Clinical trial: A Safety and Tolerability Study of ILB in Patients With Amyothrophic Lateral Sclerosis (ALS) (NCT03705390)

Eligibility 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 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)
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? Entailment