Inclusion Criteria:
1. Signed informed consent prior to initiation of any study-specific procedures.
2. Familial or sporadic MND defined as clinically possible, probable, or definite by Awaji-Shima Consensus Recommendations.
3. Rapidly progressive MND as defined by a decline of 3 or more points in the ALSFRS-R score during the prior 3 months.
4. First symptoms of MND within 3 years of informed consent.
5. Age between 18 and 75 years at time of informed consent.
6. Seated Forced Vital Capacity (FVC) ≥ 65% of predicted value.
7. Not taking riluzole or edaravone or on a stable dose of riluzole or edaravone for at least 3 months prior to screening visit.
8. Adequate bone marrow reserve, renal and liver function:
* absolute neutrophil count ≥ 1.5 x 109/L
* lymphocyte count \< 6.0 x 109/L
* platelet count ≥ 150 x 109/L
* hemoglobin ≥ 110 g/L
* eGFR ≥ 40 mL/min/1.73 m2
* ALT and/or AST ≤ 2x ULN
* total bilirubin ≤ 1.5x ULN
* serum albumin ≥ 28 g/L
9. Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods:
* Sexual abstinence (inactivity) for 1 month prior to screening through study completion; or
* Intrauterine device (IUD) in place for at least 3 months prior to study through study completion; or
* Stable hormonal contraception for at least 3 months prior to study through study completion; or
* Surgical sterilization (vasectomy) of male partner at least 6 months prior to study.
10. To be considered of non-childbearing potential, females should be surgically sterilized (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be post-menopausal and at least 3 years since last menses.
11. Males with female partners of childbearing potential must use contraception through study completion.
12. Able to give informed consent and able to comply with all study visits and all study procedures.
Exclusion Criteria:
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, anti-sense drugs, gene therapy, cell-depleting agents, total lymphoid irradiation). Treatment with intravenous immunoglobulin within 2 months or dimethyl fumarate within 3 months. Non-steroidal anti-inflammatory drugs are acceptable.
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. Live-attenuated vaccines within 30 days before dosing. Subjects must agree to forego live-attenuated vaccines throughout the study, including 12 weeks after the last dose of study drug.
6. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
7. Presence of any of the following clinical conditions:
* 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).
* History of human immunodeficiency virus infection or other immunodeficiency illness.
* Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days.
* History of drug abuse (not including marijuana use) 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.
8. Pregnancy or breastfeeding.
9. Deprivation of freedom by administrative or court order.
