A Safety and Tolerability Study of ILB® in Patients With Amyotrophic Lateral Sclerosis (ALS)

A Phase II Pilot Single-arm Safety and Tolerability Study of ILB® in Patients With Motor Neurone Disease (MND)/ Amyotrophic Lateral Sclerosis (ALS)

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.

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 Investigational Medicinal Product (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)
24. Pregnant and/or breastfeeding.