ADEL-Y01 for Alzheimer's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
Trial Summary
What is the purpose of this trial?
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 \[MAD\]).
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.
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 approval in 2021. The most significant safety concern noted in trials is amyloid-related imaging abnormalities, which are changes seen in brain scans. Long-term safety is still being evaluated in ongoing studies.12345
How does the drug ADEL-Y01 differ from other Alzheimer's treatments?
Eligibility Criteria
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 between 18 and 65 years old and cannot become pregnant.
I am a male willing to use condoms and spermicide for 3 months after treatment.
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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
See 16 more
Trial Timeline
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
Treatment Details
Interventions
- ADEL-Y01 (Virus Therapy)
Trial OverviewADEL-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.
Participant Groups
16Treatment groups
Active Control
Placebo Group
Group I: SAD Cohort 2: ADEL Y-01 antibody at a dose of 7.5mg/KgActive Control1 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/KgActive Control1 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/KgActive Control1 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/KgActive Control1 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/KgActive Control1 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/KgActive Control1 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/KgActive Control1 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/KgActive Control1 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/KgPlacebo Group1 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/KgPlacebo Group1 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/KgPlacebo Group1 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/KgPlacebo Group1 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/KgPlacebo Group1 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/KgPlacebo Group1 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/KgPlacebo Group1 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/KgPlacebo Group1 Intervention
This arm represents the group receiving placebo at a dose of 50mg/Kg in SAD cohort 4.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
CenExel ACTAnaheim, CA
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Who Is Running the Clinical Trial?
Alzheimer's Disease Expert Lab (ADEL), Inc.Lead Sponsor
Oscotec Inc.Industry Sponsor
References
Aducanumab: First Approval. [2021]Aducanumab (aducanumab-avwa; Aduhelm™) is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid β. It has been co-developed by Biogen and Eisai under license from Neurimmune for the treatment of Alzheimer's disease. In June 2021, aducanumab received its first approval in the USA for the treatment of Alzheimer's disease. According to the US FDA prescribing information, treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. Aducanumab is under regulatory review in Japan and in Europe. Its long-term safety and tolerability is being evaluated in a multinational phase 3b clinical study in patients with early Alzheimer's disease (mild cognitive impairment and mild Alzheimer's disease). This article summarizes the milestones in the development of aducanumab leading to this first approval for Alzheimer's disease.
ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer's Disease. [2022]Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects 50 million people worldwide, with 10 million new cases occurring each year. The emotional and economic impacts of AD on patients and families are devastating. Approved treatments confer modest improvement in symptoms, and recently one treatment obtained accelerated approval from the United States Food and Drug Administration (FDA) and may have modest disease modifying benefit. Research over the past three decades has established a clear causal linkage between AD and elevated brain levels of amyloid β (Aβ) peptide, and substantial evidence now implicates soluble, non-fibrillar Aβ oligomers (AβOs) as the molecular assemblies directly responsible for AD-associated memory and cognitive failure and accompanying progressive neurodegeneration. The widely recognized linkage of elevated Aβ and AD spawned a comprehensive 20-year therapeutic campaign that focused primarily on two strategies - inhibition of the secretase enzymes responsible for Aβ production and clearance of Aβ peptide or amyloid plaques with Aβ-directed immunotherapeutics. Unfortunately, all clinical trials of secretase inhibitors were unsuccessful. Of the completed phase 3 immunotherapy programs, bapineuzumab (targeting amyloid plaque) and solanezumab (targeting Aβ monomers) were negative, and the crenezumab program (targeting Aβ monomers and to a small extent oligomers) was stopped for futility. Aducanumab (targeting amyloid plaques), which recently received FDA accelerated approval, had one positive and one negative phase 3 trial. More than 25 negative randomized clinical trials (RCTs) have evaluated Aβ-targeting therapeutics, yet none has directly evaluated whether selective blockage of disease-relevant AβOs can stop or reverse AD-associated cognitive decline. Here, we briefly summarize studies that establish the AD therapeutic rationale to target AβOs selectively, and we describe ACU193, the first AβO-selective immunotherapeutic to enter human clinical trials and the first positioned to test the AβO hypothesis of AD.
