Alzheimer Disease
Conditions
Keywords
Alzheimer's Disease, ASN51
Brief summary
The main purpose of this study is to evaluate the safety, tolerability, and effect on biomarkers of disease pathophysiology and pathology, pharmacokinetics (PK), and preliminary effects on measures of clinical efficacy of multiple doses of ASN51 in adult participants with early Alzheimer's disease (AD).
Interventions
DRUGASN51
Oral capsules
DRUGPlacebo
Oral capsules
Sponsors
Asceneuron S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female age 50 to 80 years. 2. A clinical diagnosis of Alzheimer's disease (AD) at either the mild cognitive impairment or mild AD dementia stage per National Institute on Aging and the Alzheimer's Association, consistent with Stage 3 and Stage 4 in the Food and Drug Administration (FDA) draft guidance for early AD. 3. Mini-Mental State Examination score of 20 to 28 (inclusive). 4. A plasma pTau217 result consistent with the presence of amyloid pathology. 5. Must have a care partner who, in the investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities. The care partner must be literate and provide informed consent. Key
Exclusion criteria
1. Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment (e.g., current history of substance abuse, uncontrolled vitamin B12 deficiency or abnormal thyroid function, stroke or other cerebrovascular condition, normal pressure hydrocephalus, Parkinson's Disease, Lewy body dementia, cerebral amyloid angiopathy, frontotemporal dementia) or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns. 2. Non-amnestic presentation of AD as judged by the investigator. 3. Woman of childbearing potential. 4. Any prior or ongoing exposure to active or passive anti-amyloid immunotherapy, anti-tau immunotherapy, an anti-tau antisense oligonucleotide or gene therapy, or O-linked-β-N-acetylglucosaminidase (O-GlcNAcase) inhibitor. Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From first dose up to end of the study up to Week 28 | An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. |
| Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline up to Week 28 | C-SSRS is used to assess the suicidality of participants and assessment includes yes or no responses for 5 questions, each related to suicidal ideation and suicidal behavior. Numeric ratings are provided for suicidal ideation (score ranges from 1 to 5, where higher scores indicate more suicidal ideation) and suicidal behavior (score ranges from 0 to 4 where higher total scores indicate more suicidal behavior). |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Plasma pTau217 Through Week 24 | Baseline through Week 24 |
| Change From Baseline in MK-6240 Tau Positron Emission Tomography (PET) Signal Through Week 24 | Baseline through Week 24 |
| Change From Baseline in Cerebrospinal Fluid (CSF) Plasma Tau Phosphorylated at Threonine-217 (pTau217) Through Week 24 | Baseline through Week 24 |
| Maximum Plasma Concentration (Cmax) of ASN51 at Steady State | Pre-dose on Day 1 and at multiple time points post-dose up to Week 24 |
| Trough Plasma Concentration (Cmin) of ASN51 in Plasma at Steady State | Pre-dose on Day 1 and at multiple time points post-dose up to Week 24 |
| Change From Baseline in CSF Total Tau Protein Through Week 24 | Baseline through Week 24 |
Countries
United States
Participant flow
Recruitment details
A total of 123 participants with Alzheimer's disease (AD) were enrolled in the study. The study was terminated due to a strategic decision by the sponsor before randomization and hence no participants received treatment, and no data were collected or evaluated for this study.
Participants by arm
| Arm | Count |
|---|---|
| ASN51 Low Dose Participants receive low dose of ASN51 orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period or up to 36 weeks long-term extension period. | 0 |
| ASN51 High Dose Participants were to receive high dose of ASN51 orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period or up to 36 weeks long-term extension period. | 0 |
| Placebo Participants were to receive ASN51 matching placebo orally, QD for up to 24 weeks in the double-blind placebo-controlled intervention period. | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
C-SSRS is used to assess the suicidality of participants and assessment includes yes or no responses for 5 questions, each related to suicidal ideation and suicidal behavior. Numeric ratings are provided for suicidal ideation (score ranges from 1 to 5, where higher scores indicate more suicidal ideation) and suicidal behavior (score ranges from 0 to 4 where higher total scores indicate more suicidal behavior).
Time frame: Baseline up to Week 28
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Primary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Time frame: From first dose up to end of the study up to Week 28
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Secondary
Change From Baseline in Cerebrospinal Fluid (CSF) Plasma Tau Phosphorylated at Threonine-217 (pTau217) Through Week 24
Time frame: Baseline through Week 24
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Secondary
Change From Baseline in CSF Total Tau Protein Through Week 24
Time frame: Baseline through Week 24
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Secondary
Change From Baseline in MK-6240 Tau Positron Emission Tomography (PET) Signal Through Week 24
Time frame: Baseline through Week 24
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Secondary
Change From Baseline in Plasma pTau217 Through Week 24
Time frame: Baseline through Week 24
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Secondary
Maximum Plasma Concentration (Cmax) of ASN51 at Steady State
Time frame: Pre-dose on Day 1 and at multiple time points post-dose up to Week 24
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.
Secondary
Trough Plasma Concentration (Cmin) of ASN51 in Plasma at Steady State
Time frame: Pre-dose on Day 1 and at multiple time points post-dose up to Week 24
Population: The study was terminated due to a strategic decision by the sponsor. No participants received treatment, and no data were collected or evaluated for this study.