This is a phase II study to determine the safety and tolerability of ILB®, a type of low molecular weight dextran sulfate, in patients with Motor Neurone Disease (MND)/ Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS) belongs to a wider group of disorders known as motor neuron diseases and mainly involves the nerve cells (neurons) in the body. Voluntary muscles produce movements like chewing, walking and talking. ALS is caused by gradual deterioration (degeneration) and death of these motor neurons. The disease is progressive, meaning the symptoms get worse over time and most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. Currently there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease (National Institute of Neurological Disorders and Stroke, Fact Sheet). The aim of this study is to explore the safety and acceptability of a type of low molecular weight dextran sulfate called ILB®. The investigators will invite 15 patients to take part from a single centre in the United Kingdom (UK). Participants will be closely monitored for any side-effects; for changes in ALS symptoms and on quality of life during and after the study. The trial period for patient participation is maximum 56 weeks (12 months), ILB® injections will be administered once weekly for up to a maximum of 48 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Administration will be weekly subcutaneous injections at a dose of 2mg/kg once per week for up to a maximum of 48 weeks
University Hospitals Birmingham NHS Foundation Trust
Birmingham, West Midlands, United Kingdom
Safety Assessed by SAEs and AEs - Measured by Incidence
Measured by the number of serious adverse events (SAEs) and adverse events (AEs) using CTCAE grading v4.0.
Time frame: From informed consent up to 30 days after last administration of trial treatment
Safety Assessed by AEs - Summarised by Grade
Grade refers to the severity of the AE as follows: Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE.
Time frame: From informed consent up to 30 days after last administration of trial treatment
Safety Assessed by AEs - Summarised by Relatedness
Relatedness categories: 1 = unrelated, 2 = unlikely to be related, 3 = possibly related, 4 = probably related, 5 = definitely related
Time frame: From informed consent up to 30 days after last administration of trial treatment
Safety Assessed by SAEs - Summarised by Admitting Event Grade
Grade refers to the severity of the admitting event as follows: Grade 1 - Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE.
Time frame: From informed consent up to 30 days after last administration of trial treatment
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Safety Assessed by SAEs - Summarised by Admitting Event Relatedness
Relatedness categories: 1 = unrelated, 2 = unlikely to be related, 3 = possibly related, 4 = probably related, 5 = definitely related
Time frame: From informed consent up to 30 days after last administration of trial treatment
Safety Assessed by SAEs - Summarised by Admitting Event Type
Description of the main event type - primary cause of admission (body system, Adverse event term and grade)
Time frame: From informed consent up to 30 days after last administration of trial treatment
Safety Assessed by SAEs - Summarised by Expectedness
Serious Adverse Events only will be defined as expected or unexpected based on information provided in the Quick Reference Document
Time frame: From informed consent up to 30 days after last administration of trial treatment
Safety Assessed by SAEs - Summarised by Sequelae
Outcome of serious adverse events only: Resolved with sequelae or Resolved without sequelae
Time frame: From informed consent up to 30 days after last administration of trial treatment
Tolerability Assessed by the Incidence of Intolerable Adverse Events
An intolerable adverse event will satisfy all of the following criteria: 1. Associated with a serious adverse event or a drug discontinuation of greater than three weeks; 2. Grade 3, 4 or 5 in severity according to CTCAE version 4; 3. In the opinion of the Investigator is i) definitely related or ii) probably related or iii) possibly related to the study drug treatment. Adverse events which are considered unrelated or probably not related will not be classed as intolerable events.
Time frame: From informed consent up to 30 days after last administration of trial treatment
Quantity of Study Drug Administered - Total Drug Administered
Total drug administered over the study period (measured in milligrams)
Time frame: From baseline to final treatment visit
Quantity of Study Drug Administered - Number of Administrations
Numerical count of the number of study drug injections given whilst on the trial
Time frame: From baseline to final treatment visit
Quantity of Study Drug Administered - Number of Interruptions
Numerical count of the number of study drug injections missed whilst on the trial
Time frame: From baseline to final treatment visit
Quantity of Study Drug Administered - Duration of Interruptions
Length of interruptions in weeks between study drug injections for those participants that experienced a treatment interruption whilst on the trial
Time frame: From baseline to final treatment visit
Quantity of Study Drug Administered - Number of Discontinuations
numerical count of patients who have discontinued study drug treatment
Time frame: From baseline to final treatment visit
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Score Change
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). This patient reported outcome measures the subjective well-being of patients. There are 5 scales which are calculated and scored: physical mobility, independence,eating and drinking, communication,emotional functioning. Each is scored between 0-100. An improved condition is represented by a decreasing sub-scale score. These sub scales are then averaged to make a summary index score. The range of the summary index is 0-100 and an improved condition is represented by decreasing summary index score. For each of the sub-scales and summary index. Interpretation is as follows: 0-19 Never or very rarely, 20-39 rarely experience problems, 40-59 sometimes experience problems,60-79 often experience, 80-100 problems (nearly) always or unable to do at all. The scale of the summary score is also 0-100 with analogous interpretation to the sub scales. An increase in score is a worse outcome.
Time frame: From baseline to final treatment visit
Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Score Change
Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 . A functional rating scale including assessments of communication, mobility, dressing and respiration. the total score range is 0-40. An improved condition is represented by decreasing sub-scale score. Interpretation is as follows: 0 being the best outcome and 40 being the worst. Minimum value is 0 and Maximum value is 40 per time-point / questionnaire completion
Time frame: From baseline to final treatment visit
Urinary p75ECD Change
Urinary p75 extracellular domain (p75ECD) is a biological fluid-based biomarker of ALS disease progression
Time frame: From baseline to final treatment visit
Pharmacokinetics (PK; Amount of Detectable Drug) of ILB® in Plasma Following Administration
This outcome measure quantifies the amount of drug detectable in the blood after administration over time
Time frame: 0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration
Pharmacokinetics (PK; Tmax) Statistics of ILB® in Plasma Following Administration
Tmax (the time the peak concentration occurred) was calculated to characterise the kinetic profile of ILB® in plasma post-administration
Time frame: 0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration
Pharmacokinetics (PK; Cmax) Statistics of ILB® in Plasma Following Administration
Cmax (peak concentration of ILB® in plasma post-administration) was calculated to characterise the kinetic profile of ILB® in plasma post-administration
Time frame: 0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration
Pharmacokinetics (PK; AUC0-last) Statistics of ILB® in Plasma Following Administration
AUC0-last (area under the curve time 0 (time of administration) to the last value above the limit of quantification) was calculated to characterise the kinetic profile of ILB® in plasma post-administration
Time frame: 0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration
Pharmacokinetics (PK; t1/2) Statistics of ILB® in Plasma Following Administration
t1/2 (terminal half-life of ILB® in plasma post-administration) was calculated to characterise the kinetic profile of ILB® in plasma post-administration
Time frame: 0.5,1,2,2.5,3,4 and 6 hours post first ILB® administration
NfL in Plasma Change
Plasma neurofilament light chain (NfL) is a blood-based biomarker for neurodegeneration
Time frame: from baseline to final treatment visit