A Safety and Tolerability Study of ILB in Patients With Amyothrophic Lateral Sclerosis (ALS) (ALS)
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|ClinicalTrials.gov Identifier: NCT03705390|
Recruitment Status : Active, not recruiting
First Posted : October 15, 2018
Last Update Posted : May 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis Motor Neuron Disease||Drug: ILB||Phase 2|
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 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 (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Pilot Single-arm Safety and Tolerability Study of ILB in Patients With Motor Neurone Disease (MND)/ Amyotrophic Lateral Sclerosis (ALS)|
|Actual Study Start Date :||March 29, 2019|
|Estimated Primary Completion Date :||August 29, 2021|
|Estimated Study Completion Date :||August 29, 2021|
ILB subcutaneous injection
Administration will be weekly subcutaneous injections at a dose of 2mg/kg once per week for up to a maximum of 48 weeks
- Safety assessed by SAEs and AEs - CTCAE grading [ Time Frame: 48 weeks ]Measured by the incidence of serious adverse events (SAEs) and adverse events (AEs) using CTCAE grading v4.0. The grading is 1-5 depending on the severity of the event (5 being the most serve)
- Safety assessed by SAEs and AEs - Relatedness [ Time Frame: 48 weeks ]there is an option of 5 responses: 1 = unrelated, 2 = unlikely to be related, 3 = possibly related, 4 = probably related, 5 = definitely related
- Safety assessed by SAEs and AEs - admitted event [ Time Frame: 48 weeks ]Description of the event
- Safety assessed by SAEs and AEs - expectedness [ Time Frame: 48 weeks ]The event will be defined as expected or unexpected based on information provided in the Quick Reference Document
- Safety assessed by SAEs and AEs - sequelae [ Time Frame: 48 weeks ]outcome of event: resolved with or without sequelae
- Tolerability assessed by SAEs [ Time Frame: 48 weeks ]
Measured by the incidence of intolerable adverse events. An intolerable adverse event will satisfy all of the following criteria:
- Associated with a serious adverse event or a drug discontinuation of greater than three weeks;
- Grade 3, 4 or 5 in severity according to CTCAE version 4;
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.
- Quantity of study drug administered - total drug administered [ Time Frame: 48 weeks ]Total drug administered over the study period (measured in milligrams)
- Quantity of study drug administered - number of administrations [ Time Frame: 48 weeks ]numerical count of injections given
- Quantity of study drug administered - number and length of interruptions [ Time Frame: 48 weeks ]numerical count of injections missed and time period until next injection
- Quantity of study drug administered - number of discontinuations [ Time Frame: 48 weeks ]numerical count of patients who have discontinued treatment
- Revised Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) [ Time Frame: 48 weeks ]This is a functional rating scale, including assessments of communication, mobility, feeding, dressing and respiration. The total score range is 0 - 40; with 0 being the best outcome and 40 being the worst.
- Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) [ Time Frame: 48 weeks ]
This patient-reported outcome measures the subjective well-being of patients. It is broader than ALSFRS-R and adds assessment of emotional reactions.
There are 5 scales which are calculated and scored: physical mobility, independence, eating and drinking, communication, emotional functioning.
- Urinary p75ECD [ Time Frame: 48 weeks ]This is a biological fluid-based biomarker of ALS disease progression
- NfL in plasma [ Time Frame: 48 weeks ]This is a blood-based biomarker for neurodegeneration
- HPLC analyses of purine-pyrimidine metabolites (serum) [ Time Frame: 48 weeks ]Biomarker analysis - exploratory disease status
- HPLC analysis of fat-soluble vitamins and antioxidants (serum) [ Time Frame: 48 weeks ]Biomarker analysis - exploratory disease status
- HPLC analyses of amino acids (AA) and amino-group containing compounds (ACCG) (serum) [ Time Frame: 48 weeks ]Biomarker analysis - exploratory disease status
- Spectrophotometric analysis of lactate [ Time Frame: 48 weeks ]Biomarker analysis - exploratory disease status
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03705390
|University Hospitals Birmingham NHS Foundation Trust|
|Birmingham, West Midlands, United Kingdom, B15 2TH|
|Principal Investigator:||Venkataramanan Srinivasan, MD||University of Birmingham|