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)
试验速览
- 阶段
- 2 期
- 入组人数
- 36
- 试验地点
- 5
- 主要终点
- Adverse Events (AEs) and serious adverse events (SAEs) Reporting
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any malignant hematological disease in CR or Myelodysplastic Syndrome (MDS)
- •Age ≥ 18 years
- •Karnofsky Score (KS) ≥ 60%
- •HSCT-Comorbidity Index (HSCT-CI) score ≤ 3
- •No major organ dysfunction
- •Myeloablative or reduced intensity conditioning regimen
- •Matched (7/8 or 8/8) unrelated donor
- •Peripheral blood stem cell graft
- •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.
- •Male subjects with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study.
- •Subject's written informed consent
排除标准
- •Malignant hematological disease other than MDS, not in CR
- •Myelofibrosis
- •Allogeneic transplantation from a matched or mismatched sibling donor
- •Cord blood transplantation
- •Positive serology for HIV
- •Serious psychiatric or psychological disorders
- •Any uncontrolled infection at time of registration
- •Active consumption of illicit drugs (such as: Crack cocaine, Heroin, Methamphetamines, Cocaine, Bath Salts, Amphetamines, Methadone, Benzodiazepine, Ecstasy)
- •Use of Cannabis and/or its derivatives fourteen days prior to HSCT and for the duration of study participation
- •Uncontrolled hepatitis B or active hepatitis C infection.
- •QTc>450ms per Fridericia's correction and Impaired cardiac function or clinically significant cardiac diseases
- •Inadequate renal function defined as measured creatinine clearance > 2.0 mg/dl
- •Liver enzymes: ALT and AST > 3x upper limit of normal
- •Pregnancy or breastfeeding ((positive serum β-HCG 7 days before first dose)
- •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
研究组 & 干预措施
Oral CBD 75 BID
干预措施: CBD (Drug)
Oral CBD 150 BID
干预措施: CBD (Drug)
Oral CBD 300 BID
干预措施: CBD (Drug)
结局指标
主要结局
Adverse Events (AEs) and serious adverse events (SAEs) Reporting
时间窗: 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
时间窗: First 100 days after transplant
Cumulative Incidence of Grade B-D aGvHD
Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag
时间窗: 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) - Cmax
时间窗: 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
时间窗: 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) - AUC0-t
时间窗: 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
时间窗: 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
时间窗: 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-∞
时间窗: 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
时间窗: Day 180 post-transplant
Cumulative Incidence of Grade 2-4 aGvHD
次要结局
未报告次要终点