Alzheimer Disease
Conditions
Brief summary
The purpose of this study is to evaluate the effects of tricaprilin (20 g twice a day) on cognition, global function, activities of daily living, resource utilisation, safety, and tolerability, in participants with mild to moderate AD dementia. This is a randomised, double-blind, placebo-controlled, parallel-group, multi-centre design in up to 535 participants.
Interventions
DRUGTricaprilin
Each dose of IMP will be administered orally 30 minutes after completing a full meal. There is 1 g of tricaprilin per 2 ml of AC-OLE-01-VA. Participants will titrate from 5 g twice a day to 20 g twice a day, up to 40 g total daily dose of tricaprilin; 80 ml total daily dose of AC-OLE-01-VA, over the course of 2-4 weeks.
DRUGPlacebo
Each dose of IMP will be administered orally 30 minutes after completing a full meal. Participants will titrate from 5 g twice a day to 20 g twice a day, up to 40 g total daily dose of placebo; 80 ml total daily dose of placebo, over the course of 2-4 weeks.
Sponsors
Cerecin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Mini Mental State Exam (MMSE) score between 14 to 24 * Meets diagnostic clinical criteria of probable Alzheimer's disease dementia according to the NIA-AA criteria * Magnetic resonance imaging (MRI) scan less than 12 months before Baseline compatible with a diagnosis of probable AD * Plasma biomarker result supporting a diagnosis of AD before Baseline (Aβ42/40 and/or pTau217) * Confirmed APOE4 genotype result prior to Baseline * Participants taking the following cholinesterase inhibitors: donepezil, galantamine, or rivastigmine; and/or sodium oligomannate (GV-971), and/or memantine, and/or GLP-1 antagonist and/or other agents which may impact cognition are eligible for enrolment: a) If the participant has been taking such medication(s)/products for 3 months or more at Screening Visit 1; b) If the current dosage regimen is within the approved dose range; c) The daily dose has remained unchanged for at least 6 weeks prior to screening; d) If the dose is not expected to change during study participation Key
Exclusion criteria
* Has any medical/neurological/psychiatric condition, other than AD, that could explain the participant's dementia or cognitive impairment, such as but not limited to e.g., structural abnormality, traumatic brain injury, stroke, epilepsy, Parkinson's disease, alcohol-related dementia, current major depressive episode * The following GI conditions are exclusionary: a) Inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), GI bleed (upper or lower), or peptic ulcer disease; any of these conditions are exclusionary, if active in the past 5 years. Participants with remote quiescent disease, at the Investigators discretion , are not excluded; b) Participants with current or a history of (within the last 5 years) any of the following conditions are excluded: clinically significant reflux disease (e.g., Barrett's oesophagus, stricture, ulcer, haemorrhage), or severe gastroesophageal reflux disease that, in the opinion of the Investigator, is not well-controlled by medication; c) Irritable bowel syndrome, diverticular disease (e.g., diverticulosis, or diverticulitis), or chronic gastritis; any of these conditions are exclusionary if there has been an acute event within 1 year prior to Screening; d) History of gastric food intolerance, whether it be allergy or chronic oversensitivity, or a history of stomach upset reaction to a variety of foods * Current or previous treatment with any anti-amyloid or anti-Tau antibodies such as lecanemab and donanemab within 6 months prior to the day of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) total score | 26 weeks | The ADAS-Cog is a cognitive scale that assesses memory, language, orientation, and praxis with a total score range of 0 (no impairment) to 70 (severe impairment). |
| Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) | 26 weeks | The ADCS-CGIC is a clinician-rated scale of cognition, function, and behavior. Scores range from 1 (marked improvement) to 7 (marked worsening). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in a composite score of Category Fluency Test (CFT), Controlled Oral Word Association Test (COWAT), and ADAS-Cog subtests Word Recall, Word Recognition and Orientation | 26 weeks | The CFT is a cognitive test assessing a participant's semantic fluency, a measure of executive function. Participants are given 60 seconds to name as many examples of a category, with 1 point for each correct, unique response given. The COWAT is a cognitive test assessing a participant's phonemic fluency, a measure of executive function. Participants are given 60 seconds (per word) to say as many words as possible beginning e.g., with the letters F, A and S (in English, equivalents will be used for other languages), with 1 point for each original and correct word. The ADAS-Cog is a cognitive scale that assesses memory, language, orientation, and praxis with a total score range of 0 (no impairment) to 70 (severe impairment). |
| Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score | 26 weeks | The ADCS-ADL is a 23-item semi-structured interview with a caregiver and assesses 6 basic activities of daily living and 7 instrumental activities of daily living with a total score of 0 to 78. Lower scores indicate greater severity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Biomarker Analysis | 26 weeks | * Change in glial fibrillary acidic protein (GFAP) and neurofilament light chain protein (NfL) biomarker levels from Baseline to Week 26. * Change in plasma Aβ biomarker levels from Baseline to Week 26. * Change in phosphorylated tau biomarker levels from Baseline to Week 26. * Change in validated metabolomics biomarker levels from Baseline to Week 26. |
Contacts
Primary ContactStudy Director
Outcome results
None listed