A Safety and Tolerability Study of ILB in Patients With Amyothrophic 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 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.

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 Upper Motor Neuron (UMN) (increased tone, brisk reflexes) as well as Lower
Motor Neuron (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) and to exclude mimic
disorders
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, Activated Partial Thromboplastin Time
(aPTT) 30 - 40 seconds, Prothrombin Time (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 (see Appendix 8) and in combination with a
barrier contraception method (condom, diaphragm or cap) for the entirety of the study
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 neuron 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 Aspartate Transaminase (AST) and/or Alanine Transaminase (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 IMP 14. Current use of an anticoagulant e.g
Warfarin, Aspirin, Clopidogrel, any novel anticoagulants (NOAC)s or low molecular weight
subcutaneous heparin 15. Uncontrolled severe hypertension defined as systolic blood
pressure (SBP) ≥ 220 mmHg or diastolic blood pressure (DBP) ≥120 mmHg 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 patients' 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, Alzheimer's disease and Frontotemporal
dementia)