Open-label pilot study to assess the efficacy and safety of Cannabidiol oral solution as an adjunctive treatment for children and young adults with rare disease-associated severe epilepsy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Assess the percentage change per 28 days from the 4-week baseline period in generalized and/or focal motor-onset seizure frequency during the 24-week treatment period;
研究概览
简要总结
Demonstrate that Cannabidiol, used in addition to current anti-seizure medications, reduces the number and/or severity of motor (generalized, focal, or both) seizures in children and young adults with rare disease-associated severe epilepsy
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female aged 2-25 years as of the day of the Screening Visit;
- •Subject with rare disease-associated severe epilepsy. Subject has been certified by the National Health System as affected by a rare disease listed in https://www.malattierare.gov.it
- •Patient has severe epilepsy, with at least 4 motor (generalized, focal, or both) seizures per month during baseline period, despite 2 or more current or prior ASMs;
- •Previous treatment with at least 2 ASMs and currently taking at least 1 other ASMs or between one and four ASMs, with a stable antiseizure treatment for the previous 4 weeks (including ketogenic diet and vagal nerve stimulation);
- •Subject’s parent/caregiver has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian;
- •Subject’s parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability in the opinion of the investigator.
- •Surgical treatment for the epilepsy has failed or cannot be pursued
排除标准
- •Age <2 years
- •Inadequate supervision by parents and/or caregivers as judged by the investigator
- •Subject has been part of a clinical trial involving another investigational medicinal product in the previous six months
- •Patients with LGS, DS or TSC
- •Current or past use of recreational or medicinal cannabis, or cannabinoid-based medications, within the three months prior to screening
- •Patients with previous history of suicidal behaviour and ideation or at high suicidal risk based on clinical assessment and administration of the Columbia Suicide Severity Rating Scale (for patients 6 years of age, when appropriate otherwise, clinical judgment will be used)
- •Female patients who are pregnant and female of childbearing potential unless willing to ensure the use of a highly effective method of birth control during the study and for three months thereafter
- •Known hypersensitivity to CBD or any of the excipients in the study formulation
- •Progressive neurological disease
- •Clinically significant unstable medical conditions other than epilepsy
- •Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or affect the patient’s ability to participate in the study
- •Impaired hepatic function at screening defined as any of the following: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN) and total bilirubin (TBL) greater than 2 times the ULN
- •Subject taking more than four concurrent ASMs, corticotropins in the six months prior to screening, felbamate for less than one year prior to screening
结局指标
主要结局
Assess the percentage change per 28 days from the 4-week baseline period in generalized and/or focal motor-onset seizure frequency during the 24-week treatment period;
Assess the percentage change per 28 days from the 4-week baseline period in generalized and/or focal motor-onset seizure frequency during the 24-week treatment period;
Assess EEG improvement from baseline during treatment period in a blind senior epileptologists evaluation procedure; a score will be established for each patient, based on review and comparison of all baseline-EEG/7-weeks control-EEG and baseline-EEG/15-weeks control-EEG, with values ranging from 0 (= worsened EEG), to a maximum of 2 (= improved); 1 will be assigned if the EEG trace is unmodified
Assess EEG improvement from baseline during treatment period in a blind senior epileptologists evaluation procedure; a score will be established for each patient, based on review and comparison of all baseline-EEG/7-weeks control-EEG and baseline-EEG/15-weeks control-EEG, with values ranging from 0 (= worsened EEG), to a maximum of 2 (= improved); 1 will be assigned if the EEG trace is unmodified
次要结局
- Assess the safety and tolerability of CBD as an adjunctive therapy based on safety variables (adverse events, vital signs, body weight, physical examination, neurological examination)
- Assess pharmacokinetic interaction with concurrent ASMs (blood levels of concurrent ASMs will be taken at baseline and every 4 weeks);
- Assess the number of subjects considered treatment responders, defined as those with a ≥25%, ≥50% ≥75% reduction in motor (generalized, focal, or both) seizures from baseline;
- Assess the number of subjects who are free of motor (generalized, focal, or both) seizures;
- Assess the longest period of seizure freedom;
- Assess the number of patients experiencing a >25% worsening, −25 to +25% no change, 25–50% improvement, 50–75% improvement or >75% improvement in total seizures from baseline;
- Assess changes from baseline in number of inpatient hospitalizations due to epilepsy (6 months-period);
- Assess change in severity of seizures will be assessed using a pediatric adaptation of the Chalfont Seizure Severity Scale (Duncan & Sander, 1991);
- Assess the change from baseline to 6-months after treatment initiation in number of seizure-free days;
- Assess the changes from baseline to week 24 in the following scores: cognitive, adaptative, behavioural, functional, quality of life, caregivers and investigator impressions on global severity and improvement, sleep habits.
研究者
Clinical Trial Office
Scientific
Azienda Ospedaliero Universitaria Meyer IRCCS