Effects of a Widely Used Vaccine Adjuvant in Subjects With Early Alzheimer's Disease Double-blind Study to Assess the Safety and Efficacy of AD04 in Patients With Early Alzheimer's Disease - ADVANCE

NCT07107074 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ADVANCE-AD04-001
• Study Type: interventional
• Target: 122
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of this randomized, placebo-controlled phase 2b study is to prospectively evaluate AD04's potential as a disease-modifying drug in AD. By evaluating the safety, pharmacodynamics, and efficacy of AD04 in early AD patients, we aim to deliver a comprehensive and robust data set that furthers our understanding of the effects of AD04 in AD pathology.

Conditions

Alzheimer Disease, Early Onset

Outcome Measures

Primary Outcomes (1)

• Composite score assessing cognition (aADAS-cog), daily function Activities of Daily Living (aADCS-ADL) and a global dementia severity score (CDR-sb) over 6 months measured in overall time saved with treatment

  Based on the evaluation of the time savings in cognitive, functional and global domains.

  6 months

Secondary Outcomes (3)

• Incidence of treatment-emergent adverse events (TEAEs)

  12 months

• Change from baseline in Clinical Dementia Rating - sum of boxes (CDRsb)

  12 months

• Change from baseline in hippocampal volume (total, right, and left), measured by volumetric Magnetic Resonance Imaging (MRI)

  12 Months

Study Arms (2)

1ml AD04

EXPERIMENTAL

Each patient will receive 6 single s.c. injections of IMP at monthly intervals over a 5-month treatment period.

Drug: AD04

1ml PBS

PLACEBO COMPARATOR

Each patient will receive 6 single s.c. injections of placebo at monthly intervals over a 5-month treatment period.

Drug: Placebo

Interventions

AD04 DRUG

Each patient will receive 6 single s.c. injections of IMP at monthly intervals over a 5-month treatment period.

1ml AD04

Placebo DRUG

Each patient will receive 6 single s.c. injections of Placebo at monthly intervals over a 5-month treatment period.

1ml PBS

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 50-85 years old
• Has a diagnosis of probable AD based on the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, integrating both clinical and neuropathological criteria
• Has brain MRI showing medial temporal lobe atrophy as assessed by the Scheltens' scale (score ≥2, at least at one site) or has AD-type CSF signature at a 7:3 ratio of Scheltens to CSF signature. This criterion was chosen with the goal of having a patient cohort which reflects as closely as possible that of the AFF006 study; specific cut-offs for CSF AD biomarkers will be defined based on the methodology of the selected central laboratory.
• Has a Free and Cued Selective Reminding Test (FCSRT) total recall ≤40 or free recall ≤17, indicating hippocampal damage, episodic memory impairment, and amnestic syndrome
• Must have results of a physical examination, including visual and auditory acuity within the acceptable range for the age group to allow neuropsychological testing
• Has Hachinski Ischemia Scale score ≤4 to distinguish AD from vascular dementia
• Written informed consent of study-related procedures and of genetic investigations signed and dated by the patient and the caregiver
• Availability of a partner/caregiver knowing the patient and being able to accompany the patient at the visits. He/ she will be in frequent contact with the participant (defined as at least 10 hours per week), will accompany the participant to the planned study visits and/or be available by telephone at designated times
• Women of childbearing potential and men with female partners of childbearing potential must use 2 effective methods of birth control during the course of the trial and for at least 90 days after the last dose in a manner such that risk of failure is minimized. Male participants should refrain from donating sperm during the intervention period and for at least 90 days after the last dose of study intervention

You may not qualify if:

• Known or suspected allergy, or history of anaphylaxis, to vaccines or their excipients, if considered relevant by the Investigator
• Any medical or neurological condition (other than AD) that might cause the participant's cognitive impairment, including:
• History or evidence of cerebrovascular disease (stroke, transient ischemic attack, intracerebral hemorrhage), or diagnosis of possible, probable or definite vascular dementia in accordance with National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria
• A significant number of \>4 microhemorrhages, a single prior hemorrhage \> 1 cm3, \>2 lacunar infarcts, a single prior infarct \> 1 cm3, radiological finding supporting the NINDS-AIREN criteria as operationalized in Stroke. 2003 Aug;34(8):1907-12, meningioma with a perpendicular diameter of \>1cm or significant mass effect on the brain parenchyma, evidence of a cerebral contusion, encephalomalacia, aneurysms, brain neoplasms such as gliomas or subdural hematoma/effusion with a diameter of \>1cm, diffuse white matter disease (Fazekas score - deep white matter score \>3) or significant mass effect on the brain parenchyma assessed by MRI at screening
• Evidence of a clinically relevant Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, mental retardation, hypoxic cerebral damage, or head trauma with loss of consciousness that led to persistent cognitive deficits
• Refractory epilepsy (has had seizures within the past 2 years)
• Has had a history within the last 5 years of a serious infectious disease affecting the brain
• Clinically significant unstable psychiatric illness in the past 6 months
• Has a Geriatric Depression Scale score \> 6 (on the staffadministered short form)
• Hypothyroidism or vitamin B12 deficiency (patients with corrected hypothyroidism or vitamin B12 deficiency are eligible for the study provided that treatment has been stable for 3 months before study entry)
• Patients with long covid-19 showing long-term neurological sequelae within the past 12 months at the time of screening
• History of chronic alcohol or drug abuse/ dependence within the past 5 years
• Patient with past or present suicidal ideation and intent as assessed by the Columbia Suicidality Severity Rating Scale (CSSRS), or who, in the clinical judgment of the investigator, presents a serious risk of suicide
• Presence of autoimmune disease, autoinflammatory syndrome, or immunological deficiency syndrome (including human immunodeficiency virus (HIV) infection)
• Relevant cardiovascular, hepatic, gastroenterological, respiratory, endocrinological, hematologic disease, or any other condition that, in the Investigator's opinion, could interfere with the analyses of safety and efficacy in this study, unless patient has been on stable doses of medication for any of these concurrent illnesses for at least 3 months prior to study entry

Sponsors & Collaborators

• ADvantage Therapeutics: lead

Study Sites (3)

Institute Neuromed

Korneuburg, Lower Austria, 2100, Austria

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

Promente-Centrum Neurologii i Psychogeriatrii

Bydgoszcz, 85-133, Poland

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Achim Schneeberger, MD

  ADvantage Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: August 6, 2025
• Study Start: November 8, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2); AU (1)