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

NCT06247345 | Terminated Phase 1 FDA Drug

• 1 other identifier: ADEL_OSCO_Y01_P101
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 6

Brief Summary

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 \[MAD\]).

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease; Dementia; Cognitive Dysfunction; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Tau MTBR; Disease Modifying Treatments; Monoclonal antibodies (mAbs)

Outcome Measures

Primary Outcomes (2)

• Part 1: Evaluation of the safety and tolerability of ADEL-Y01 via single IV injection

  The standard safety and tolerability parameters to be assessed in the study include, but are not limited to, the following: Adverse Events (AEs) Vital signs, including blood pressure, pulse rate, pulse oximetry, respiratory rate, and body temperature Digital 12-lead ECGs Clinical laboratory assessments, encompassing hematology, biochemistry, coagulation, and urinalysis Physical examinations, which will include neurological assessments.

  D-28 ~ Week 12

• Part 2: Assessment of safety and tolerability with multiple IV Administrations of ADEL-Y01 in participants with MCI due to AD or Mild AD

  The study will assess standard safety and tolerability parameters, including but not limited to the following: Adverse Events (AEs) Vital signs such as blood pressure, pulse rate, pulse oximetry, respiratory rate, and body temperature Digital 12-lead ECGs Clinical laboratory assessments, including Hematology, Biochemistry, Coagulation, and Urinalysis Physical examinations, which will encompass neurological assessments C-SSRS (Columbia-Suicide Severity Rating Scale) assessments.

  D-28 ~ Week 22

Secondary Outcomes (7)

• Part 1: Characterization of the pharmacokinetics of ADEL-Y01 following a single IV injection

  D-28 ~ Week 12

• Part 1: Assessment of the immunogenicity of ADEL-Y01 following a single IV injection

  D-28 ~ Week 12

• Part 1: Assessment of the exposure to ADEL-Y01 in CSF following a single IV injection

  D-28 ~ Week 12

• Part 2: Characterization of the pharmacokinetics of ADEL-Y01 in participants with MCI due to AD and mild AD following multiple IV injections

  D-28 ~ Week 22

• Part 2: Assessment of the immunogenicity of ADEL-Y01 in participants with MCI due to AD and mild AD following multiple IV injections

  D-28 ~ Week 22

Other Outcomes (1)

• Assessment of ADEL-Y01 Effects on Biomarkers in CSF and Plasma in Participants with MCI due to AD and Mild AD for Exploratory Objective

  D-28 ~ Week 22

Study Arms (16)

SAD Cohort 1: ADEL Y-01 antibody at a dose of 2.5mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 2.5mg/Kg in SAD cohort 1.

Drug: ADEL-Y01 - healty participants

SAD Cohort 1: Placebo at a dose of 2.5mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 2.5mg/Kg in SAD cohort 1.

Drug: Placebo - Healthy Participants

SAD Cohort 2: ADEL Y-01 antibody at a dose of 7.5mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 7.5 mg/Kg in SAD cohort 2.

Drug: ADEL-Y01 - healty participants

SAD Cohort 2: Placebo at a dose of 7.5mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 7.5mg/Kg in SAD cohort 2.

Drug: Placebo - Healthy Participants

SAD Cohort 3: ADEL Y-01 antibody at a dose of 20mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 20mg/Kg in SAD cohort 3.

Drug: ADEL-Y01 - healty participants

SAD Cohort 3: Placebo at a dose of 20mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 20mg/Kg in SAD cohort 3.

Drug: Placebo - Healthy Participants

SAD Cohort 4: ADEL Y-01 antibody at a dose of 50mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 50mg/Kg in SAD cohort 4.

Drug: ADEL-Y01 - healty participants

SAD Cohort 4: Placebo at a dose of 50mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 50mg/Kg in SAD cohort 4.

Drug: Placebo - Healthy Participants

SAD Cohort 5: ADEL Y-01 antibody at a dose of 100mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 100mg/Kg in SAD cohort 5.

Drug: ADEL-Y01 - healty participants

SAD Cohort 5: Placebo at a dose of 100mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 100mg/Kg in SAD cohort 5.

Drug: Placebo - Healthy Participants

MAD Cohort 1: ADEL Y-01 antibody at a dose of 7.5mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 7.5 mg/Kg in MAD cohort 1.

Drug: ADEL-Y01 - MCI/AD

MAD Cohort 1: Placebo at a dose of 7.5mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 7.5mg/Kg in MAD cohort 1.

Drug: Placebo - MCI/AD

MAD Cohort 2: ADEL Y-01 antibody at a dose of 20mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 20mg/Kg in MAD cohort 2.

Drug: ADEL-Y01 - MCI/AD

MAD Cohort 2: Placebo at a dose of 20mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 20mg/Kg in MAD cohort 2.

Drug: Placebo - MCI/AD

MAD Cohort 3: ADEL Y-01 antibody at a dose of 50mg/Kg

ACTIVE COMPARATOR

This arm represents the group receiving ADEL Y-01 antibody at a dose of 50mg/Kg in MAD cohort 3.

Drug: ADEL-Y01 - MCI/AD

MAD Cohort 3: Placebo at a dose of 50mg/Kg

PLACEBO COMPARATOR

This arm represents the group receiving placebo at a dose of 50mg/Kg in MAD cohort 3.

