ADEL-Y01 for Alzheimer's Disease

Recruiting at 4 trial locations

Overseen By Minseok Kim

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Antipsychotics, Narcotics

Disqualifiers: Cancer, Renal failure, Infections, others

Compensation: Varies

Number of Visits: 20

73 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ADEL-Y01 for individuals with early stages of Alzheimer's disease, including mild cognitive impairment (MCI) and mild Alzheimer's. The main goal is to assess the safety and tolerability of this treatment for these conditions. The trial consists of two parts: one for healthy participants and another for those experiencing memory issues that have gradually worsened over the past year. It may suit someone who has noticed slow memory decline and is either on stable Alzheimer's treatment or not receiving treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

For Part 1, participants must stop taking most medications, including over-the-counter ones, 14 days before the study. For Part 2, participants can continue their Alzheimer's medications if they have been on a stable dose for 3 months before the study.

Is there any evidence suggesting that ADEL-Y01 is likely to be safe for humans?

Research shows that ADEL-Y01, a new treatment for Alzheimer's disease, is currently being tested in humans to assess its safety. As this is its first trial in people, limited information exists on its tolerance. However, the approval of similar treatments, like aducanumab, suggests potential safety. Caution remains essential with new treatments. In early animal tests, ADEL-Y01 appeared promising and did not cause major issues. However, results in animals do not always predict human outcomes. As the study progresses, more information about its safety in people will emerge. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about ADEL-Y01 for Alzheimer's disease because it represents a fresh approach by using an antibody treatment, which might offer a more targeted way to tackle the disease. Unlike traditional Alzheimer's treatments, which often focus on managing symptoms with medications like donepezil or memantine, ADEL-Y01 works by directly targeting the underlying disease mechanisms. This antibody aims to modify the progression of Alzheimer's rather than just alleviating its symptoms, offering hope for a more effective intervention.

What evidence suggests that ADEL-Y01 might be an effective treatment for Alzheimer's Disease?

Research has shown that the ADEL-Y01 antibody is designed to target and stop the progression of tauopathy, a condition linked to Alzheimer's disease. In early studies with cells and mice, ADEL-Y01 showed promise by preventing the buildup of harmful tau proteins. These proteins likely play a major role in the memory and thinking problems seen in Alzheimer's. The antibody specifically targets a changed form of tau, making it a hopeful option for slowing or preventing the disease's progression. Although human studies have provided limited information so far, early results in animal studies are encouraging. Participants in this trial will receive different doses of ADEL-Y01 or a placebo to further evaluate its effectiveness and safety. ^{1 2 6 7 8}

Who Is on the Research Team?

Seung-Yong Yoon

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-65 with a BMI of 18-30 kg/m2, who are not able to have children. Women must be postmenopausal or surgically sterile, and men must agree to use double contraception. Participants should be in good health as determined by the investigator and cannot drink alcohol before dosing.

Inclusion Criteria

Must have a positive amyloid positron emission tomography (within 12 months prior to screening) or CSF Abeta (42/40) ratio consistent with AD pathology

I am a male willing to use condoms and spermicide for 3 months after treatment.

Written informed consent must be obtained by participant or surrogate consenter

Exclusion Criteria

I am a male unwilling to use two forms of birth control.

Ingestion of poppy seeds within 24 hours prior to each Drug Abuse Screening

Abnormal vital signs, abnormal ECG findings, or prolonged QTcF

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment Part 1 (SAD)

Single ascending dose administration of ADEL-Y01 or placebo to healthy participants

12 weeks

8 visits (in-person)

Treatment Part 2 (MAD)

Multiple ascending dose administration of ADEL-Y01 or placebo to participants with MCI due to AD or mild AD

22 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADEL-Y01

Trial Overview ADEL-Y01 is being tested for safety and how it's processed in the body (pharmacokinetics) in healthy people first (Part 1), then in those with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) later (Part 2). The study compares ADEL-Y01 against a placebo, given once initially then multiple times.

How Is the Trial Designed?

