Motor Neurone Disease (MND)/Amyotrophic Lateral Sclerosis (ALS) MedDRA version: 20.0 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: ILB: 100mg/ml solution for injection and infusion
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Dextran Sodium Sulfur Salt 5, Mw 5 kDa.
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients =18 years and who have provided written informed consent to participate in the study 2. Prior to trial entry patients will have a definite diagnosis of ALS according to El Escorial Criteria. All patients will demonstrate either: ? presence of UMN (increased tone, brisk reflexes) as well as LMN (weakness, wasting and fasciculation) signs in the bulbar region and at least two of the other spinal regions (cervical, thoracic or lumbosacral) or ? presence of UMN and LMN signs in all three spinal regions (cervical, thoracic or lumbosacral) 3. Electrophysiological tests (Electromyography (EMG) / Nerve Conduction Study (NCS)) that supports the diagnosis of Motor Neurone Disease (MND) 4. Forced Vital Capacity (FVC) =50% of predicted value for gender, height and age at screening and a mean Sniff Nasal Inspiratory Pressure (SNIP) =50% of predicted value for age 5. Adequate haematological function (Hb=10g/dl), absolute neutrophil count =1.5x109/L and a platelet count =60 x109/L 6. International Normalised Ratio (INR) = 1.5, aPTT 30 – 40 seconds, PT 11-13.5 seconds 7. Patient willing and able to comply with schedule visits, treatment plan and other study procedures. 8. Patients taking Riluzole must have discontinued treatment =28 days prior to study entry (and following consent to take part in the study) 9. Women Of Child Bearing Potential (WOCBP) who agree to use highly effective means of contraception (as defined in the Heads of Medicines Agencies_Clinical Trials Facilitation Group (HMA_CTFG) guideline for the entirety of the study Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients classified as either probable or possible ALS according to El Escorial Criteria 2. Subjects in whom other causes of neuromuscular weakness have not been excluded. 3. Assisted ventilation of any type within 3 months before the screening visit or at screening 4. Patients requiring Radiologically Inserted Gastrostomy (RIG) or Percutaneous Endoscopic Gastroscopy (PEG) feeding 5. Involvement in any other interventional study involving use of another IMP or biological product within 3 months of screening 6. Any use of antioxidants, edaravone, tirasemtiv or CK-2127107 within 1 month before the screening visit. 7. Any botulinum toxin use within 3 months before the screening visit 8. Any form of stem cell or gene therapy for the treatment of amyotrophic lateral sclerosis (ALS) 9. Neuroimaging of brain and cervical spine with Magnetic Resonance Imaging (MRI) indicating compressive myelopathy as an alternate diagnosis 10. Laboratory examinations including Acetylcholine receptor (AChR) antibodies and Muscle Specific Kinase (MuSK) antibodies to exclude Bulbar onset Myasthenia gravis from Bulbar onset Motor Neurone disease as an alternate diagnosis and Antinuclear Antibodies (ANA), Anti-neutrophil cytoplasmic antibodies (ANCA), Extractable Nuclear Antigen (ENA) antibodies, Creatine Kinase (CK), electrophoresis and immunoglobulin indicating an alternate diagnosis for muscle disease like Myositis 11. Abnormal liver function defined as AST and/or ALT >3 times upper limit of normal 12. Any head trauma, intracranial or spinal surgery within 3 months of trial entry 13. Patients who have had recurrent falls will be excluded to reduce the risk of intracerebral haemorrhage with this Investigational Medicinal Product (IMP) 14. Current use of an anticoagulant e.g Warfarin, Aspirin, Clopidogrel, any novel anticoagulants (NOAC)s or low molecular weight heparin 15. Uncontrolled hypertension 16.Current or previous history of heparin-induced thrombocytopenia 17. Active peptic ulcer disease 18. Known hypersensitivity to sulphur 19. Severe liver insufficiency 20. Patients with evidence of major psychiatric illness, significant cognitive impairment or clinically evident dementia that may interfere with the patient`s ability to comply with study procedures. 21. Pulmonary illness (e.g asthma or Chronic Obstructive Pulmonary Disease (COPD) requiring regular treatment 22. Patient judged to be actively suicidal by the Investigator during 3 months before the screening visit 23. Subjects with a diagnosis of another neurodegenerative disease (e.g. Parkinson`s disease, Altzheimers disease and Frontotemporal dementia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The Primary Objective is: To determine the safety and acceptability of ILB in ALS patients ; Secondary Objective: To describe the effect of ILB on: Symptoms and quality of life ; Primary end point(s): Our primary outcome measures will inform whether the therapy is feasible in this patient group. Safety The number of SAEs and AEs will be calculated and summarised. Furhthermore, the number of patients experiencing each will be calculated. Each of these analyses will be broken down by grade, relatedness, event type (admitting event for SAEs); expectedness (SAEs only) and sequelae (SAEs only). Tolerability Measured 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 Quantity of study drug administered Total drug administered, number of administrations, number and length of interruptions, and number of discontinuations will be calculated for each patient and summarised. ; Timepoint(s) of evaluation of this end point: Interim analyses of safety outcomes and available efficacy outcomes will be presented to the relevant independent oversight committee after the sentinel patients; and periodically thereafter. Planned final analysis within 6 months of the final protocol assessment of the final | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Revised ALS Functional Rating Scale (ALSFRS-R) QOL (ALSAQ-40) Urinary p75ECD levels NfL levels Exploratory HPLC analyses of purine-pyrimidine metabolites (serum and urine) Water-soluble and Lipid-soluble Antioxidants and Vitamins (serum) Analysis of lactate (serum) HPLC analyses of primary amino acids (AA) and amino-group containing compounds (ACCG) (serum and urine) ; Timepoint(s) of evaluation of this end point: Interim analyses of safety outcomes and available efficacy outcomes will be presented to the relevant independent oversight committee (the DMC) after the sentinel patients; and periodically thereafter. Planned final analysis within 6 months of the final protocol assessment of the final patient. | — |
Countries
United Kingdom
Contacts
Public ContactMiss Claire Potter
University of Birmingham, D3B Team, Cancer Research UK Clinical Trials Unit
Outcome results
None listed