A Phase Ia/Ib, First-in-human (FIH) Study for Safety, Tolerability, Pharmacokinetics (PK), and Clinical Activity Evaluation of ADEL-Y01

Exclusion Criteria51

• Part 1: Participants will be excluded from the study if any of the following criteria apply
• 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.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• 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).
• 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.
• Any positive result at the Screening Visit for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus.
• Blood donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening.
• 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.
• 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.
• Prolonged Fridericia QT correction formula (QTcF) \>450 msec at the Screening Visit and on Day -1.
• Current smokers, or those who have smoked or used nicotine products within the previous 1 month.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Ingestion of any poppy seeds within 24 hours. prior to each Drug Abuse Screening (Screening Visit and on Day -1 at check-in).
• Previous randomization to treatment in the present study.
• Involvement in the planning and/or conduct of the study (applies to the Sponsor, contract research organizations, and study center staff, etc.).
• Participants who are unlikely to cooperate with the requirements of the study.
• 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.
• 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
• 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.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any positive result at the Screening Visit for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus.
• 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).
• Pregnant women.
• Participation in another clinical study within 3 months before Visit 1.
• 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).
• History within the past 6 months or evidence of clinically significant psychiatric illness (eg, major depression, schizophrenia, or bipolar affective disorder).
• 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).
• 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.
• 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.
• History and/or presence of autoimmune disease, if considered relevant by the investigator.
• Contraindication for MRI such as MRI-incompatible metallic endoprosthesis or MRI incompatible stent implantation.
• History of drug-induced cognitive impairment by benzodiazepines, strong sleeping aids, antipsychotics, narcotics, pain medicines like hydrocodone.
• Participation in treatment with Lecanemab or any other disease modifying anti-amyloid drug.
• 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.
• 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.
• 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.
• Ingestion of any poppy seeds within 24-hour prior to each drug abuse screening (Screening Visit and on Day -1 at check-in).
• Previous randomization to treatment in the present study.
• Involvement in the planning and/or conduct of the study (applies to the Sponsor, contract research organizations, and study center staff, etc.).
• Participants who are unlikely to cooperate with the requirements of the study.
• 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.