Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis (REAL)

Prior treatment

• Treatment in a clinical trial with another investigational drug within 28 days or 5 half-lives of drug before Screening 1, whichever is longer.
• Exposure at any time to any gene therapies under investigation for the treatment of ALS.
• Treatment with clenbuterol within 28 days of Screening 1, or any time between Screening 1 and enrollment.

Other illness

• Presence of other causes of neuromuscular weakness or other neurodegenerative diseases that could interfere with the objectives of the study or the safety of the subject, in the opinion of the Investigator.
• Any medical condition (including cardiovascular, hematologic, renal, hepatic, or psychiatric diseases) that in the opinion of the Investigator would disallow safe participation in the trial or interpretation of the study results.
• Known hypersensitivity to the active (fasudil) or inactive ingredients in the study drug.

Lab values

• ALT ≥ 3 x upper limit of normal (ULN) or aspartate aminotransferase (AST) ≥ 3 x ULN at Screening.
• Estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73m2 at Screening.
• On more than one of the following drug classes: long-acting nitrates, beta-blockers, or calcium channel blockers. (Note: subjects may be on one of the drug classes.)
• For Cohort 1 only: At Screening 2, neutrophil count \< 1,500/mm3, platelets \< 100,000/mm3, international normalized ratio (INR) \> 1.5 or any contraindication to or unable to tolerate lumbar puncture, including use of anticoagulant medications that cannot be withheld. For example, if a subject is taking warfarin and it cannot be withheld for lumbar puncture, this would exclude the subject from study entry.

Other

• ALSFRS-R \< 24 at Screening 1.
• Expected change in dosing of riluzole, edaravone, or PB and/or TUDCA between Screening 1 and the end of the study.
• Mechanical ventilation via tracheostomy. (Use of non-invasive ventilation e.g., continuous positive airway pressure, non-invasive bi-level positive airway pressure or non-invasive volume ventilation is not an exclusion).
• Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the opinion of the Investigator would pose a safety risk.
• Participants who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule or study evaluations.
• Systolic blood pressure \< 90 mmHg and/or diastolic blood pressure \< 60 mmHg at Screening. (Note: in the case of a systolic blood pressure \< 90 and/or diastolic blood pressure \< 60, BP measurements should be repeated after 10 minutes, and the higher reading used for Inclusion/Exclusion.)
• Known to be pregnant or lactating; or positive pregnancy test for WCBP.

• Between 18 and 75 years of age (inclusive) at Screening 1.
• Subject has had a diagnosis of probable laboratory-supported, probable, or definite ALS (as defined by El Escorial Revised ALS diagnostic criteria) by Screening 1, and no other cause of the neurological impairment has been identified.
• Average decrease in ALSFRS-R of 0.5 to 3 (inclusive) points per month, calculated using: Cohort 1 - the most recent historical ALSFRS-R score from at least 3 months prior to Screening 1. If there is no qualifying previous score, an estimated rate will be calculated using the historical date of ALS symptom onset (weakness and/or dysarthria and/or dysphagia). Cohort 2 - the historical date of ALS symptoms onset.
• Percent predicted SVC ≥ 50% at Screening 1.
• ALS symptom onset (weakness and/or dysarthria, and/or dysphagia) within 48 months of Screening 1.
• Subjects taking riluzole, edaravone, or phenylbutyrate (PB) and/or tauroursodeoxycholic acid (TUDCA) may be included if the following criteria are met at Screening 1, and there is no change in treatment between Screening 1 and Enrollment:
  • Stable dose of riluzole for at least 30 days;
  • Stable dose of edaravone for at least 3 cycles; and/or
  • Stable dose of PB and/or TUDCA for at least 90 days
  • Subjects taking any of these drugs prior to screening who intend to discontinue them before starting the study must have discontinued the drug(s) at least 28 days before Screening 1.
• Women of childbearing potential (WCBP) must agree to abstain from sex or use an adequate method of contraception for the duration of the screening period, the study drug treatment period, and for 28 days after the last dose of study drug.
• Males must agree to abstain from sex with WCBP or use an adequate method of contraception for the duration of the study drug treatment period and for 75 days after.
• Capable of providing informed consent and following trial procedures (where subject consents but is unable to sign the informed consent a legally authorized representative (LAR)/surrogate must sign on their behalf).