Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease

Exclusion Criteria

• •A patient fulfilling any of the following criteria at screening is to be excluded from enrollment in the study:
• •1. Dependence on mechanical ventilation, defined as being unable to lay supine without it, unable to sleep without it, or continuous daytime use; presence of tracheostomy at screening; or presence of diaphragm pacing system at screening.
• •2. Treatment with a drug or device within the last 30 days that has not received regulatory approval.
• •3. Treatment within 12 months with immunomodulator or immunosuppressant agent (including but not limited to cyclophosphamide, cyclosporine, interferon-α, interferon-β-1a, rituximab, alemtuzumab, azathioprine, etanercept, infliximab, adalimumab, certolizumab, golimumab, anakinra, rilonacept, secukinumab, tocilizumab, mycophenolate mofetil, methotrexate, haematopoietic stem cell transplantation).
• •4. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections or major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks.
• •5. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
• •6. Presence of any of the following clinical conditions:
• •* Bleeding diathesis or receipt of anticoagulants within 7 days (or any other clinical condition that would, in the opinion of the investigator, place the patient at increased risk during lumbar puncture).
• •* History of one or more of the following: cardiac insufficiency (New York Heart Association \[NYHA\] III/IV), uncontrolled cardiac arrhythmias, unstable ischemic heart disease, or uncontrolled hypertension (systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 110 mmHg).
• •* History of venous thromboembolic disease within 12 months, myocardial infarction, or cerebrovascular accident.
• •* Unstable pulmonary, renal, hepatic, endocrine or hematologic disease.
• •* Autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis.
• •* Evidence of active malignant disease, malignancies diagnosed within the previous 5 years, or breast cancer diagnosed within the previous 5 years (except skin cancers other than melanoma).
• •* Human immunodeficiency virus infection or other immunodeficiency illness.
• •* Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days.
• •* Drug abuse or alcoholism within the past 12 months.
• •* Significant neuromuscular disease other than MND.
• •* Other ongoing disease that may cause neuropathy, such as toxin exposure, dietary deficiency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus erythematosus or other connective diseases, infection with HIV, hepatitis B virus (HBV), or hepatitis C (HCV), Lyme disease, multiple myeloma, Waldenström's macroglobulinemia, amyloid, and hereditary neuropathy.
• •7. Pregnancy or breastfeeding.
• •8. Deprivation of freedom by administrative or court order.