A Placebo-Controlled, Randomized Double-Blind Parallel Group 12-Month Trial of Fasudil for the Treatment of Early Alzheimer’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Stavanger HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

11 Jun 2024 → ongoing

Decision date (initial)

2024-02-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Dose response, Therapy

To assess the efficacy of fasudil 40 mg tds in preventing memory loss in people with early AD.

Secondary objectives 4

1. Assess the impact of fasudil on various cognitive measures, brain metabolism using FDG-PET, and relevant clinical features and biofluid biomarkers
2. To evaluate the safety and tolerability of fasudil 40 mg tds administered for up to 12 months in people with early AD.
3. To assess the efficacy of fasudil on brain pathology changes relevant to AD using validated fluid biomarkers
4. To evaluate additional exploratory clinical effects of fasudil 40 mg tds administered for up to 12 months in people with early AD.

Conditions and MedDRA coding

Alzheimer's disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Early AD, eg Stage 3 MCI or Stage 4 (mild AD dementia)
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).
3. A CDR Global rating of 0.5 or 1.0 and have an MRI scan within the past two years that has no findings inconsistent with AD
4. Capacity to give informed consent based on the clinical judgement of an experienced clinician
5. 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
6. Age from 50 years.
7. Fluency in Norwegian and evidence of adequate premorbid intellectual functioning
8. Capable of participating in all scheduled evaluations and complete all required tests
9. 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 16

1. 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
2. A history of cerebrovascular bleeding or severe bleeding of the digestive tract, lungs, nose or skin
3. Severe renal impairment (GFR <30) or serum creatinine or urea nitrogen values ≥3 times ULN at screening or baseline
4. Moderate to severe hepatic impairment. Serum alanine transaminase (ALT) or aspartate transaminase levels ≥3 times ULN at screening or baseline
5. Currently poorly controlled diabetes as indicated by HbA1c values >9
6. White blood cell (WBC) values <3.5 K/µl
7. History of paralytic ileus or current severe chronic constipation
8. Known allergy to fasudil or established systemic inflammatory disease or autoimmune disease.
9. 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)
10. Current clinically significant depression or other mental disorder likely to affect cognition or interfere with study participation
11. Recent (within one months) relevant medication changes. Participants must have been on stable anti-dementia (cholinesterase inhibitors or memantine) or anti-depressive medications for at least one month before the study
12. 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
13. Participation in other drug trials
14. Currently ongoing life-threatening disease, such as metastatic cancer, advanced cardiovascular disease, advanced respiratory disease, terminal kidney disease, or advanced stages of infectious diseases
15. Any current or past neurological disease unrelated to Alzheimer's disease with cognitive sequelae
16. A QTc interval ≥ 460 milliseconds for males or ≥ 470 milliseconds for females will be considered abnormal during the ECG assessments

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome will be the FLAME computer-based working memory composite, specifically the change over 12 months

Secondary endpoints 9

1. Using FLAME battery to assess speed of attention, accuracy of attention and executive function
2. Measure the extension and severity of the AD hypometabolic pattern at FDG-PET
3. Safety data will be collected through measurements of vital signs, weight, physical and neurological examination, clinical safety laboratory tests, ECG, and suicidality
4. Changes in CSF Aβ1-40, Aβ1-42, tau and p-tau and blood plasma ptau217, Nfl and other relevant markers of neurodegeneration will be assessed over 12 months.
5. Ability to perform everyday activities, and changes in functionality: Activities of daily living assessments using the Amsterdam ADL scale
6. Overall clinical condition: Clinical Global Impression of Change
7. Severity of dementia symptoms: Clinical Dementia Rating (CDR)-sum of boxes
8. Neuropsychiatric symptoms and behaviors Neuropsychiatric Inventory (NPI-Q)
9. Quality of life assessments using the DEMQOL and a short assessment of health-related costs using the EQ-5D questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Stavanger HF

Sponsor organisation

Helse Stavanger HF

Address

Gerd-Ragna Bloch Thorsens Gate 8

City

Stavanger

Postcode

4011

Country

Norway

Scientific contact point

Organisation

Helse Stavanger HF

Contact name

Dag Aarsland

Public contact point

Organisation

Helse Stavanger HF

Contact name

Dag Aarsland

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications