Overview

This is a Phase Ia/Ib, two-part, randomized, placebo-controlled, double-blinded, first in human(FIH) study to evaluate the safety, tolerability, PK, and PD of ADEL-Y01 in healthy participants in Part 1 and participants with MCI due to AD and mild AD in Part 2. The study includes 2 parts: Part 1 (single ascending dose [SAD] and Part 2 (multiple ascending dose [MAD]).

Eligibility

Inclusion Criteria

        Part 1: Participants are eligible to be included in the study only if all of the following
        criteria apply
          1. Provision of signed and dated, written informed consent prior to any study specific
             procedures.
          2. Healthy male and/or female (of nonchildbearing potential) participants aged 18 to 65
             years, inclusive.
          3. A body mass index (BMI) between 18 to 30 kg/m2, inclusive.
          4. Females must have a negative pregnancy test at the Screening Visit and on admission to
             the study center, must not be lactating and must be of nonchildbearing potential,
             confirmed at the Screening Visit by fulfilling 1 of the following criteria:
               -  Postmenopausal defined as amenorrhea for at least 12 months following cessation
                  of all exogenous hormonal treatments and with follicle stimulating hormone levels
                  in the laboratory defined postmenopausal range.
               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy but not tubal ligation.
          5. Male participants should be willing to use double barrier contraception ie., condoms
             and spermicide, from the day of dosing until at least 3 months after dosing with the
             investigational product.
          6. Male participant must not donate sperm from the day of dosing until at least 3 months
             after dosing with the investigational product.
          7. Medically healthy with clinically insignificant screening results (eg, laboratory
             profiles, medical history, electrocardiograms [ECGs], and physical examination) as
             judged by the Principal Investigator.
          8. Has to agree to abstain from alcohol intake 48 hours before administration of the
             study intervention and through the follow-up visit.
          9. Able to be compliant with the protocol and attend all scheduled visits.
        Part 2: Participants are eligible to be included in the study only if all of the following
        criteria apply
          1. Age between 50 and 80 years.
          2. Participants with MCI due to AD:
             i. Meet the National Institute on Aging - Alzheimer's Association (NIA-AA)6 core for
             MCI due to AD-intermediate likelihood.
             ii. Have a global clinical dementia rating (CDR) score of 0.5 and a CDR Memory Box
             score of 0.5 or greater at Screening and Baseline.
             iii. Report a history of subjective memory decline with gradual onset and slow
             progression over the last 1 year before Screening; must be corroborated by an
             informant.
             Participants with Mild AD dementia:
             iv. Meet the NIA-AA6 core for probable AD dementia. v. Have a global CDR score of 0.5
             to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline.
          3. Body weight of ≥50 kilograms and BMI between 18 and 35 kg/m2, inclusive.
          4. Mini-Mental State Examination (MMSE) score of greater than or equal to 21 and less
             than or equal to 27 at screening.
          5. Must have a positive amyloid positron emission tomography (within 12 months prior to
             screening) or CSF Abeta (42/40) ratio consistent with AD pathology.
          6. Stable dose of AD treatment (Cholinesterase inhibitors [donepezil, rivastigmine,
             galantamine] and N-methyl-D-aspartate receptor antagonist [memantine]) 3 months before
             screening visit or being untreated.
          7. Written informed consent must be obtained by participant or surrogate consenter
             (legally authorized representative).
          8. Adequate visual and auditory abilities and language skills to allow neuropsychological
             testing.
          9. Must be ambulatory.
         10. Availability of partner/caregiver who spends at least 5 hours per week with the
             participant and is willing to act as a study partner and to consent for the study.
         11. Participant on stable doses of all medications for concomitant illnesses according to
             medical history for at least 30 days prior to Visit 1 if considered relevant by the
             investigator.
         12. Sexually active males and female must be using reliable contraception methods or be
             surgically sterile.
        Exclusion Criteria
        Part 1: Participants will be excluded from the study if any of the following criteria apply
          1. History of any clinically important disease or disorder (major medical illnesses like
             cancer within 5 years, unstable angina or recent myocardial infarction, and renal
             failure) which, in the opinion of the Investigator, may either put the participant at
             risk because of participation in the study, or influence the results or the
             participant's ability to participate in the study.
