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

Full Study Summary:

The study population will consist of subjects with possible, probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria, who have ALSFRS-R declining by an average of 0.5-1.5 points per 4 weeks at the time of Screening 1/Visit 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/HHD 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, evaluations will be performed and dosing with study drug will begin. Dosing will be initiated at 180 mg/day; after at least 10 subjects have been enrolled and safely treated at 180 mg/day for 4 weeks, subsequent subjects may be enrolled at 240 mg/day. Study drug will be taken for 24 weeks. Participants will have an in-person or telephone visit at Week 1 (Visit 4) to assess for safety and drug compliance. Additional follow-up 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. A final visit (Visit 10) will be conducted at Week 25 for post-treatment follow-up evaluations.

Plasma biomarker collection will occur between enrollment and commencement of treatment, and at Week 12 (Visit 7) and Week 24 (Visit 9). CSF biomarker collection will occur between enrollment and commencement of treatment, and at Week 24 (Visit 9).

Laboratory safety assessments and adverse events will be collected at each study visit.

Subjects/caregivers will will be asked to maintain a log of study drug compliance, which will be reviewed at each visit.

• Eligibility Criteria

  Gender:

  Female, Male

  Minimum Age:

  18

  Maximum Age:

  75

  Min Vital Capacity (% predicted normal):

  50

  Time since Symptom Onset:

  >36 months

  Time since Diagnosis:

  Can participants use Riluzole?

  Yes

  
  

  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.

• Site Contact Information

  Neuromuscular Research Center
  Diane Newman / 602-410-1675
  Phoenix, Arizona 85028
  United States

  University of Colorado
  Brianna Blume / 303-724-3496
  Aurora, Colorado 80045
  United States

  National Jewish Health
  Jami Hennriksen / 303-398-1233
  Denver, Colorado 80206
  United States

  Lakes Research
  Priscila Valdiviezo / 786-362-5763
  Miami Lakes, Florida 33014
  United States

  University of South Florida
  Jessica Shaw / 813-844-8061
  Tampa, Florida 33620
  United States

  Northwestern University
  Emma Schmidt / 312-503-0671
  Chicago, Illinois 60611
  United States

  University of Kentucky
  Debby Taylor / 617-671-9597
  Lexington, Kentucky 40506
  United States

  Cox Medical Center
  Jessica Ratcliff / 417-885-3888
  Springfield, Missouri 65807
  United States

  Hospital for Special Surgery
  Shara Holzberg / 646-797-8917
  New York, New York 10021
  United States

  Macquarie University Hospital
  Richard Gan / .(JavaScript must be enabled to view this email address) / Sydney, New South Wales
  Australia

  Royal Brisbane and Women's Hospital
  Brisbane, Queensland
  Australia

  Calvary Health Bethlehem Hospital
  Melbourne, Victoria
  Australia