Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis

• Status: Recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Woolsey Pharmaceuticals
• Treatments: Fasudil

Criteria

Inclusion Criteria:

1. Between 18 and 75 years of age (inclusive) at Screening 1.

2. A diagnosis at Screening 1 and Screening 2 of possible, probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria.

3. Average decrease in ALSFRS-R of 0.5 to 1.5 (inclusive) points per 4 weeks [use the change between the Screening 1 ALSFRS-R and the most recent ALSFRS-R measure that is at least 12 weeks prior to Screening 1. If no prior values are available, the rate of decline can be estimated as follows: (48-value at screening)/[estimated number of months between screening and ALS symptom onset (weakness and/or dysarthria, and/or dysphagia)].

4. SVC > 50% of predicted value for gender, height, and age at Screening 1.

5. ALS symptom onset (weakness and/or dysarthria, and/or dysphagia) within 48 months of Screening 1.

6. Either no ALS treatment for 4 weeks prior to Screening 1, or stable dosing of riluzole (4 weeks on same dose) and/or at least 2 cycles of edaravone prior to Screening 1; and no change in treatment with either drug between Screening 1 and Screening 2.

7. 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.

8. 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.

9. 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).

Exclusion Criteria:

1. ALSFRS-R < 24 at Screening 1.

2. Expected change in dosing of riluzole and/or edaravone between Screening 1 and the end of the study.

3. 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.

4. 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).

5. Any severe comorbidity (including cardiovascular, hematologic, renal, hepatic, or psychiatric diseases) that in the opinion of the Investigator would disallow safe participation in the trial.

6. Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the opinion of the Investigator would pose a safety risk.

7. ALT ≥ 3 x upper limit of normal (ULN) or aspartate aminotransferase (AST) ≥ 3 x ULN at Screening 2.

8. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 at Screening 2.

9. Participants who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule or study evaluations.

10. Treatment with another investigational drug within 28 days or 5 half-lives of drug before start of study drug, whichever is longer.

11. Treatment with phenylbutyrate and tauroursodeoxycholic acid.

12. 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.)

13. Systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 60 mmHg at Screening 2. (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.)

14. Known hypersensitivity to the active (fasudil) or inactive ingredients in the study drug.

15. Known to be pregnant or lactating; or positive pregnancy test for WCBP.

16. 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 such as warfarin. Daily administration of aspirin up to 81 mg is not a contraindication, as long as the dose is held 3 days before lumbar puncture.