Group I: SAD Cohort 2: ADEL Y-01 antibody at a dose of 7.5mg/Kg Active Control 1 Intervention

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

Group II: MAD Cohort 2: ADEL Y-01 antibody at a dose of 20mg/Kg Active Control 1 Intervention

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

Group III: MAD Cohort 3: ADEL Y-01 antibody at a dose of 50mg/Kg Active Control 1 Intervention

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

Group IV: SAD Cohort 1: ADEL Y-01 antibody at a dose of 2.5mg/Kg Active Control 1 Intervention

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

Group V: SAD Cohort 5: ADEL Y-01 antibody at a dose of 100mg/Kg Active Control 1 Intervention

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

Group VI: SAD Cohort 4: ADEL Y-01 antibody at a dose of 50mg/Kg Active Control 1 Intervention

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

Group VII: SAD Cohort 3: ADEL Y-01 antibody at a dose of 20mg/Kg Active Control 1 Intervention

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

Group VIII: MAD Cohort 1: ADEL Y-01 antibody at a dose of 7.5mg/Kg Active Control 1 Intervention

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

Group IX: SAD Cohort 5: Placebo at a dose of 100mg/Kg Placebo Group 1 Intervention

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

Group X: MAD Cohort 3: Placebo at a dose of 50mg/Kg Placebo Group 1 Intervention

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

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

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

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

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

Group XIII: SAD Cohort 2: Placebo at a dose of 7.5mg/Kg Placebo Group 1 Intervention

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

Group XIV: SAD Cohort 3: Placebo at a dose of 20mg/Kg Placebo Group 1 Intervention

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

Group XV: MAD Cohort 2: Placebo at a dose of 20mg/Kg Placebo Group 1 Intervention

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

Group XVI: SAD Cohort 4: Placebo at a dose of 50mg/Kg Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2

Recruited

7,100+

Oscotec Inc.

Industry Sponsor

Trials

8

Recruited

430+

Published Research Related to This Trial

Younger patients with Alzheimer's disease (YPAD) exhibit distinct clinical features compared to those with late-onset Alzheimer's, highlighting the need for tailored diagnostic and therapeutic approaches.

The Japanese Psychogeriatric Society emphasizes the importance of comprehensive support systems for YPAD, addressing not just treatment but also the broader needs of individuals and their families affected by dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical issues of younger patients with dementia--Japan Psychogeriatric Society]. Arai, H.[2011]

Aducanumab, a monoclonal antibody targeting amyloid β, was approved by the FDA in June 2021 for treating Alzheimer's disease in patients with mild cognitive impairment or mild dementia, based on clinical trials conducted in this specific population.

The long-term safety and tolerability of aducanumab are currently being assessed in a multinational phase 3b clinical study, as there is no data on its effectiveness or safety for patients at different stages of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab: First Approval. Dhillon, S.[2021]

In a study of 98 young-onset Alzheimer's disease (YO-AD) patients and 123 late-onset Alzheimer's disease (LO-AD) patients over 2 years, YO-AD patients generally exhibited lower rates of neuropsychiatric symptoms compared to LO-AD patients, particularly for symptoms like delusions, agitation, and depression.

Apathy was identified as the most prevalent neuropsychiatric symptom in YO-AD patients, highlighting the need for focused attention on this symptom in their diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of neuropsychiatric symptoms in young-onset compared to late-onset Alzheimer's disease - part 1: findings of the two-year longitudinal NeedYD-study. van Vliet, D., de Vugt, ME., Aalten, P., et al.[2013]

The study analyzed neuroimaging data from 36 subjects aged 55-65, including 9 with early-onset Alzheimer's Disease (EO-AD) and 27 with early-onset mild cognitive impairment (EO-MCI), revealing 15 significant neuroimaging markers that differentiate between these two conditions.

Using advanced imaging techniques, the research identified structural brain differences linked to diagnosis, age, education, and genetic factors, which may help in understanding the progression from EO-MCI to EO-AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural Brain Changes in Early-Onset Alzheimer's Disease Subjects Using the LONI Pipeline Environment. Moon, SW., Dinov, ID., Hobel, S., et al.[2018]

Alzheimer's disease drug development faces a significant challenge, with 99% of trials failing to show a difference between drug and placebo, highlighting the need for improved strategies to enhance success rates.

Key strategies for optimizing Alzheimer's drug development include identifying the right biological target, drug, biomarkers, participants, and trial design, which can help increase the likelihood of successful outcomes and attract investment for new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The "rights" of precision drug development for Alzheimer's disease. Cummings, J., Feldman, HH., Scheltens, P.[2023]

YKL-40 levels in cerebrospinal fluid (CSF) are significantly higher in Alzheimer's disease (AD) patients compared to healthy controls, suggesting its potential as a biomarker for early diagnosis and monitoring of AD.

