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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05218668




Registration number
NCT05218668
Ethics application status
Date submitted
23/11/2021
Date registered
1/02/2022

Titles & IDs
Public title
Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis (REAL)
Scientific title
A Phase 2a Open-Label Preliminary Safety, Efficacy, and Biomarker Study of WP-0512 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Secondary ID [1] 0 0
WP-0512-003
Universal Trial Number (UTN)
Trial acronym
REAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fasudil (WP-0512)
Treatment: Drugs - Fasudil (WP-0512)

Experimental: Cohort 1 - Fasudil - Oral fasudil at 180 mg/day

Experimental: Cohort 2 - Fasudil - Oral fasudil at 300 mg/day


Treatment: Drugs: Fasudil (WP-0512)
Oral fasudil up to 180 mg/day

Treatment: Drugs: Fasudil (WP-0512)
Oral fasudil up to 300 mg/day
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Through study completion, up to 164 weeks
Secondary outcome [1] 0 0
Change in the slope of the decline Revised ALS Functional Rating Scale (ALSFRS-R) during treatment vs pre-treatment lead-in
Timepoint [1] 0 0
Monthly from Screening to Week 12; Every six weeks to Week 24; Every 12 weeks to Week 154
Secondary outcome [2] 0 0
Change in the slope of the decline in percent predicted Slow Vital Capacity (SVC) during treatment vs pre-treatment lead-in
Timepoint [2] 0 0
Monthly from Screening to Week 12; Every six weeks to Week 24; Every 12 weeks to Week 154
Secondary outcome [3] 0 0
Change in the slope of the decline in muscle strength during treatment vs pre-treatment lead in
Timepoint [3] 0 0
Monthly from Screening to Week 12; Every six weeks to Week 24; Every 12 weeks to Week 154

Eligibility
Key inclusion criteria
1. Between 18 and 75 years of age (inclusive) at Screening 1.
2. 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.
3. 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.
4. Percent predicted SVC = 50% at Screening 1.
5. ALS symptom onset (weakness and/or dysarthria, and/or dysphagia) within 48 months of Screening 1.
6. 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.
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).
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. ALSFRS-R < 24 at Screening 1.
2. Expected change in dosing of riluzole, edaravone, or PB and/or TUDCA 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 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.
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.
8. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 at Screening.
9. Participants who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule or study evaluations.
10. Treatment in a clinical trial with another investigational drug within 28 days or 5 half-lives of drug before Screening 1, whichever is longer.
11. Exposure at any time to any gene therapies under investigation for the treatment of ALS.
12. Treatment with clenbuterol within 28 days of Screening 1, or any time between Screening 1 and enrollment.
13. 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.)
14. 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.)
15. Known hypersensitivity to the active (fasudil) or inactive ingredients in the study drug.
16. Known to be pregnant or lactating; or positive pregnancy test for WCBP.
17. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2028
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Calvary Health Bethlehem Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
NSW 2109 - Sydney
Recruitment postcode(s) [2] 0 0
QLD 4029 - Brisbane
Recruitment postcode(s) [3] 0 0
VIC 3195 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Woolsey Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sabrina Williams
Address 0 0
Country 0 0
Phone 0 0
+1-703-501-7820
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05218668