Drug: Placebo - MCI/AD

Interventions

ADEL-Y01 - healty participants DRUG

In our Part 1 clinical trial, we plan to enroll up to 40 healthy participants, aged 18 to 65, to test the safety and tolerability of ADEL-Y01. The study is divided into 5 cohorts, each with 8 participants, where 6 receive a single dose of ADEL-Y01. Screening is done 28 days prior, followed by randomization and dosing. Participants undergo initial assessments until Day 4 and additional safety and PK evaluations over 12 weeks. Starting at 2.5 mg/kg, the ADEL-Y01 dose may increase up to 100 mg/kg based on Safety Review Committee assessments, ensuring a detailed evaluation of the drug's safety.

SAD Cohort 1: ADEL Y-01 antibody at a dose of 2.5mg/Kg; SAD Cohort 2: ADEL Y-01 antibody at a dose of 7.5mg/Kg; SAD Cohort 3: ADEL Y-01 antibody at a dose of 20mg/Kg; SAD Cohort 4: ADEL Y-01 antibody at a dose of 50mg/Kg; SAD Cohort 5: ADEL Y-01 antibody at a dose of 100mg/Kg

Placebo - Healthy Participants DRUG

In Part 1 of our trial, we will enroll 2 placebo participants per cohort in up to 5 cohorts, undergoing the same protocol as those receiving ADEL-Y01 but with a placebo. They'll be part of the study from Day -1 to Day 4 for initial assessments and continue for 12 weeks for further safety and PK evaluations. This inclusion of placebo groups ensures a blinded study design for unbiased comparison of ADEL-Y01's safety and efficacy.

SAD Cohort 1: Placebo at a dose of 2.5mg/Kg; SAD Cohort 2: Placebo at a dose of 7.5mg/Kg; SAD Cohort 3: Placebo at a dose of 20mg/Kg; SAD Cohort 4: Placebo at a dose of 50mg/Kg; SAD Cohort 5: Placebo at a dose of 100mg/Kg

ADEL-Y01 - MCI/AD DRUG

In Part 2 of our trial, we assess ADEL-Y01 in 33 participants aged 50 to 80 with MCI or mild AD, administering multiple IV doses every 2 weeks for 12 weeks. Each of the 3 cohorts will have 8 participants receiving ADEL-Y01, totaling 6 doses. After initial screening and consent, participants are randomized to start treatment on Day 1, with a follow-up in the clinical research unit for safety assessments. Additional safety and PK assessments occur bi-weekly up to 22 weeks, based on the start from the last dose on Day 71. Doses are set at 7.5, 20, and 50 mg/kg, adjusted based on Part 1 results and SRC safety reviews after at least 3 doses over 6 weeks. This phase focuses on understanding ADEL-Y01's safety and efficacy in AD patients through a cautious dosing strategy.

MAD Cohort 1: ADEL Y-01 antibody at a dose of 7.5mg/Kg; MAD Cohort 2: ADEL Y-01 antibody at a dose of 20mg/Kg; MAD Cohort 3: ADEL Y-01 antibody at a dose of 50mg/Kg

Placebo - MCI/AD DRUG

In Part 2 of our clinical trial focusing on patients with MCI or mild AD, alongside the active treatment groups, we plan to include placebo groups within the 3 cohorts. Out of the 33 participants aged 50 to 80, 3 in each cohort, totaling 9 participants, will receive a placebo instead of the active drug, ADEL-Y01, administered every 2 weeks for 12 weeks. These placebo participants undergo the same screening, consent, and randomization procedures as those receiving the active drug. They are administered the placebo following the same schedule as the active groups, ensuring a controlled and blinded study environment to accurately assess ADEL-Y01's effects without bias. Placebo participants are crucial for comparing the active drug's impact on safety, tolerability, and effectiveness against a non-therapeutic intervention, maintaining the study's integrity and providing a benchmark for evaluating ADEL-Y01's true pharmacological effects on MCI or mild AD conditions.

MAD Cohort 1: Placebo at a dose of 7.5mg/Kg; MAD Cohort 2: Placebo at a dose of 20mg/Kg; MAD Cohort 3: Placebo at a dose of 50mg/Kg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1: Participants are eligible to be included in the study only if all of the following criteria apply
• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and/or female (of nonchildbearing potential) participants aged 18 to 65 years, inclusive.
• A body mass index (BMI) between 18 to 30 kg/m2, inclusive.
• 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.
• 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.
• Male participant must not donate sperm from the day of dosing until at least 3 months after dosing with the investigational product.
• Medically healthy with clinically insignificant screening results (eg, laboratory profiles, medical history, electrocardiograms \[ECGs\], and physical examination) as judged by the Principal Investigator.
• Has to agree to abstain from alcohol intake 48 hours before administration of the study intervention and through the follow-up visit.
• 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
• Age between 50 and 80 years.
• Participants with MCI due to AD:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alzheimer's Disease Expert Lab (ADEL), Inc.: lead
• Oscotec Inc.: collaborator

Study Sites (6)

CenExel ACT

Anaheim, California, 92801, United States

Location

K2 Medical Research - The Villages

Lady Lake, Florida, 32159, United States

Location

K2 Medical Research - Orlando

Maitland, Florida, 32751, United States

Location

Innovation Medical Research

Palmetto Bay, Florida, 33157, United States

Location

Accel Research - Neurostudies

Decatur, Georgia, 30030, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Cognitive Dysfunction; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Seung-Yong Yoon

  Alzheimer's Disease Expert Lab (ADEL), Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 5 cohort in Single Ascending Dose (SAD) in healthy participants and 3 cohort in Multiple Ascending Dose (MAD) in participants with mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) and mild AD

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 7, 2024
• Study Start: February 6, 2024
• Primary Completion: January 7, 2026
• Study Completion: January 7, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (6)