Rho Kinase Inhibitor in Amyotrophic Lateral Sclerosis (REAL) (REAL)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05218668|
Recruitment Status : Recruiting
First Posted : February 1, 2022
Last Update Posted : August 11, 2022
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: Fasudil (WP-0512)||Phase 2|
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 12-month Extension Phase.
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; after at least 10 subjects have been enrolled and safely treated at 180 mg/day for 4 weeks, subsequent subjects may be enrolled at up to 240 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 on Visit 12 and Visit 14. 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 be asked to maintain a log of adverse events, study drug compliance, and medication changes, which will be reviewed at each visit.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open label, single arm|
|Masking:||None (Open Label)|
|Masking Description:||None (Open Label)|
|Official Title:||A Phase 2a Open-Label Preliminary Safety, Efficacy, and Biomarker Study of WP-0512 in Patients With Amyotrophic Lateral Sclerosis (ALS)|
|Actual Study Start Date :||December 22, 2021|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2023|
Oral fasudil up to 240 mg/day
Drug: Fasudil (WP-0512)
Oral fasudil up to 240 mg/day
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Through study completion, up to 25 weeks ]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.
- Change in the slope of the decline in percent predicted Slow Vital Capacity (SVC) during treatment vs pre-treatment [ Time Frame: Monthly from Screening to Week 12; Every six weeks to Week 24 ]
The SVC will be measured using the study-approved portable spirometer, and assessments will be performed using a face mask. Three SVC trials are required for each testing session, however up to 5 trials may be performed if the variability between the highest and second highest SVC is 10% or greater for the first 3 trials.
The highest SVC recorded is utilized for eligibility. At least 3 measurable SVC trials must be completed to score SVC for all visits after screening. Predicted SVC values and percent predicted SVC values will be calculated using the Quanjer Global Lung Initiative equations.
- Change in the slope of the decline in muscle strength during treatment vs pre-treatment [ Time Frame: Monthly from Screening to Week 12; Every six weeks to Week 24 ]A spring-loaded device that "breaks" at pre-set forces will be used to assess readings obtained by HHD throughout the study. Grip strength dynamometry for both hands will be acquired, and the mean force in kilograms will be calculated. Measures will be obtained from each hand in triplicate.
- Change in the slope of the decline Revised ALS Functional Rating Scale (ALSFRS-R) during treatment vs pre-treatment [ Time Frame: Monthly from Screening to Week 12; Every six weeks toWeek 24] ]The ALSFRS-R is a validated rating instrument for monitoring the progression of disability inpatients with ALS and is utilized for monitoring functional change in ALS patients. The score assesses various 4 domains including: (i) bulbar function (speech, salivation, swallowing); (ii)fine motor task (handwriting, cutting food and handling utensils, with or without gastrostomy, dressing and hygiene); (iii) gross motor task (turning in bed, walking, climbing stairs); and (iv)respiratory function (dyspnea, orthopnea and respiratory insufficiency).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05218668
|Contact: Ann C Tunstall, Ph. D.||+firstname.lastname@example.org|
|Contact: Sabrina Williamsemail@example.com|
|United States, Arizona|
|Neuromuscular Research Center||Recruiting|
|Phoenix, Arizona, United States, 85028|
|Contact: Diane Newman 602-410-1675|
|Principal Investigator: Kumaraswamy Sivakumar, MD|
|United States, Colorado|
|University of Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Brianna Blume 303-724-3496|
|Principal Investigator: Laura Foster, MD|
|National Jewish Health||Recruiting|
|Denver, Colorado, United States, 80206|
|Contact: Jami Hennriksen 303-398-1233|
|Principal Investigator: Jinny Tavee, MD|
|United States, Florida|
|Lakes Research||Active, not recruiting|
|Miami Lakes, Florida, United States, 33014|
|University of South Florida||Recruiting|
|Tampa, Florida, United States, 33620|
|Contact: Jessica Shaw 813-974-9413|
|Principal Investigator: Tuan Vu, MD|
|United States, Illinois|
|Northwestern University||Not yet recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Emma Schmidt 312-503-0671|
|Principal Investigator: Senda Arjoud-Driss, MD|
|United States, Kentucky|
|University of Kentucky||Recruiting|
|Lexington, Kentucky, United States, 40506|
|Contact: Debby Taylor 617-671-9597|
|Principal Investigator: Vishakhadatta Kumaraswamy, MD|
|United States, Missouri|
|Cox Medical Center||Recruiting|
|Springfield, Missouri, United States, 65807|
|Contact: Jessica Ratcliff 417-885-3888|
|Principal Investigator: Steven Ellis, MD|
|United States, New York|
|Hospital for Special Surgery||Active, not recruiting|
|New York, New York, United States, 10021|
|Australia, New South Wales|
|Macquarie University Hospital||Recruiting|
|Sydney, New South Wales, Australia, NSW 2109|
|Contact: Richard Gan Richard.firstname.lastname@example.org|
|Principal Investigator: Dominic Rowe|
|Royal Brisbane and Women's Hospital||Recruiting|
|Brisbane, Queensland, Australia, QLD 4029|
|Contact: Susan Heggie (07) 3646 3111 email@example.com|
|Principal Investigator: Robert Henderson, MD|
|Calvary Health Bethlehem Hospital||Recruiting|
|Melbourne, Victoria, Australia, VIC 3195|
|Contact: Emma Windebank (03) 9596 2853 Emma.Windebank@calvarycare.org.au|
|Principal Investigator: Susan Mathers|