FEAD

RecruitingPhase 2

Fasudil Trial for Treatment of Early Alzheimer's Disease (FEAD)

A Placebo Controlled Randomized Double-blind Parallel Group 12-month Trial of Fasudil for the Treatment of Early Alzheimer's Disease (FEAD)

Lead sponsor

Helse Stavanger HF

Asset

Fasudil

Listed sites

Recruiting sites

Enrollment

200

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•mild AD dementia•CDR global 0.5•Study partner/caregiver required

Primary endpoints

•Cognition•Brain metabolism

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID2023161001

NCT IDNCT06362707

Timeline

Milestones

Study first posted2024-04-12actual

Study start2024-08-01actual

Last update posted2026-05-04actual

Primary completion2028-01-01estimated

Study completion2028-01-01estimated

Assets

Drug assets

Fasudil

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age100 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Early AD, eg Stage 3 MCI or Stage 4 (mild AD dementia), as recently defined by the FDA (2018; Figure 2)

•A significant change on a validated AD amyloid or tau biomarker (as determined either by visual reading of amyloid PET scans using any of the approved ligands, or CSF Aβ 1-42 levels or blood p-tau 217 cut-offs as determined by the clinical research laboratory)

•A CDR Global rating of 0.5 or 1.0 (Morris 1993) and have an MRI scan within the past two years that has no findings inconsistent with AD

•Capacity to give informed consent based on the clinical judgement of an experienced clinician

•The participant needs to have a reliable study partner with regular contact (a combination of face-to-face visits and telephone contact is acceptable) who has sufficient interaction with the participant to provide meaningful input into rating scales

•Age from 50 years

•Fluency in Norwegian and evidence of adequate premorbid intellectual functioning

•Capable of participating in all scheduled evaluations and complete all required tests

•Female participants must be of non-childbearing potential or have a negative serum pregnancy test within 14 days of baseline assessments and agree to the use of effective birth control throughout their participation in the study

Exclusion criteria

•Significant cerebrovascular disease, as indicated by clinical history, neurological examination, or on MRI (including cortical infarction or deep white matter or periventricular white matter hyperintensities with a Fazekas scale score of 3 (Fazekas et al 1987).

•A history of cerebrovascular bleeding or severe bleeding of the digestive tract, lungs, nose or skin

•Severe renal impairment (GFR <30) or serum creatinine or urea nitrogen values ≥3 times Upper normal limit (ULN) at screening or baseline

•Moderate to severe hepatic impairment. Serum alanine transaminase (ALT) or aspartate transaminase levels ≥3 times ULN at screening or baseline

•Currently poorly controlled diabetes as indicated by HbA1c values >9

•White blood cell (WBC) values <3.5 K/μl

•History of paralytic ileus or current severe chronic constipation

•Known allergy to fasudil or established systemic inflammatory disease or autoimmune disease.

•Clinically significant hypotension defined by blood pressure values <90/60 mmHg, regardless of the individual's sitting or standing position and associated with relevant clinical symptoms (e.g., tachycardia, dizziness, syncope)

•Current clinically significant depression or other mental disorder likely to affect cognition or interfere with study participation

•Recent (within 3 months) relevant medication changes. Participants must have been on stable anti-dementia (cholinesterase inhibitors or memantine) or anti-depressive medications for at least three months before the study

•Participants using sedating drugs, if unavoidable, will be excluded from the study. However, short-acting sleep medications can be used if taken as recommended and if the participant has maintained stability on them for a minimum of 3 months prior to the start of the study

•Participation in other drug trials

•Currently ongoing life-threatening disease, such as metastatic cancer, advanced cardiovascular disease, advanced respiratory disease, terminal kidney disease, or advanced stages of infectious diseases

•Any current or past neurological disease unrelated to Alzheimer's disease with cognitive sequelae

•A Corrected QT (QTc) interval ≥ 460 milliseconds for males or ≥ 470 milliseconds for females will be considered abnormal during the ECG assessments

Endpoints (25)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Neurodegeneration biomarkers

Global cognition

Memory

Behavior / neuropsychiatric

Amyloid biomarkers

Tau biomarkers

Global cognition

1 endpoint

Primary/protocol endpoint

Brain metabolism

Time frame:The outcome will be change in FDG-PET between baseline and at 12 months.

descriptive

Memory

1 endpoint

Primary/protocol endpoint

Cognition

Time frame:The cognitive battery will be performed at baseline and every three months until last visit, supported by trial staff (up to 1 year).

descriptive

Behavior / neuropsychiatric

1 endpoint

Secondary/protocol endpoint

Columbia Suicide Severity Rating Scale (C-SSRS) (Safety assessments)

Time frame:Screening visit, month 6 and 12 months visits

descriptive

Amyloid biomarkers

1 endpoint

Secondary/protocol endpoint

Levels of cerebrospinal Aβ1-40 and Aβ1-42

Time frame:Collection of CSF samples will occur at baseline and the 12-month visit.

descriptive

Tau biomarkers

1 endpoint

Secondary/protocol endpoint

Levels of cerebrospinal tau and p-tau

Time frame:Collection of CSF samples will occur at baseline and the 12-month visit.

descriptive

Neurodegeneration biomarkers

2 endpoints

Secondary/protocol endpoint

Plasma levels of ptau217

Time frame:Collection of blood samples will occur at baseline and the 12-month visit.

Phosphorylated tau 217 (p-tau217)

descriptive

Secondary/protocol endpoint

Plasma levels of nfl

Time frame:Collection of blood samples will occur at baseline and the 12-month visit.

Phosphorylated tau 217 (p-tau217)

descriptive

Safety / tolerability / PK

18 endpoints

Secondary/protocol endpoint

Blood pressure (Safety assessments)

Time frame:Conducted at all visits throughout the 12-month duration of the study. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at screening, month 6, and month 12

descriptive

Secondary/protocol endpoint

Pulse (Safety assessments)

Time frame:Conducted at all visits throughout the 12-month duration of the study.

event count, event

Secondary/protocol endpoint

Urine testing (Safety assessments)

Time frame:Conducted at baseline and all visits throughout the 12-month duration of the study.

descriptive

Secondary/protocol endpoint

Blood urea nitrogen (BUN) (Safety assessments)