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

Inclusion Criteria:

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

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

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

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

• The participant needs to have a reliable study partner with regular contact (acombination of face-to-face visits and telephone contact is acceptable) who hassufficient interaction with the participant to provide meaningful input into ratingscales

• Age from 50 years

• Fluency in Norwegian and evidence of adequate premorbid intellectual functioning

• Capable of participating in all scheduled evaluations and complete all requiredtests

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

Exclusion Criteria:

• Significant cerebrovascular disease, as indicated by clinical history, neurologicalexamination, or on MRI (including cortical infarction or deep white matter orperiventricular 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 ≥3times Upper normal limit (ULN) at screening or baseline

• Moderate to severe hepatic impairment. Serum alanine transaminase (ALT) or aspartatetransaminase 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 autoimmunedisease.

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

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

• Recent (within 3 months) relevant medication changes. Participants must have been onstable anti-dementia (cholinesterase inhibitors or memantine) or anti-depressivemedications 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 ifthe participant has maintained stability on them for a minimum of 3 months prior tothe start of the study

• Participation in other drug trials

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

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

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