Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06362707
Status:
RECRUITING
Last Update Posted:
2024-04-15
First Post:
2024-02-02
Brief Title:
Fasudil Trial for Treatment of Early Alzheimers Disease FEAD
Sponsor:
Helse Stavanger HF
Organization:
Helse Stavanger HF
Study Overview
Official Title:
A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimers Disease FEAD
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FEAD
Brief Summary:
The goal of this placebo-controlled double-blind Phase 2 clinical trial is to test in people with early Alzheimers Disease
The main questions it aims to answer are
Does treatment with fasudil a ROCK-inhibitor lead to significant improvement in working memory based on computer-based working memory composite scores compared to placebo in individuals with early Alzheimers disease AD over 12 months
What is the effect of fasudil treatment for 12 months on other cognitive functions brain metabolism measured by Fluorodeoxyglucose Positron Emission Tomography FDG-PET and other relevant clinical functions and biomarkers in individuals with early Alzheimers disease AD
Treatment will be escalated to a maintenance dose of 120 mg total daily dose for up to 50 weeks with regular clinic visits for efficacy and safety evaluations
Assessments will include cognitive tests FDG-PET scans and biomarker analyses with follow-up by the Data and Safety Monitoring Board for ongoing safety review
The study will compare participants receiving fasudil with those receiving placebo to see if fasudil treatment leads to improvements in cognitive functions brain metabolism measured by FDG-PET
The main questions it aims to answer are
Does treatment with fasudil a ROCK-inhibitor lead to significant improvement in working memory based on computer-based working memory composite scores compared to placebo in individuals with early Alzheimers disease AD over 12 months
What is the effect of fasudil treatment for 12 months on other cognitive functions brain metabolism measured by Fluorodeoxyglucose Positron Emission Tomography FDG-PET and other relevant clinical functions and biomarkers in individuals with early Alzheimers disease AD
Treatment will be escalated to a maintenance dose of 120 mg total daily dose for up to 50 weeks with regular clinic visits for efficacy and safety evaluations
Assessments will include cognitive tests FDG-PET scans and biomarker analyses with follow-up by the Data and Safety Monitoring Board for ongoing safety review
The study will compare participants receiving fasudil with those receiving placebo to see if fasudil treatment leads to improvements in cognitive functions brain metabolism measured by FDG-PET
Detailed Description:
This is a 2-arm parallel-group 12-month randomized placebo-controlled double-blind Phase 2 trial of fasudil in up to 200 people with early AD Fasudil is a ROCK-inhibitor rho-associated protein kinase inhibitor a vasodilator that is approved for treating vasospasms following subarachnoidal bleeding in Japan and China The drug has acceptable safety and tolerability and has been shown to protect neurons and synapses in animal models of AD Eligible participants must have Stage 3-4 mild cognitive impairment MCI or mild dementia due to AD as recently defined by FDA Guidance and have shown a significant change on a validated AD biomarker eg amyloid PET scans or CSF Aβ 1-42 or blood p-tau 217 levels In addition they must have a CDR Global rating of 05 or 10 and an MRI scan within the past two years that has no findings inconsistent with AD
People who meet all inclusion criteria will be enrolled in three successive cohorts of 20 50 and 130 people respectively Participants will be randomized 11 to receive fasudil or a matching placebo All participants will undergo a 2-week titration period at a total daily dose of 60 mg 20 mg tds before being escalated to the maintenance dose of 120 mg total daily dose 40 mg tds for up to 50 additional weeks of treatment The selected dose of 120 mg per day is optimized for potential efficacy over the planned 12-month treatment while providing a reasonable margin of safety based on available clinical and nonclinical data Participants will visit the clinic for efficacy andor safety evaluations at 2-week intervals for the first month and then monthly thereafter see Table 1 Schedule of Assessments
The Data and Safety Monitoring Board DSMB will perform an unblinded review of the safety and pharmacokinetic PK data once all ongoing patients in Cohort 1 have completed at least 3 months of treatment and make recommendations to the study team that may include stopping or continuing the study with or without changes to the study procedures
The DSMB will continue to review all data available from Cohorts 1-3 for the remainder of the study at 3-monthly intervals or more frequently if warranted by emergent data and recommend any changes to the study procedures to ensure appropriate safety oversight and management of study participants through completion of the study
The primary efficacy outcome is the FLAME Factors of Longitudinal Attention Memory and Executive Function computer-based working memory composite The key secondary outcomes are based on the expression of the AD-like hypometabolic pattern on FDG-PET and additional cognitive tests from the FLAME battery including memory working memory attention and executive functions Additional secondary outcomes include CSF and blood-based AD biomarkers and clinical measures including Clinical Global Impression of Change CGIC and Clinical Dementia Rating CDR neuropsychiatric symptoms NPI instrumental activities of daily living Amsterdam IADL scale and quality of life DEMQOL Standard safety measures include monthly assessments of adverse events AEs vital signs and laboratory tests including blood and urine analyses as well as ECGs and the Columbia-Suicide Severity Rating Scale C-SSRS
People who meet all inclusion criteria will be enrolled in three successive cohorts of 20 50 and 130 people respectively Participants will be randomized 11 to receive fasudil or a matching placebo All participants will undergo a 2-week titration period at a total daily dose of 60 mg 20 mg tds before being escalated to the maintenance dose of 120 mg total daily dose 40 mg tds for up to 50 additional weeks of treatment The selected dose of 120 mg per day is optimized for potential efficacy over the planned 12-month treatment while providing a reasonable margin of safety based on available clinical and nonclinical data Participants will visit the clinic for efficacy andor safety evaluations at 2-week intervals for the first month and then monthly thereafter see Table 1 Schedule of Assessments
The Data and Safety Monitoring Board DSMB will perform an unblinded review of the safety and pharmacokinetic PK data once all ongoing patients in Cohort 1 have completed at least 3 months of treatment and make recommendations to the study team that may include stopping or continuing the study with or without changes to the study procedures
The DSMB will continue to review all data available from Cohorts 1-3 for the remainder of the study at 3-monthly intervals or more frequently if warranted by emergent data and recommend any changes to the study procedures to ensure appropriate safety oversight and management of study participants through completion of the study
The primary efficacy outcome is the FLAME Factors of Longitudinal Attention Memory and Executive Function computer-based working memory composite The key secondary outcomes are based on the expression of the AD-like hypometabolic pattern on FDG-PET and additional cognitive tests from the FLAME battery including memory working memory attention and executive functions Additional secondary outcomes include CSF and blood-based AD biomarkers and clinical measures including Clinical Global Impression of Change CGIC and Clinical Dementia Rating CDR neuropsychiatric symptoms NPI instrumental activities of daily living Amsterdam IADL scale and quality of life DEMQOL Standard safety measures include monthly assessments of adverse events AEs vital signs and laboratory tests including blood and urine analyses as well as ECGs and the Columbia-Suicide Severity Rating Scale C-SSRS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None