Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis (REAL)

NCT05218668 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: WP-0512-003
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 12

Brief Summary

A Phase 2a Open-Label Preliminary Safety, Efficacy, and Biomarker Study of WP-0512 in Patients with Amyotrophic Lateral Sclerosis (ALS)

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Fasudil

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Incidence of Adverse Events (AEs\] and Serious Adverse Events (SAEs) as assessed by clinically significant abnormal physical examination findings; changes in vital signs; 12-lead electrocardiogram (ECG); magnetic resonance imaging (MRI); and hematology, blood chemistry, liver function, and urine tests.

  Through study completion, up to 216 weeks

Secondary Outcomes (3)

• Change in the slope of the decline Revised ALS Functional Rating Scale (ALSFRS-R) during treatment vs pre-treatment lead-in

  Monthly from Screening to Week 12; Every six weeks to Week 24; Every 12 weeks to Week 206

• Change in the slope of the decline in percent predicted Slow Vital Capacity (SVC) during treatment vs pre-treatment lead-in

  Monthly from Screening to Week 12; Every six weeks to Week 24; Every 12 weeks to Week 206

• Change in the slope of the decline in muscle strength during treatment vs pre-treatment lead in

  Monthly from Screening to Week 12; Every six weeks to Week 24; Every 12 weeks to Week 206

Study Arms (2)

Cohort 1 - Fasudil

EXPERIMENTAL

Oral fasudil at 180 mg/day

Drug: Fasudil (WP-0512)

Cohort 2 - Fasudil

EXPERIMENTAL

Oral fasudil at 300 mg/day

Drug: Fasudil (WP-0512)

Interventions

Fasudil (WP-0512) DRUG

Oral fasudil up to 180 mg/day

Cohort 1 - Fasudil

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.
• Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the opinion of the Investigator would pose a safety risk.
• 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.
• Participants who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule or study evaluations.
• 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.
• 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.)
• Known hypersensitivity to the active (fasudil) or inactive ingredients in the study drug.
• Known to be pregnant or lactating; or positive pregnancy test for WCBP.
• 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.

Sponsors & Collaborators

• Woolsey Pharmaceuticals: lead

Study Sites (12)

Neuromuscular Research Center

Phoenix, Arizona, 85028, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

University of South Florida

Tampa, Florida, 33620, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

Cox Medical Center

Springfield, Missouri, 65807, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Macquarie University Hospital

Sydney, New South Wales, NSW 2109, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, QLD 4029, Australia

Location

Calvary Health Bethlehem Hospital

Melbourne, Victoria, VIC 3195, Australia

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

fasudil

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, two arms

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: February 1, 2022
• Study Start: December 22, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); AU (3)