The "rights" of precision drug development for Alzheimer's disease. [2023]There is a high rate of failure in Alzheimer's disease (AD) drug development with 99% of trials showing no drug-placebo difference. This low rate of success delays new treatments for patients and discourages investment in AD drug development. Studies across drug development programs in multiple disorders have identified important strategies for decreasing the risk and increasing the likelihood of success in drug development programs. These experiences provide guidance for the optimization of AD drug development. The "rights" of AD drug development include the right target, right drug, right biomarker, right participant, and right trial. The right target identifies the appropriate biologic process for an AD therapeutic intervention. The right drug must have well-understood pharmacokinetic and pharmacodynamic features, ability to penetrate the blood-brain barrier, efficacy demonstrated in animals, maximum tolerated dose established in phase I, and acceptable toxicity. The right biomarkers include participant selection biomarkers, target engagement biomarkers, biomarkers supportive of disease modification, and biomarkers for side effect monitoring. The right participant hinges on the identification of the phase of AD (preclinical, prodromal, dementia). Severity of disease and drug mechanism both have a role in defining the right participant. The right trial is a well-conducted trial with appropriate clinical and biomarker outcomes collected over an appropriate period of time, powered to detect a clinically meaningful drug-placebo difference, and anticipating variability introduced by globalization. We lack understanding of some critical aspects of disease biology and drug action that may affect the success of development programs even when the "rights" are adhered to. Attention to disciplined drug development will increase the likelihood of success, decrease the risks associated with AD drug development, enhance the ability to attract investment, and make it more likely that new therapies will become available to those with or vulnerable to the emergence of AD.
Aducanumab for the treatment of Alzheimer's disease. [2022]Alzheimer's disease (AD) is the most frequent neurodegenerative condition, the most common cause of dementia, and a leading cause of disability and death globally. Mounting evidence supported accumulation of amyloid β (Aβ) as the primary cause of AD pathology and sprouted a number of candidate treatments engaging Aβ from its production to its clearance, yet no amyloid-based drug candidate had been proven effective. Alternative pathomechanisms have been proposed, but still current treatments are limited to symptomatic therapy. Aducanumab (BIIB-037) is a fully human monoclonal IgG1 antibody that selectively binds aggregated forms of Aβ, inhibits its template activity and promotes clearance of Aβ deposits. Three early terminated trials in humans are available. Overall, conflicting results exist over measures of clinical efficacy, despite an objective decrease in Aβ burden. Amyloid-related imaging abnormalities emerge as the most significant treatment-related adverse event. Here, we provide a comprehensive review of the available evidence on aducanumab, a drug that recently received a debated accelerated approval for the treatment of mild AD by the U.S. Food and Drug Administration (FDA).
Lessons from antiamyloid-β immunotherapies in Alzheimer's disease. [2023]The amyloid hypothesis, that established amyloid-β (Aβ) peptide as the primary cause of Alzheimer's disease (AD) and related dementia, has driven the development of treatments for neurodegeneration for 30 years. During the last decades, more than 200 clinical trials testing more than 30 anti-Aβ immunotherapies have been assessed as potential treatments for AD. A vaccine against Aβ was the first immunotherapy intended to avoid aggregation of Aβ into fibrils and senile plaques, but it dramatically failed. Several other vaccines have been proposed as potential AD treatments, targeting different domains or structural motifs of Aβ aggregates, but without clear clinical benefits or effectiveness. In contrast, anti-Aβ therapeutic antibodies have focused on recognizing and removing Aβ aggregates (oligomers, fibrils, or plaques) by eliciting immune clearance. In 2021, the first anti-Aβ antibody, aducanumab (branded as Aduhelm), received FDA approval under an accelerated approval process. The effectiveness and the overall processes regarding the approval of Aduhelm have been under major criticism and scrutiny, prompting a vote of no confidence by public and private health providers, limiting the coverage only to patients enrolled in clinical trials and not for the general elderly patients. Additionally, another three therapeutic anti-Aβ antibodies are following the same path for potential FDA approval. Here, we present the current status of anti-Aβ immunotherapies under evaluation in preclinical and clinical trials for the treatment of AD and related dementia, with a discussion of the main findings and critical lessons learned from the observations from Phase III, II, and I clinical trials of anti-Aβ vaccines and antibodies.
