Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis (REAL)

The study population will consist of subjects with a diagnosis of probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria; with ALS symptom onset within 48 months; and with percent predicted SVC ≥ 50% at Screening 1. Subjects must also have an average rate of decline in ALSFRS-R at Screening 1 of 0.5 to 3.0 points/month, with rate of decline calculated using historical data (either prior ALSFRS-R score or date of ALS symptom onset).

This study will be composed of a Primary Phase, with 24 weeks of open-label treatment, and an optional 42-month Extension Phase. Two cohorts will be enrolled: subjects in Cohort 1 (the primary population) will be dosed at 180 mg/day, and those in Cohort 2 will be dosed at up to 300 mg/day.

Cohort 1:

After consent, participants will undergo two screening evaluations, which will occur over the course of the 8 weeks prior to dosing with study drug. At Screening 1/Visit 1 (8 weeks before start of dosing), ALS assessments of ALSFRS-R/SVC/muscle dynamometry (HHD and hand grip) will be performed, as will safety assessments. Subjects who meet the pertinent inclusion/exclusion criteria will return for a second screening visit (Screening 2/Visit 2) approximately 4 weeks later, and ALS and safety assessment will again be conducted. Subjects who meet the pertinent Screening 2 study entry criteria will be enrolled into the study.

On Visit 3/Day 1, evaluations will be performed and dosing with study drug will begin. Dosing will be initiated at 180 mg/day. Participants will have an in-person or telephone visit at Week 1 (Visit 4) to assess for safety and drug compliance. Additional visits will occur at Weeks 4 (Visit 5), 8 (Visit 6), 12 (Visit 7), 18 (Visit 8) and 24 (Visit 9), during which ALS assessments of ALSFRS-R/SVC/HHD will be performed. For subjects who do not enter the Extension Phase, a final post-treatment follow-up visit (Visit 10) will be conducted at Week 25 (or 7±2 days after early termination).

For subjects who consent to continue in the Extension Phase, visits will occur every three months, during which ALS assessments will be done.

Blood biomarker collection will occur between enrollment and commencement of treatment, and at Week 12 (Visit 7) and Week 24 (Visit 9); during the extension phase it will occur 3 months after Week 24. CSF biomarker collection will occur between enrollment and commencement of treatment, and at Week 24 (Visit 9).