An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects (APOLLOE4)

• ClinicalTrials.gov Identifier: NCT04770220
• Recruitment Status: Active, not recruiting
• First Posted: February 25, 2021
• Last Update Posted: May 16, 2024
• Sponsor: Alzheon Inc.
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Alzheon Inc.

Tracking Information

• First Submitted Date: February 22, 2021
• First Posted Date: February 25, 2021
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: May 19, 2021
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2021)

• Primary cognitive efficacy endpoint [ Time Frame: Week 78 ]
  Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks
• Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE) [ Time Frame: Week 78 ]
  Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAE, and TEAE leading to withdrawal.
• Primary fluid biomarker endpoint 1 [ Time Frame: Week 78 ]
  Change from baseline in cerebrospinal fluid p-tau181 levels in sub-study
• Primary fluid biomarker endpoint 2 [ Time Frame: Week 78 ]
  Change from baseline in plasma p-tau181 levels
• Primary imaging biomarker endpoint [ Time Frame: Week 78 ]
  Change from baseline in total hippocampal volume (mm3) as measured by Magnetic Resonance Imaging (MRI)

Original Primary Outcome Measures (submitted: February 22, 2021)

• Primary cognitive efficacy endpoint [ Time Frame: Week 78 ]
  Change from baseline in ADAS-cog 13 scores
• Primary safety and tolerability endpoint [ Time Frame: Week 78 ]
  Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAE, and TEAE leading to withdrawal.
• Primary fluid biomarker endpoint 1 [ Time Frame: Week 78 ]
  Change from baseline in cerebrospinal fluid p-tau181 levels in sub-study
• Primary fluid biomarker endpoint 2 [ Time Frame: Week 78 ]
  Change from baseline in plasma p-tau181 levels
• Primary imaging biomarker endpoint [ Time Frame: Week 78 ]
  Change from baseline in total hippocampal volume (mm3) as measured by Magnetic Resonance Imaging (MRI)

Current Secondary Outcome Measures (submitted: February 25, 2021)

• Functional assessment 1 [ Time Frame: Week 78 ]
  Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores
• Global assessment [ Time Frame: Week 78 ]
  Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores
• Functional assessment 2 [ Time Frame: Week 78 ]
  Change from baseline in Disability Assessment for Dementia (DAD)scores

Original Secondary Outcome Measures (submitted: February 22, 2021)

• Functional assessment 1 [ Time Frame: Week 78 ]
  Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores
• Global assessment [ Time Frame: Week 78 ]
  Change from baseline in CDR-SB scores
• Functional assessment 2 [ Time Frame: Week 78 ]
  Change from baseline in Disability Assessment for Dementia scores

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety and Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease and APOE4/4 Genotype
• Brief Summary: This study is being conducted to evaluate the safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is a double-blind, randomized trial with one dose of ALZ-801 compared to placebo.
• Detailed Description: This is a multi-center, double-blind study that will evaluate 265 mg BID of ALZ-801, an oral tablet, over 78 weeks as a treatment for subjects (50-80 years old) with Early AD who are homozygous for the ε4 allele of the apolipoprotein gene (APOE4 homozygous or APOE4/4). The primary efficacy outcome assessment is a measure of cognition (ADAS-cog 13). Additional measures of global and functional impairments will also be assessed. Imaging and soluble biomarkers of AD and neurodegeneration will be measured and a sub-study to evaluate cerebrospinal fluid (CSF) biomarkers is also included.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a multi-center Phase 3, randomized, double-blind, placebo-controlled, parallel-group study.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

• Condition: Early Alzheimer's Disease

Intervention

• Drug: Experimental: ALZ-801
  ALZ-801 tablet 265 mg BID
• Drug: Placebo Comparator: Placebo
  Placebo tablet BID

Study Arms

• Experimental: ALZ-801
  ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID.
  Intervention: Drug: Experimental: ALZ-801
• Placebo Comparator: Placebo
  Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study
  Intervention: Drug: Placebo Comparator: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 22, 2021): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: May 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Clinical diagnosis of MCI or Mild Dementia due to AD consistent with the National Institute on Aging-Alzheimer's Association (NIA-AA) Working Group Criteria.
• Homozygous for the ε4 allele of the apolipoprotein E gene (APOE4/4).
• MMSE score at Screening of 22 to 30 (inclusive).
• CDR - Global score of 0.5 or 1 and CDR Memory Box Score of ≥ 0.5.
• RBANS delayed memory index score ≤ 85.
• Evidence of progressive memory loss over the last 12 months per investigator assessment

Exclusion Criteria:

• Brain magnetic resonance imaging (MRI) indicative of significant abnormality per central reader, other than AD related atrophy. Computed tomography (CT) scan acceptable for subjects who cannot undergo MRI.
• Diagnosis of neurodegenerative disorder other than AD.
• Diagnosis of major depressive disorder (MDD) within one year prior to screening.
• Currently taking memantine or has taken memantine within 12 weeks prior to the Baseline Visit.
• History of suicidal behavior within one year prior to screening or has ongoing suicidal ideation.
• History of seizures, excluding febrile seizures of childhood or a single distant seizure (> 5 years).
• Medically confirmed history of recent cerebral infarct or transient ischemic attack within one year prior to screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, France, Germany, Iceland, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04770220
• Other Study ID Numbers: ALZ-801-AD301; R01AG065253 ( U.S. NIH Grant/Contract ); 2020-005755-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alzheon Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alzheon Inc.
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Aging (NIA)

Investigators

• Principal Investigator: Susan Abushakra, MD; Alzheon Inc.

• PRS Account: Alzheon Inc.
• Verification Date: May 2024