Prevalence of neuropsychiatric symptoms in young-onset compared to late-onset Alzheimer's disease - part 1: findings of the two-year longitudinal NeedYD-study. [2013]Knowledge about neuropsychiatric symptoms in young-onset Alzheimer's disease (YO-AD) is scarce, but essential to establish a prognosis and plan care for YO-AD patients. The aim of this study is to assess frequency parameters of neuropsychiatric symptoms in YO-AD over 2 years and investigate whether there are differences compared with late-onset Alzheimer's disease (LO-AD).
Peripheral Blood and Cerebrospinal Fluid Levels of YKL-40 in Alzheimer's Disease: A Systematic Review and Meta-Analysis. [2023]The pathogenesis associated with Alzheimer's disease (AD) is particularly complicated, and early diagnosis and course monitoring of the disease are not ideal based on the available core biomarkers. As a biomarker closely related to neuroinflammation, YKL-40 provides a potential scalable approach in AD, but its association remains controversial and inconclusive with AD. We conducted this study to assess the utility of YKL-40 levels in peripheral blood and cerebrospinal fluid (CSF) of AD patients and healthy controls (HCs) by meta-analysis. We systematically searched and screened relevant trials for comparing YKL-40 levels between AD patients and HCs in PubMed, Embase, Cochrane, and Web of Science, with a search deadline of 14 March 2023 for each database. A total of 17 eligible and relevant studies involving 1811 subjects, including 949 AD patients and 862 HCs, were included. The results showed that YKL-40 levels in the peripheral blood of AD patients and HCs did not possess significant differences. Subgroup analysis showed YKL-40 significantly differed in plasma (SMD = 0.527, 95%CI: [0.302, 0.752]; p = 0.000), but did not in serum. In the case of comparison with HCs, YKL-40 was significantly higher in CSF of AD patients (SMD = 0.893, 95%CI: [0.665, 1.121]; p = 0.000). Besides that, when we performed a combined analysis of total YKL-40 in both peripheral blood and CSF, overall YKL-40 concentrations were also significantly increased among AD patients (SMD = 0.608, 95%CI: [0.272, 0.943]; p = 0.000). YKL-40 provides support and rationale for the neuroinflammatory pathogenesis of AD. The significance of CSF levels of YKL-40 for early screening of AD is definite. Plasma levels of YKL-40 also appear to assist in discriminating AD patients from HCs, which facilitates early screening and monitoring of the natural course of AD.
Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice. [2023]Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer's disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer's disease. High levels of YKL-40 are associated with either advanced Alzheimer's disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer's disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer's disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aβ1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aβ1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aβ1-42 peptides, increased rate of Aβ1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer's disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer's disease patients.
[Clinical issues of younger patients with dementia--Japan Psychogeriatric Society]. [2011]Younger patients with Alzheimer's disease (YPAD) present many clinical aspects different from people with late-onset Alzheimer's disease. The author reviewed terminological, diagnostic, and therapeutic issues, as well as support systems for YPAD and concerns related to disclosure. The Japanese Psychogeriatric Society is a leader in this field, focusing not only on treatment of AD, but also comprehensive support systems for people with dementia.
Structural Brain Changes in Early-Onset Alzheimer's Disease Subjects Using the LONI Pipeline Environment. [2018]This study investigates 36 subjects aged 55-65 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to expand our knowledge of early-onset (EO) Alzheimer's Disease (EO-AD) using neuroimaging biomarkers.