The Study of Safety and Preliminary Efficacy of Aleeto in Patients With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Adverse events and serious adverse events (SAEs)
研究概览
简要总结
This study is a single-center, randomized, double-blind, placebo parallel-controlled, dose-escalation clinical study. The aim of this study was to evaluate the safety, tolerability, and preliminary effect of Aleeto in adult patients with ALS, and to provide an appropriate dose for the future clinical trial.
详细描述
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which is characterized by progressive loss of number and function of upper and lower motor neurons located in the brain and spinal cord, which leads to paralysis. ALS mainly begins in the limbs and face, where about one-third of patients have difficulty in speaking, chewing, or swallowing, then progressively affecting the pharyngeal muscles, attacking the sphincter in the advanced stages of the disease, and eventually affecting the trunk and respiratory function as the disease progresses.
"Aleeto" derived from cellular exosomes, is a group of specific microenvironment protein polymers secreted by stem cells under stressed conditions, which has the advantages of selective assembly, targeted delivery, efficient repair of damaged tissues, high safety, stable chemical properties, and easy preservation. What's more, Aleeto has a strong nerve repair function.
This study is a single-center, randomized, double-blind, placebo parallel-controlled, dose-escalation clinical study, aiming to evaluate the safety, tolerability, and preliminary effect of Aleeto in adult ALS patients, and provide an appropriate dose for the future clinical trial.
In this study, we plan to enroll 24 patients, and will be randomly assigned to 4 groups. The initial dose group consists of four subjects, out of which three subjects will receive intravenous administration and intrathecal administration of 0.5μg/kg Aleeto, while one subject will receive a placebo. Fourteen subjects will be randomly assigned to the 1μg/kg and 2μg/kg dose groups to receive intrathecal administration combined with intravenous administration, with one subject in each dose group randomly receiving placebo treatment. Six subjects will be randomly assigned to the 2μg/kg dose group to receive intravenous administration only. Data are collected in face-to-face interviews at baseline and Day 14, 30, 37, 60, 67, 90, 120 follow-up visits. All patients will be examined before and after treatment, and the results will be compared.
The primary outcomes are the incidence of adverse events (AEs) and serious adverse events (SAEs), and the incidence of abnormal changes in laboratory examination indicators, vital signs, neurological physical examination, and electrocardiogram within 120 days after the treatment. The secondary outcomes included changes in immunological indicators, pharmacokinetics, ALS Functional Rating Scale-Revised (ALSFRS-R), as well as the incidence of invasive mechanical ventilation and mortality rate .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who are qualified for the clinical trial program cycle judged by well-trained physicians;
- •18 years old≤ age≤ 75 years old, males or females;
- •Forced vital capacity ≥ 80% of predicted vital capacity during the screening period;
- •The total score of the ALSFRS-R scale ≥ 30 points and ≤40 points during enrollment, and the respiratory function item ≥ 3 points;
- •Diagnosis of confirmed or probable ALS in accordance with the revised EI Escorial diagnostic criteria for amyotrophic lateral sclerosis of the World Federation of Neurology;
- •Subjects or their legal representatives clearly understand and voluntarily participate in the study and sign the informed consent form;
- •Subjects (including male subjects) are willing to have no birth plan and voluntarily take effective contraceptive measures during the entire study period and within 3 months after the end of the study, and have no plan to donate sperm or eggs.
排除标准
- •Diagnosed with familial ALS (based on family history);
- •With obvious cognitive impairment (MMSE scale: ≤19 points in the illiteracy group，≤ 22 points in the primary school group, and ≤26 points in the junior high school group (more than 8 years of education);
- •Obvious dysphagia;
- •Positive HIV test or history of positive test;
- •Positive hepatitis C virus antibody or positive test history;
- •Hepatitis B active infection (hepatitis B surface antigen positive and/or serum HBV DNA positive or serum HBV DNA > 2 × 108 IU/ml;
- •Have used other investigational drugs within 1 month or within 5 drug half-lives;
- •Diseases and deformities of the lumbar spine;
- •Have other conditions known to be associated with motor neuron dysfunction that may confuse or obscure an ALS diagnosis;
- •Other psychiatric disorders diagnosed according to DSM-V diagnostic criteria, or significant suicide intent;
- •With severe hepatic insufficiency, renal insufficiency or severe cardiac insufficiency (severe hepatic insufficiency refers to ALT value≥2.0 times the upper limit of normal value or AST value≥2.0 times the upper limit of normal value; severe renal insufficiency refers to CRE≥1.5 times the upper limit of normal value or eGFR<40mL/min/1.73m2; severe cardiac insufficiency refers to NYHA class 3-4);
- •Permanently dependent on ventilator-assisted ventilation;
- •History of alcohol and drug abuse; Edaravone users;
- •Patients who are pregnant, breast-feeding, or who are likely to become pregnant and plan to become pregnant;
- •Patients participating in other clinical trials or using other biological agents, drugs, or devices under investigation;
- •Patients who have received any vaccinations within 28 days;
- •Contraindications to MRI (eg, claustrophobia);
- •Unable to be cooperative and complete the follow-up due to other reasons.
研究组 & 干预措施
Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo
Four patients will be randomly assigned to the treatment group and the placebo group. 3 patients will receive intrathecal administration combined with intravenous administration of 0.5 μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day 1-12: Intrathecal administration of Aleeto will be conducted on Days 1, 4, 8, and 11, and intravenous administration of Aleeto on Days 2, 3, 5, 6, 9, 10, 12, and 13.
Day 31-36: Intrathecal administration of Aleeto will be conducted on Days 31 and 34, and intravenous administration of Aleeto on Days 32, 33, 35, and 36.
D61-66: Intrathecal administration of Aleeto will be conducted on Days 61 and 64, and intravenous administration of Aleeto on Days 62, 63, 65, and 66.
干预措施: Aleeto (Drug)
Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo
Four patients will be randomly assigned to the treatment group and the placebo group. 3 patients will receive intrathecal administration combined with intravenous administration of 0.5 μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day 1-12: Intrathecal administration of Aleeto will be conducted on Days 1, 4, 8, and 11, and intravenous administration of Aleeto on Days 2, 3, 5, 6, 9, 10, 12, and 13.
Day 31-36: Intrathecal administration of Aleeto will be conducted on Days 31 and 34, and intravenous administration of Aleeto on Days 32, 33, 35, and 36.
D61-66: Intrathecal administration of Aleeto will be conducted on Days 61 and 64, and intravenous administration of Aleeto on Days 62, 63, 65, and 66.
干预措施: intravenous injection (Device)
Intrathecal administration combined with intravenous administration of Aleeto(0.5μg/kg) or placebo
Four patients will be randomly assigned to the treatment group and the placebo group. 3 patients will receive intrathecal administration combined with intravenous administration of 0.5 μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day 1-12: Intrathecal administration of Aleeto will be conducted on Days 1, 4, 8, and 11, and intravenous administration of Aleeto on Days 2, 3, 5, 6, 9, 10, 12, and 13.
Day 31-36: Intrathecal administration of Aleeto will be conducted on Days 31 and 34, and intravenous administration of Aleeto on Days 32, 33, 35, and 36.
D61-66: Intrathecal administration of Aleeto will be conducted on Days 61 and 64, and intravenous administration of Aleeto on Days 62, 63, 65, and 66.
干预措施: intrathecal injection (Device)
Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo
Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 1μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13.
Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36.
D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.
干预措施: Aleeto (Drug)
Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo
Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 1μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13.
Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36.
D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.
干预措施: intravenous injection (Device)
Intrathecal administration combined with intravenous administration of Aleeto (1μg/kg) or placebo
Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 1μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13.
Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36.
D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.
干预措施: intrathecal injection (Device)
intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo
Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 2μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13.
Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36.
D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.
干预措施: Aleeto (Drug)
intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo
Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 2μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13.
Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36.
D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.
干预措施: intravenous injection (Device)
intrathecal injection and intravenous injection of Aleeto (2μg/kg) or placebo
Seven patients will be randomly assigned to the treatment group and the placebo group. 6 patients will receive intrathecal administration combined with intravenous administration of 2μg/kg Aleeto and sodium chloride, while another patient will receive the same dose of placebo.
Day1-12: Intrathecal injection of Aleeto would be given on Day 1, 4, 8, and 11, and intravenous injection of Aleeto on Day 2, 3, 5, 6, 9, 10, 12, and 13.
Day31-36: Intrathecal injection of Aleeto would be given on Day 31 and 34, and intravenous injection of Aleeto on Day 32, 33, 35, and 36.
D61-66: Intrathecal injection of Aleeto would be given on Day 61 and 64, and intravenous injection of Aleeto on Day 62, 63, 65, and 66.
干预措施: intrathecal injection (Device)
intravenous injection of Aleeto (2μg/kg)
Six patients will receive intravenous administration of 2 μg/kg Aleeto and sodium chloride.
Day1-12: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 12 days (Day 1 to 6, 8 to 13) once a day.
Day31-36: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 6 days (Day 31 to 36) once a day.
D61-66: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 6 days (Day 61 to 66) once a day.
干预措施: Aleeto (Drug)
intravenous injection of Aleeto (2μg/kg)
Six patients will receive intravenous administration of 2 μg/kg Aleeto and sodium chloride.
Day1-12: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 12 days (Day 1 to 6, 8 to 13) once a day.
Day31-36: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 6 days (Day 31 to 36) once a day.
D61-66: Patients would be given intravenous injection of Aleeto(2μg/kg) +100ml sodium chloride for 6 days (Day 61 to 66) once a day.
干预措施: intravenous injection (Device)
结局指标
主要结局
Adverse events and serious adverse events (SAEs)
时间窗: from Day 1 to Day 120
Close monitoring of patients for any physical discomfort, such as shortness of breath, rash, etc. Regular follow-up examinations of liver function, kidney function, blood routine, and other laboratory parameters should be performed. Adverse events includes abnormal liver biochemical indicators, hypersensitivity, liver failure, dyspnea, etc.
Incidence of changes in clinical laboratory examination indicators, changes in vital signs, abnormal neurological examination and abnormal electrocardiogram
时间窗: from Day 1 to Day 120
After Aleeto treatment in adult patients with ALS, monitor patients' blood routine, biochemistry, vital signs, electrocardiogram, physical examination, and other parameters.
次要结局
- Immunological markers(Day 2, Day 7, Day 14, Day 30, Day 32, Day 37, Day 60, Day 62, Day 67, Day 90, Day 120)
- Time to invasive mechanical ventilation and death(Day 2, Day 7, Day 14, Day 30, Day 32, Day 37, Day 60, Day 62, Day 67, Day 90, Day 120)
- Pharmacokinetics analysis(Day 1, Day 6, Day 13, Day 31, Day 36, Day 61, Day 66)
- ALS Functional Rating Scale-Revised(Day 120)
研究者
yilong Wang
Vice President of Beijing Tiantan Hospital
Beijing Tiantan Hospital