NCT06247345

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

First in Human, Phase Ia/Ib Study for Safety, Tolerability, Pharmacokinetics, and Clinical Activity Evaluation of ADEL-Y01 in Healthy Participants and in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 73 (estimated)
• Sponsor: Alzheimer's Disease Expert Lab (ADEL), Inc. · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

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 \[MAD\]).

Detailed description

The current standard of care (SoC) for Alzheimer's disease (AD) is aimed at improving memory and alertness only. There is an unmet medical need for an effective clinical treatment of neurodegeneration of AD and related dementia. Adel, Inc. and Oscotec Inc. are jointly developing a novel disease modifying immunotherapy agent (ADEL-Y01) targeting tubulin associated unit (tau) protein accumulation in the brain. ADEL-Y01 is a recombinant IgG1 class type monoclonal humanized antibody that recognizes and binds to tau protein acetylated at lysine-280 (K280) thus inhibiting aggregation and propagation of tau seeds and enhancing of microglial tau clearance. Administration of ADEL-Y01 has ameliorated memory impairment, behavioral deficits, and pathology in preclinical models. This first-in-human (FIH) study will assess the single and multiple dose safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) of ADEL-Y01 in healthy adult participants and participants with mild cognitive impairment (MCI) due to AD and mild AD. Part 1 (SAD): Part 1 will recruit up to 40 healthy participants, age 18 to 65 years inclusive. Up to 5 cohorts of 8 participants (6 active and 2 placebo participants per cohort) will be enrolled with each participant receiving ADEL-Y01 or placebo. Participants will be screened within 28 days of dose administration. The participants who will meet the inclusion/exclusion criteria for the study will be enrolled into the study after providing the informed consent form (ICF). The eligible participants will be randomized on Day -1 to receive either single dose of ADEL-Y01 or placebo on Day 1. Participants will be admitted on Day -1 and remain in the clinical research unit for at least 4 days (Day 4) following completion of all schedule procedures. Participants will return to the clinical research unit for additional safety and PK assessments on 7 occasions over a total of 12-weeks. Each dose level will include 2 sentinel participants (1 active and 1 placebo) who will be dosed first and monitored by the Investigator for at least 24 hours to check safety and tolerability. Once the safety of the study intervention is ensured, remaining participants will be dosed (5 active and 1 placebo). The starting dose for the Part 1 (SAD) will be 2.5 mg/kg. Subsequent dose levels are tentatively assigned to be 7.5, 20, 50 and 100 mg/kg. Dose escalation to the next dose level(s) will not proceed until the safety and tolerability of ADEL-Y01 results over an at least 14-day assessment period have been evaluated by the Safety Review Committee (SRC). A randomization list will be prepared for each cohort separately. No participant will be dosed more than once. Part 2 (MAD): Part 2 will evaluate multiple IV doses of ADEL-Y01 administered every 2 weeks (Q2W) for 12 weeks in participants with MCI due to AD or mild AD. Thirty-three participants aged 50 to 80 years will be enrolled into 3 cohorts of 11 participants per cohort (8 active, 3 placebo) with each participant assigned to receive 6 doses of either ADEL-Y01 or placebo. Participants will be screened within 28 days of dose administration. The participants who will meet the inclusion/exclusion criteria for the study will be enrolled into the study after providing the ICF. The eligible participants will be randomized on Day -1 to receive either single dose of ADEL-Y01 or placebo on Day 1. Participants will be admitted on Day -1 and remain in the clinical research unit for at least 24 hours post infusion (Day 2) following completion of all schedule procedures. Participants will return to the clinical research unit for ADEL-Y01/placebo administration and/or additional safety and PK assessments on 12 occasions over a total of up to 22 weeks (ie, 12-weeks relative to the administration of the last dose of study intervention scheduled on Day 71). The provisional doses planned in Part 2 (MAD) are 7.5, 20, and 50 mg/kg administered every 2 weeks. The starting dose for the MAD part will be based on both safety and PK results from the Part 1 (SAD). The starting dose will be selected so that anticipated repeated-dose exposure to ADEL-Y01 (Cmax and AUC) does not exceed the exposure at the highest dose determined to be safe and well tolerated in the SAD. Depending on the Q2W ADEL-Y01 dose selected, the Part 2 (MAD) may commence prior to completion of the SAD study part. Dose escalation to the next dose level(s) will not proceed until the safety and tolerability of ADEL-Y01 over an at least 6-week assessment period (3 doses) have been evaluated by the SRC.

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
DRUG	ADEL-Y01 - healty participants	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.
DRUG	Placebo - Healthy Participants	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.
DRUG	ADEL-Y01 - MCI/AD	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.
DRUG	Placebo - MCI/AD	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.

Timeline

• Start date: 2024-02-06
• Primary completion: 2027-06-30
• Completion: 2027-07-31
• First posted: 2024-02-07
• Last updated: 2026-03-25

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study