Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

Prior treatment

• Immunosuppression due to underlying disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) or to currently receiving immunosuppressive drugs, (e.g., chemotherapy, corticosteroids) or to radiation therapy
• Stroke or myocardial infarction within 3 months prior to Screening
• Use of an investigational drug for the treatment of Amyotrophic Lateral Sclerosis in the past 30 days or 5 half-lives (if available), whichever is longer, or previous participation in a clinical study with Engensis
• Stem cell administration for investigational treatment of Amyotrophic Lateral Sclerosis or other conditions in the 6 months prior to Screening

Other illness

• Progressive or degenerative neurological disorder such as Alzheimer's disease, Parkinson's disease, vascular dementia, multiple sclerosis, and other neurological or vascular disorders felt by the Investigator to preclude participation
• Inflammatory disorder of the blood vessels (inflammatory angiopathy or vasculitis, such as Buerger's disease)
• Active infection (chronic infection or severe active infection that may compromise the Participant's wellbeing or participation in the study in the Investigator's judgment)
• Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)
• Active acute or chronic hepatitis B
• Active hepatitis C
• Active deep vein thrombosis
• Major psychiatric disorder diagnosed in the past 6 months that has not been stabilized or in the Investigator's opinion would not allow the patient to participate in the scheduled procedures

Lab values

• Evidence by physical examination, history, or laboratory evaluation of significant concomitant disease with a life expectancy of \< 6 months at Screening
• Platelet count \<100,000/µL

Age

• Recent history (\< 3 years) or presence of cancer except basal cell carcinoma or squamous cell carcinoma of the skin that was excised and has shown no evidence of recurrence for at least 1 year

Other

• Requires tracheotomy ventilation or noninvasive ventilation related to bulbar function
• International Normalized Ratio values \>2.0
• Positive human immunodeficiency virus or human T-cell lymphotrophic virus I/II test at Screening

• Clinically definite or probable Amyotrophic Lateral Sclerosis or laboratory-supported probable Amyotrophic Lateral Sclerosis as defined in the revised El Escorial/Airlie House diagnostic criteria
• The site of onset of Amyotrophic Lateral Sclerosis symptoms is a limb and experiencing symptoms of lower motor dysfunction (e.g., weakness, atrophy, cramps, poor circulation, etc.) with upper motor neuron symptoms (e.g., weakness, brisk reflexes, spasticity)
• Onset of Amyotrophic Lateral Sclerosis symptoms ≤ 4 years
• Slow Vital Capacity ≥ 50% of predicted value at Screening
• Not taking riluzole, or on a stable dose (defined as no noted toxicities) for at least 30 days prior to Screening and throughout the study
• Not taking edaravone or on a maintenance cycle for at least 30 days prior to Screening and throughout the study
• For females of childbearing potential, a negative urine pregnancy test at Screening and on Day 0
• Male Participants and their female partners must agree to use double-barrier contraception during the study or provide proof of postmenopausal state (minimum 1 year) or surgical sterility
• Male Participants must not donate sperm during the study
• Female Participants must be nonpregnant, nonlactating, and either postmenopausal for at least 1 year, or surgically sterile for at least 3 months, or agree to use double-barrier contraception from 28 days prior to randomization (Day 0) and/or their last confirmed menstrual period prior to study randomization (whichever is longer) until the end of the study
• Capable of complying and willing to comply with the requirements and restrictions in the informed consent form and this protocol
• Willing to forgo new experimental Amyotrophic Lateral Sclerosis treatments for at least 6 months following randomization