About this trial

The goal of this placebo-controlled double-blind Phase 2 clinical trial is to test in people with early Alzheimer's 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 Alzheimer's 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 Alzheimer's 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

Fasudil
Drug
A ROCK inhibitor approved for treating vasospasms following subarachnoidal bleeding in Japan and China. Dosage: Participants will undergo a 2-week titration period at 60 mg daily before escalating to a maintenance dose of 120 mg daily.
Placebo
Drug
Placebo tablets that look identical to the fasudil tablets and will follow the same dosing schedule as participants receiving fasudil.

Treatment groups

200 Participants

are divided into 2 treatment groups

Group A: FasudilExperimental treatment 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Cognition

The primary outcome will be the FLAME computer-based working memory composite comprised of tests of working memory and episodic memory

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).

2

Brain metabolism

FDG-PET is a highly sensitive means of determining brain metabolism and has been accepted as a good proxy measure of synaptic function. Importantly, FDG-PET based measures of brain metabolism correlate well with cognitive decline in AD, better than amyloid plaques. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study suggest that FDG PET has good power to detect a 25% treatment effect over 12 months

Time frame

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

Secondary outcomes

1

Plasma levels of ptau217

This study involves the collection of blood samples, following standardized procedures. Blood markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features to fulfill inclusion criteria. The primary focus will be on examining changes in levels of plasma ptau217 and nfl, measured in pg/mL.

Time frame

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

2

Plasma levels of nfl

This study involves the collection of blood samples, following standardized procedures. Blood markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features to fulfill inclusion criteria. The primary focus will be on examining changes in levels of plasma ptau217 and nfl, measured in pg/mL.

Time frame

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

3

Levels of cerebrospinal Aβ1-40 and Aβ1-42

This study involves the collection of cerebrospinal fluid (CSF) samples, following standardized procedures. CSF markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features, measured in pg/mL.

Time frame

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

4

Levels of cerebrospinal tau and p-tau

This study involves the collection of cerebrospinal fluid (CSF) samples, following standardized procedures. CSF markers associated with Alzheimer's disease (AD) will be analyzed for typical AD features, measured in pg/mL.

Time frame

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

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

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts