverse events (SAEs) Reporting [ Time Frame: Up to day 180 ]
    All AEs will be recorded, whether considered minor or serious, drug-related or not
  • Cumulative incidence of aGVHD at day 100 post-transplant [ Time Frame: First 100 days after transplant ]
    Cumulative Incidence of Grade B-D aGvHD
  • 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 ]
    Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration
  • 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 ]
    Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration
  • 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 ]
    Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)
  • 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 ]
    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
  • 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 ]
    Pharmacokinetic (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve
  • 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 ]
    Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life
  • 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 ]
    Pharmacokinetic (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity
Change History Complete list of historical versions of study NCT03840512 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2019)
Cumulative incidence of aGVHD at day 180 post-transplant [ Time Frame: Day 180 post-transplant ]
Cumulative Incidence of Grade B-D aGvHD
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)
Official Title  ICMJE 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)
Brief Summary 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)
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Prevention aGVHD
Intervention  ICMJE Drug: CBD

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.

Study Arms  ICMJE
  • Experimental: Oral CBD 75 BID
    Intervention: Drug: CBD
  • Experimental: Oral CBD 150 BID
    Intervention: Drug: CBD
  • Experimental: Oral CBD 300 BID
    Intervention: Drug: CBD
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 12, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2019
Estimated Primary Completion Date October 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Any malignant hematological disease in CR or Myelodysplastic Syndrome (MDS)
  2. Age ≥ 18 years
  3. Karnofsky Score (KS) ≥ 60%
  4. HSCT-Comorbidity Index (HSCT-CI) score ≤ 3
  5. No major organ dysfunction
  6. Myeloablative or reduced intensity conditioning regimen
  7. Matched (7/8 or 8/8) unrelated donor
  8. Peripheral blood stem cell graft
  9. Female subjects of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for the follow-up time period. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
  10. Male subjects with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study.
  11. Subject's written informed consent

Exclusion Criteria:

  1. Malignant hematological disease other than MDS, not in CR
  2. Myelofibrosis
  3. Allogeneic transplantation from a matched or mismatched sibling donor
  4. Cord blood transplantation
  5. Positive serology for HIV
  6. Serious psychiatric or psychological disorders
  7. Any uncontrolled infection at time of registration
  8. Active consumption of illicit drugs (such as: Crack cocaine, Heroin, Methamphetamines, Cocaine, Bath Salts, Amphetamines, Methadone, Benzodiazepine, Ecstasy)
  9. Use of Cannabis and/or its derivatives fourteen days prior to HSCT and for the duration of study participation
  10. Uncontrolled hepatitis B or active hepatitis C infection.
  11. QTc>450ms per Fridericia's correction and Impaired cardiac function or clinically significant cardiac diseases
  12. Inadequate renal function defined as measured creatinine clearance > 2.0 mg/dl
  13. Liver enzymes: ALT and AST > 3x upper limit of normal
  14. Pregnancy or breastfeeding ((positive serum β-HCG 7 days before first dose)
  15. Treatment with another investigational drug, biological agent, or device within 30 days of first dose, or investigational cell therapy within 6 months of first dose
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sari Sagiv, Ph.D. +97252854444 sari.sagiv@kalytera.co
Listed Location Countries  ICMJE Australia,   Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03840512
Other Study ID Numbers  ICMJE KAL05
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kalytera Therapeutics Israel, Ltd.
Study Sponsor  ICMJE Kalytera Therapeutics Israel, Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kalytera Therapeutics Israel, Ltd.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP