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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03840512




Registration number
NCT03840512
Ethics application status
Date submitted
10/02/2019
Date registered
15/02/2019
Date last updated
19/03/2019

Titles & IDs
Public title
An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)
Scientific 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)
Secondary ID [1] 0 0
KAL05
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prevention aGVHD 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CBD

Experimental: Oral CBD 75 BID -

Experimental: Oral CBD 150 BID -

Experimental: Oral CBD 300 BID -


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events (AEs) and serious adverse events (SAEs) Reporting - All AEs will be recorded, whether considered minor or serious, drug-related or not
Timepoint [1] 0 0
Up to day 180
Primary outcome [2] 0 0
Cumulative incidence of aGVHD at day 100 post-transplant - Cumulative Incidence of Grade B-D aGvHD
Timepoint [2] 0 0
First 100 days after transplant
Primary outcome [3] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax - Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration
Timepoint [3] 0 0
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
Primary outcome [4] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax - Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration
Timepoint [4] 0 0
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
Primary outcome [5] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag - Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration = Limit of Quantitation (LOQ)
Timepoint [5] 0 0
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
Primary outcome [6] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t - 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
Timepoint [6] 0 0
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
Primary outcome [7] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - ?z - Pharmacokinetic (PK) profile: ?z - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve
Timepoint [7] 0 0
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
Primary outcome [8] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2 - Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life
Timepoint [8] 0 0
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
Primary outcome [9] 0 0
Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-8 - Pharmacokinetic (PK) profile: AUC0-8 - area under the plasma concentration-time curve extrapolated to infinity
Timepoint [9] 0 0
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
Primary outcome [10] 0 0
Cumulative incidence of aGVHD at day 180 post-transplant - Cumulative Incidence of Grade 2-4 aGvHD
Timepoint [10] 0 0
Day 180 post-transplant

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 ß-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

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - The Kinghorn Cancer Centre - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Haifa
Country [2] 0 0
Israel
State/province [2] 0 0
Jerusalem
Country [3] 0 0
Israel
State/province [3] 0 0
Petach Tikva
Country [4] 0 0
Israel
State/province [4] 0 0
Tel Aviv

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Kalytera Therapeutics Israel, Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/show/NCT03840512
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sari Sagiv, Ph.D.
Address 0 0
Country 0 0
Phone 0 0
+97252854444
Fax 0 0
Email 0 0
sari.sagiv@kalytera.co
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03840512