A Single-centre, Open Single-arm Study Where the Safety, Tolerability and Efficacy of Subcutaneously Administered ILB Will be Evaluated in Patients With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- TikoMed AB
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Change in electrocardiogram (ECG) recordings
研究概览
简要总结
This is a Phase 2a single-centre, open single-arm study in patients with Amyotrophic Lateral Sclerosis (ALS) of intermediate progression rate. Eligible subjects will be administered weekly doses of ILB. A total of 5 subcutaneous (s.c.) doses will be administered at the study clinic.
The study consists of 10 visits; One 2-part screening visit, 5 ILB administration visits, and 3 follow-up visits. Each individual patient's study participation will be 4 months, including the screening and follow-up visits. Fifteen patients are planned to be included.
The primary objective of the study is to evaluate the safety and tolerability of ILB in patients diagnosed with ALS.
ILB is a solution for subcutaneous (s.c.) injection in saline solution. The dose administered will depend on the subject's body weight at the second study visit, prior to the first ILB administration.
No formal sample size calculation has been performed for this study. The proposed sample size is considered sufficient in this early phase 2 development to provide adequate information on the patients. Categorical data will be presented as counts and percentages. Continuous data will be summarised using descriptive statistics.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to give written informed consent for participation in the study.
- •Clinical diagnosis of Amyotrophic Lateral Sclerosis (ALS).
- •Male or female patients between 18 to 80 years (inclusive).
- •Forced Vital Capacity (FVC) 65% of predicted value for gender, height and age at screening.
- •Evaluated with ALSFRS-R and Norris clinical rating scales for at least the past 4 weeks before study drug administration.
- •Exclusion criteria
- •Unable to understand information about the study or are expected not to collaborate with the study team.
- •Concurrent serious disease, other than ALS, at the discretion of the nvestigator.
- •Patients of childbearing potential not willing to use adequate double contraception with less than 1 percentage failure rate after the screening visit until the last visit.
- •Addiction to drugs or alcohol.
- •Confirmed HIV, hepatitis B or hepatitis C.
- •Known bleeding disorders or abnormal bleeding events.
- •Treatment with anticoagulant drugs warfarin and novel oral anticoagulants (NOAC) within the last 14 days prior to screening.
- •Treatment with Riluzole or Lamotrigine within the last 28 days prior to study drug administration.
- •Hypersensitivity to dextran sulfate.
- •Poor venous access.
- •Patients with clinically significant abnormal PK-INR, fibrinogen, von Willebrand factor and activated partial thromboplastin time (APTT) at screening.
排除标准
- 未提供
研究组 & 干预措施
ILB
ILB treatment
干预措施: ILB (Drug)
结局指标
主要结局
Change in electrocardiogram (ECG) recordings
时间窗: up to 3 months
Change in single 12-lead ECG (PQ/PR (ms), QRS (ms), QT (ms) and QTcF (ms)) from baseline at 3 months
Change in vital signs - body temperatue
时间窗: up to 3 months
Percent change in body temperature (degrees Celsius) from baseline at 3 months
Frequency, seriousness and intensity of Treatment-emergent Adverse Events (TEAEs)
时间窗: up to 3 months
A TEAE is any adverse event (AE) not present prior to the initiation of IMP administration or any event already present that worsens in either intensity or frequency following exposure to the IMP. AEs (including baseline events) identified using any of the following methods will be recorded: * AEs spontaneously reported by the subject * AEs observed by the Investigator or medical personnel * AEs elicited based on non-leading questions from the Investigator or medical personnel
Change in physical status
时间窗: up to 3 months
A complete physical examination according to clinical praxis will be performed, including assessment of the head, eyes, ears, nose, throat (EENT), cardiac, peripheral vascular, pulmonary, musculoskeletal, neurologic, abdominal, lymphatic and dermatological functions. According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in vital signs - blood pressure
时间窗: up to 3 months
Percent change in blood pressure (mmHg) from baseline at 3 months
Change in safety laboratory measurements - albumin
时间窗: up to 3 months
According to clinical praxis, laboratory test for albumin will be analysed. Unit of measure is g/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in safety laboratory measurements - AST, ALT, CK, alkaline phosphatase
时间窗: up to 3 months
According to clinical praxis, laboratory tests for aspartate amino-transferase (AST), alanine amino-transferase (ALT), creatine kinase (CK) and alkaline phosphatase will be analysed. Unit of measure is micro-kat/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in safety laboratory measurements - myoglobin
时间窗: up to 3 months
According to clinical praxis, laboratory test for myoglobin will be analysed. Unit of measure is micro-g/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in safety laboratory measurements - CRP
时间窗: up to 3 months
According to clinical praxis, laboratory test for C-reactive protein (CRP) will be analysed. Unit of measure is milli-g/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in hematology laboratory measurements - Hemoglobin and fibrinogen
时间窗: up to 3 months
According to clinical praxis, laboratory tests for hemoglobin (Hb) and fibrinogen will be analysed. Unit of measure is g/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in vital signs - heart rate
时间窗: up to 3 months
Percent change in heart rate (bpm, beats per minute) from baseline at 3 months
Change in safety laboratory measurements - creatinine and total bilirubin
时间窗: up to 3 months
According to clinical praxis, laboratory tests for creatinine and total bilirubin will be analysed. Unit of measure is micro-mol/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in hematology laboratory measurements - WBC, platelets, basophils, eosinophils, lymphocytes, monocytes, neutrophils
时间窗: up to 3 months
According to clinical praxis, laboratory tests for white blood cell count (WBC), platelets, basophils, eosinophils, lymphocytes, monocytes and neutrophils will be analysed. Unit of measure is 10x9/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in safety laboratory measurements - sodium, potassium, chloride, calcium, glucose (non-fasting)
时间窗: up to 3 months
According to clinical praxis, laboratory tests for sodium, potassium, chloride, calcium, glucose (non-fasting) will be analysed. Unit of measure is mmol/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in hematology laboratory measurements - Red blood cell count
时间窗: up to 3 months
According to clinical praxis, laboratory test for blood cell count (RBC) will be analysed. Unit of measure is 10x12/L According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in hematology laboratory measurements - APTT
时间窗: up to 3 months
According to clinical praxis, laboratory test for activated partial thromboplastin time (aPTT) will be analysed. Unit of measure is s According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
Change in hematology laboratory measurements - PK-INR
时间窗: up to 3 months
According to clinical praxis, laboratory test for prothrombin kinase international normalized ratio (PK-INR) will be analysed. Unitless measure According to clinical praxis each function is judged as either normal or abnormal, and either clinically significant (CS) or not clinically significant (NCS) Change from baseline at 3 months.
次要结局
- Change in functional rating with Norris rating scale(up to 3 months)
- Change in maximum plasma concentration (Cmax) of ILB(up to 1 month)
- Change in plasma concentration of hepatocyte growth factor (HGF)(up to 1 month)
- Change in functional rating with Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)(up to 3 months)
- Change in pulmonary function (FVC) from baseline(up to 3 months)
- Change in Quality of Life (QoL) assessed by visual analogue scale (VAS)(up to 1.5 months)
- Change in functional rating of autonomous and sensory symptoms(up to 3 months)
- Change in exposure (Area Under the Curve, AUC) of ILB(up to 1 month)
- Changes in APTT (effect APTT) from day of dosing (day 1)(up to 1 month)