A Trial of Tocilizumab in ALS Subjects (TCZALS-001)

Inclusion Criteria:

• Participants with sporadic ALS (El Escorial criteria: possible, laboratory-supported probable, probable or definite)
• Capable of providing informed consent and complying with trial procedures.
• High inflammatory profile of PBMC gene expression
• Upright SVC ≥60% of predicted value for gender, height and age at Screening.
• Women must not be able to become pregnant for the duration of the study.
• First ALS symptoms occurred ≤3 years prior to Screening
• Negative tuberculosis blood test at Screening
• Not taking riluzole, or on a stable dosage for at least 30 days prior to Screening.
• Subjects medically able to undergo lumbar puncture (LP)
• Subjects must agree not to take live attenuated vaccines 30 days before Screening, throughout the duration of the trial and for 60 days following the subject's last dose of study drug
• Geographic accessibility to the study site

Exclusion Criteria:

• Prior use of Tocilizumab,cell-depleting therapies, alkylating agents, total lymphoid irradiation
• Stem cell therapies
• Dependence on mechanical ventilation as defined as being unable to lay supine without it, unable to sleep without it, or continuous daytime use
• Presence of tracheostomy at Screening
• Exposure to any other agent currently under investigation for the treatment of patients with ALS within 30 days prior to Screening
• Treatment with a prohibited medication within 30 days of the Screening Visit
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of Screening
• Presence of diaphragm pacing system at Screening.
• Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation
• History of or active diverticulitis, diverticulosis requiring antibiotic treatment, peptic ulcer disease, or GI tract perforation, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections.
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
• Presence of any of the following clinical conditions: bleeding diathesis, or any other clinical condition that would, in the opinion of the investigator, place the patient at increased risk during LP. Drug abuse or alcoholism within the past 12 months. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease, including current or prior malignancy. Rheumatic 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. Human immunodeficiency virus infection or other immunodeficient state.Uncontrolled hypertension defined as systolic blood pressure > 170 or diastolic blood pressure > 110. Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the Screening Visit
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening
• Screening ALT, AST, or total bilirubin > than 1.5 times the ULN, serum creatinine > 1.6 mg/dL in female patients and > 1.9 mg/dL in male patients (patients with serum creatinine values exceeding limits may be eligible for the study if their estimated GFR are >30), hemoglobin < 85 g/L, white blood cells < 3.0 x 109/L, absolute neutrophil count of <2000/mm3, absolute lymphocyte count < 0.5 x 109/L, platelet concentration of <100,000/mm3, negative Hep B surface antibodies
• Pregnant women or women currently breastfeeding
• No history of chicken pox infection or no history of varicella zoster vaccination