While YKL-40 levels in peripheral blood did not show significant differences overall, plasma levels were notably higher in AD patients, indicating that both CSF and plasma YKL-40 could aid in distinguishing AD patients from healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral Blood and Cerebrospinal Fluid Levels of YKL-40 in Alzheimer's Disease: A Systematic Review and Meta-Analysis. Zhang, Y., Tian, J., Ni, J., et al.[2023]

Aducanumab is a monoclonal antibody that targets aggregated amyloid β (Aβ) in Alzheimer's disease, showing an objective reduction in Aβ levels but conflicting results regarding its clinical efficacy in improving symptoms.

The most significant safety concern associated with aducanumab treatment is the occurrence of amyloid-related imaging abnormalities, which raises questions about its overall risk-benefit profile despite its recent accelerated approval by the FDA for mild Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab for the treatment of Alzheimer's disease. Tagliapietra, M.[2022]

The amyloid hypothesis has guided over 200 clinical trials for Alzheimer's disease treatments, primarily focusing on anti-Aβ immunotherapies, but many have failed to show clear clinical benefits.

Aducanumab, the first anti-Aβ antibody approved by the FDA in 2021, has faced significant criticism regarding its effectiveness and approval process, leading to limited coverage for patients outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from antiamyloid-β immunotherapies in Alzheimer's disease. Plascencia-Villa, G., Perry, G.[2023]

In a study using a 5xFAD mouse model of Alzheimer's disease, increased levels of YKL-40 were found in the cerebrospinal fluid, correlating with activated astrocytes and contributing to synaptic degeneration and cognitive impairment.

Knocking out YKL-40 in astrocytes of symptomatic mice led to reduced amyloid plaque deposition and improved memory function, suggesting that targeting YKL-40 could be a promising strategy to alleviate cognitive deficits in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice. Zeng, X., Cheung, SKK., Shi, M., et al.[2023]

Alzheimer's disease (AD) is linked to elevated levels of amyloid β (Aβ) peptide, particularly soluble Aβ oligomers (AβOs), which are believed to cause memory and cognitive decline; however, traditional therapies targeting Aβ have largely failed in clinical trials.

ACU193 is the first immunotherapeutic specifically designed to target AβOs and is currently undergoing human clinical trials, representing a new approach to potentially halt or reverse cognitive decline in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease. Krafft, GA., Jerecic, J., Siemers, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10104896/

Monoclonal antibody Y01 prevents tauopathy progression ... Monoclonal antibody Y01 prevents tauopathy progression induced by lysine 280–acetylated tau in cell and mouse models.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06247345

NCT06247345 | A Phase Ia/Ib, First-in-human (FIH) Study ... This is a Phase Ia/Ib, two-part, randomized, placebo-controlled, double-blinded, first in human(FIH) study to evaluate the safety, tolerability, PK, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11713122/

Preclinical efficacy and rationale of targeting lysine280‐ ... The Y01 antibody that specifically recognizes acK280 represents a promising therapeutic candidate for AD and other neurodegenerative diseases associated with ...

4. molecularneurodegeneration.biomedcentral.com molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-024-00769-x

Comparing anti-tau antibodies under clinical trials and their ... Our results also suggest that MTBR antibodies are more effective at inhibiting tau seeding and aggregation than N-terminus antibody, aligning ...

5. synapse.patsnap.com synapse.patsnap.com/blog/oscotecadel-begins-phase-1-trial-of-adel-y01-anti-tau-antibody-for-alzheimers

Oscotec/Adel Begins Phase 1 Trial of ADEL-Y01 Anti-Tau ... Published in the prior year, the preclinical findings on ADEL-Y01, explored in animal test subjects, showed a notable reduction in memory ...

6. withpower.com withpower.com/trial/phase-1-alzheimer-disease-2024-15602

ADEL-Y01 for Alzheimer's Disease What safety data exists for ADEL-Y01 (Aducanumab) in humans? Aducanumab, also known as Aduhelm, has been studied for Alzheimer's disease and received FDA ...

7. practicalneurology.com practicalneurology.com/news/novel-monoclonal-antibody-which-targets-tau-protein-accumulation-receives-ind-clearance-from-fda/2470293/

Novel Monoclonal Antibody Which Targets Tau Protein ... The safety, tolerability, and pharmacokinetics of ADEL-Y01 will be assessed in a phase 1a/1b study which will include both healthy ...

8. synapse.patsnap.com synapse.patsnap.com/drug/a8884bd010cf45778fc06524934f84ec

ADEL-Y01 - Drug Targets, Indications, Patents This phase 1a/1b study in the U.S. is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of ADEL-Y01 in 40 healthy volunteers as well ...