          2. History or presence of gastrointestinal, hepatic, or renal disease or any other
             condition known to interfere with absorption, distribution, metabolism, or excretion
             of drugs.
          3. Any current active infections, including localized infections, or any recent history
             (within 1 week prior to study intervention administration) of active infections
             (including severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], cough or
             fever, or a history of recurrent or chronic infections).
          4. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks
             of the first administration of investigational product or planned surgical procedure
             during the study period.
          5. Any positive result at the Screening Visit for serum hepatitis B surface antigen,
             hepatitis C antibody, and human immunodeficiency virus.
          6. Blood donation within 1 month of screening or any blood donation/blood loss greater
             than 500 mL during the 3 months prior to screening.
          7. Abnormal vital signs, after 10 minute supine rest at the Screening Visit and on Day
             -1, defined as any of the following:
               -  Systolic blood pressure >140 mmHg.
               -  Diastolic blood pressure >90 mmHg.
               -  Heart rate <40 or >85 bpm.
          8. Any clinically important abnormalities in rhythm, conduction or morphology of the
             resting ECG, and any clinically important abnormalities in the 12-lead ECG as
             considered by the Investigator that may interfere with the interpretation of QTc
             interval changes.
          9. Prolonged Fridericia QT correction formula (QTcF) >450 msec at the Screening Visit and
             on Day -1.
         10. Current smokers, or those who have smoked or used nicotine products within the
             previous 1 month.
         11. History of alcohol abuse or excessive intake of alcohol defined as: an average weekly
             intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent
             to (12 g alcohol) = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5
             ounces (45 mL) of 80 proof distilled spirits.
         12. Positive screen for alcohol, drugs of abuse or cotinine (≥400 ng/mL) at the Screening
             Visit or admission to the study center or positive screen for alcohol on admission to
             the study center prior to the first administration of investigational product.
         13. History of severe allergy/hypersensitivity or ongoing clinically important
             allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity
             to any components in the investigational product.
         14. Excessive intake of caffeine containing drinks or food eg, coffee, tea, chocolate, Red
             Bull, or cola (more than 6 cups of coffee or equivalent per day) within 7 days of
             investigational product administration. One caffeine unit is contained in the
             following items: 1 (6 oz) cup of coffee, 2 (12 oz) cans of cola, 1 (12 oz) cup of tea,
             ½ (4 oz) cup of energy drink (eg, Red Bull), or 3 (1 oz) chocolate bars.
         15. Treatment with medications (including over-the-counter [OTC] medications, supplements,
             and herbal preparations such as St. John's Wort extract) within 14 days or 5
             half-lives of the drug (whichever is longer) prior to investigational product
             administration, with the exception of a limited amount of acetaminophen (up to 2 g in
             24 hours, but <1 g in 4 hours), which may be used throughout the study.
         16. Has received another new chemical entity (defined as a compound which has not been
             approved for marketing) or has participated in any other clinical study that included
             drug treatment within at least minimum 3 months of the administration of
             investigational product in this study. The period of exclusion begins 3 months after
             the final dose (or greater than 5 times half-life) or 1 month after the last visit,
             whichever is the longest.
             Note: Participants consented and screened, but not dosed in this study or a previous
             Phase 1 study, are not excluded.
         17. Ingestion of any poppy seeds within 24 hours. prior to each Drug Abuse Screening
             (Screening Visit and on Day -1 at check-in).
         18. Previous randomization to treatment in the present study.
         19. Involvement in the planning and/or conduct of the study (applies to the Sponsor,
             contract research organizations, and study center staff, etc.).
         20. Participants who are unlikely to cooperate with the requirements of the study.
         21. Judgment by the Investigator that the participant should not participate in the study
             if they have any ongoing or recent (i.e., during the screening period) minor medical
             complaints that may interfere with the interpretation of study data or are considered
             unlikely to comply with study procedures, restrictions, and requirements.
