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

2023161001

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.

2024-05-01

2025-10-01

2026-10-01

Not yet recruiting

Early phase I

200

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

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2024-04-15