Pilot Study to Evaluate the Efficacy and Safety of Plasma Exchange With Albutein® 5% in Patients With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Change From Baseline in Percent Predicted Forced Vital Capacity (FVC)
研究概览
简要总结
This is a pilot, phase 2, prospective, open-label, single-arm study to evaluate disease progression, forced vital capacity, and the safety and tolerability of plasma exchange (PE) using Albutein® 5% in participants with amyotrophic lateral sclerosis (ALS).
详细描述
This is a phase 2, prospective, open-label, single-arm pilot study to evaluate the efficacy and safety of PE with Albutein® 5% in participants with ALS. The planned enrollment is 10 participants who have a definite, possible, or probable diagnosis of ALS, according to the revised El Escorial criteria. Enrolled participants will be treated with PE using Albutein 5% as a replacement solution during an Intensive Treatment Phase (2 PEs per week over 3 weeks) followed by a Maintenance Treatment Phase (weekly PE for 21 weeks) for a total treatment duration of 6 months. A 6-month follow up will begin after the last PE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Subjects over 18 years of age and less than 70 years old
- •Subjects with a possible, probable-lab supported, probable, or definite diagnosis of Amyotrophic Lateral Sclerosis (ALS), according to the revised El Escorial criteria
- •Subjects having experienced their first ALS symptoms within 18 months prior to recruitment/consent
- •Forced Vital Capacity > 70%
- •Subjects must be medically suitable for study participation and willing to comply with all planned aspects of the protocol, including blood sampling, at the time of inclusion in the study.
排除标准
- •Subjects with pre-existing clinically significant lung disease not attributable to ALS
- •Subjects diagnosed with other neurodegenerative diseases or diseases associated with other motor neuron dysfunction
- •Participation in another investigational product study within one month prior to screening
- •Females who are pregnant, breastfeeding, or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/ gel/ film/ cream/ suppository, male sterilization, or true abstinence) throughout the study
- •Difficult or problematic peripheral vein access and inability to implant a central catheter which would make continuous Plasma exchange (PE) not feasible as per the visit protocol
- •Contraindication to undergo PE or subject has abnormal coagulation parameters at the discretion of the Outpatient Apheresis Unit team, including but not limited to:
- •Thrombocytopenia (platelets <100,000/ microliter [μL])
- •Fibrinogen <1.5 gram per liter (g/L)
- •International Normalized Ratio >1.5
- •Beta-blocker treatment and bradycardia <50 beats/min
- •Treatment with angiotensin-converting enzyme inhibitors which may increase the risk of allergic reactions, unless a preventive change in hypotensive treatment occurs prior to enrollment
- •History of anaphylaxis or severe systemic response to any plasma-derived albumin preparation, component of Albutein® 5%, or other blood product(s)
- •Subjects unable to interrupt treatment with acetylsalicylic acid, other oral antiplatelet, or anticoagulant
- •Renal dysfunction by elevated creatinine concentration >2 milligram per deciliter (mg/dL)
- •Presence of heart disease that contraindicates PE treatment, including ischemic cardiopathy and congestive heart failure
- •Presence of prior behavioural disorders requiring pharmacological intervention with less than 3 months of stable treatment
- •Mentally challenged subject who cannot give independent informed consent
- •Any condition that would complicate compliance with the study protocol (i.e., illness with the expectation of less than one year survival, abuse of drugs or alcohol, etc.)
结局指标
主要结局
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC)
时间窗: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
The FVC measured the volume of air that can forcibly be exhaled through a spirometer after a full inspiration. It was expressed in a percentage of actual FVC over the expected FVC result in the general population, calculated as: Percent predicted FVC (in %) = \[(observed FVC in liters)/(predicted FVC in liters)\]\*100.
Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score
时间窗: Baseline (Week 0), Weeks 4, 12, 25, 36, and 48
The ALSFRS-R includes 12 questions to assess the self-sufficiency of participants in 3 sub-domains: bulbar function (questions 1-3), fine and gross motor function (questions 4-9), and respiratory function (question 10-12). Aspects of nourishment, personal care, personal autonomy, and communication were also evaluated. Each task was graded on a five-point scale from 0 (incapable) to 4 (normal ability), with total score range from 0 (worst) to 48 (best). A positive change from Baseline indicates improvement.
次要结局
- Change From Baseline in Cognitive Function as Assessed by Behaviour Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioural Screen (ALS-CBS) Test(Baseline (Week 0), Weeks 25, and 48)
- Change From Baseline in Cognitive Function as Assessed by Symptom Status Sub-scale Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test(Baseline (Week 0), Weeks 25, and 48)
- Change From Baseline in Immune Population Profile(Baseline, Weeks 4, 12, and 48)
- Evaluation of Quality of Life Using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 (ALSA-Q40) Test Dimension Score(Weeks 25 and 48)
- Change From Baseline in Plasma Cytokine Panel Levels(Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48)
- Change From Baseline in Plasma Human Apolipoprotein Levels(Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48)
- Change From Cerebrospinal Fluid (CSF) Beta-methylamino-L-alanine (BMAA) Levels(Baseline (Week 0), Weeks 12, and 25)
- Change From Baseline in Absolute Leukocyte Count(Baseline, Weeks 4, 12, and 48)
- Change From Baseline in Cerebrospinal Fluid (CSF) Neurofilament Levels(Baseline (Week 0), Weeks 12, and 25)
- Change From Baseline in Cognitive Function as Assessed by Cognitive Screening Section Score of the Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen (ALS-CBS) Test(Baseline (Week 0), Weeks 25, and 48)
- Change From Baseline in the Motor Evoked Potential in Thenar and Hypothenar Eminence and Anterior Tibialis Muscle Determined by Electromyography (EMG)(Baseline (Week 0), Weeks 4, 12, 25, 36, and 48)
- Change From Baseline in Cerebrospinal Fluid (CSF) Human Apolipoprotein Levels(Baseline (Week 0), Weeks 12, and 25)
- Change From Baseline in CSF Cytokine Panel Levels(Baseline (Week 0), Weeks 12, and 25)
- Change From Baseline in Plasma Beta-methylamino-L-alanine (BMAA) Levels(Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48)
- Change From Baseline in Plasma Neurofilament Levels(Baseline (Week 0), before and after PE procedure at Weeks 4, 12, 24, and before PE for Weeks 36 and 48)