         22. Males with female partners of childbearing potential who are unwilling to use double
             barrier method of contraception for the duration of the study.
        Part 2: Participants will be excluded from the study if any of the following criteria apply
          1. History of any clinically important disease or disorder (major medical illnesses like
             cancer within 5 years, unstable angina or recent myocardial infarction, and renal
             failure) which, in the opinion of the Investigator, may either put the participant at
             risk because of participation in the study, or influence the results or the
             participant's ability to participate in the study.
          2. History or presence of gastrointestinal, hepatic, or renal disease or any other
             condition known to interfere with absorption, distribution, metabolism, or excretion
             of drugs.
          3. Any positive result at the Screening Visit for serum hepatitis B surface antigen,
             hepatitis C antibody, and human immunodeficiency virus.
          4. Any current active infections, including localized infections, or any recent history
             (within 1 week prior to study intervention administration) of active infections
             (including SARS-CoV-2, cough or fever, or a history of recurrent or chronic
             infections).
          5. Pregnant women.
          6. Participation in another clinical study within 3 months before Visit 1.
          7. Any medical or neurological condition other than AD that in the opinion of the
             investigator could be a contributing cause of the participant's dementia (eg,
             medication use, vitamin B12 deficiency, abnormal thyroid function, stroke or other
             cerebrovascular condition, diffuse Lewy body disease, head trauma).
          8. History within the past 6 months or evidence of clinically significant psychiatric
             illness (eg, major depression, schizophrenia, or bipolar affective disorder).
          9. Diagnosis of a dementia-related central nervous system disease other than AD (eg,
             Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct
             dementia, dementia with Lewy bodies, normal pressure hydrocephalus).
         10. Identification of other known cause of dementia or any other clinically significant
             contributing co-morbid pathologies at screening magnetic resonance imaging (MRI), in
             the opinion of the investigator.
         11. Participation in any other drug, biologic, device, or clinical study or treatment with
             any investigational drug or approved therapy for investigational use within 30 days
             (or 5 half-lives, whichever is longer) prior to screening, and/or participation in any
             other clinical study involving experimental medications for AD within 6 months (or 5
             halflives, whichever is longer) prior to screening.
         12. History and/or presence of autoimmune disease, if considered relevant by the
             investigator.
         13. Contraindication for MRI such as MRI-incompatible metallic endoprosthesis or MRI
             incompatible stent implantation.
         14. History of drug-induced cognitive impairment by benzodiazepines, strong sleeping aids,
             antipsychotics, narcotics, pain medicines like hydrocodone.
         15. Participation in treatment with Lecanemab or any other disease modifying anti-amyloid
             drug.
         16. History of alcohol abuse or excessive intake of alcohol defined as: an average weekly
             intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent
             to (12 g alcohol) = 5 ounces(150 mL) of wine or 12 ounces(360 mL) of beer or 1.5
             ounces (45 mL) of 80 proof distilled spirits.
         17. Positive screen for alcohol, drugs of abuse or cotinine (≥400 ng/mL) at the Screening
             Visit or admission to the study center or positive screen for alcohol on admission to
             the study center prior to the first administration of investigational product. A
             positive result for drugs of abuse is acceptable provided it can be linked a physician
             approved therapy.
         18. History of severe allergy/hypersensitivity or ongoing clinically important
             allergy/hypersensitivity to drugs likely to be used for this population, as judged by
             the Investigator or history of hypersensitivity to any components in the
             investigational product.
         19. Ingestion of any poppy seeds within 24-hour prior to each drug abuse screening
             (Screening Visit and on Day -1 at check-in).
         20. Previous randomization to treatment in the present study.
         21. Involvement in the planning and/or conduct of the study (applies to the Sponsor,
             contract research organizations, and study center staff, etc.).
         22. Participants who are unlikely to cooperate with the requirements of the study.
         23. Judgment by the Investigator that the participant should not participate in the study
             if they have any ongoing or recent (ie, during the screening period) minor medical
             complaints that may interfere with the interpretation of study data or are considered
             unlikely to comply with study procedures, restrictions, and requirements.