early Alzheimer’s disease MedDRA version: 20.0 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
ADvantage Therapeutics GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 50-85 years old 2. 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 3. Has a Mini-Mental State Examination (MMSE) score between 22 and 30 Note: Regarding inclusion criterion #2, it is obvious that patients with an MMSE score =27 may not fulfill all NINCDS/ADRDA criteria, especially those referring to or requiring a state of dementia. In such cases, inclusion criteria #4 and #5 ensure the specificity of the diagnosis (prodromal stage of AD/AD-type mild cognitive impairment [MCI]). 4. 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. 5. 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 6. Must have results of a physical examination, including visual and auditory acuity within the acceptable range for the age group to allow neuropsychological testing 7. Has Hachinski Ischemia Scale score =4 to distinguish AD from vascular dementia 8. Written informed consent of study-related procedures and of genetic investigations signed and dated by the patient and the caregiver. 9. 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 10. Women of childbearing potential and men with female partners of childbearing potential must use an 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* 11. Women of childbearing potential and men with female partners of childbearing potential must use 2 effective method 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 (see additional considerations in Section 5.3)** * = This inclusion criterion is only valid for patients enrolled in Germany. ** = This inclusion criterion is only valid for patients enrolled in Austria, Bulgaria, France, Slovakia and Poland. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 61 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 61
Exclusion criteria
Exclusion criteria: 1. Known or suspected allergy, or history of anaphylaxis, to vaccines or their excipients, if considered relevant by the Investigator 2. Any medical or neurological condition (other than AD) that might cause the participant’s cognitive impairment including e.g. - 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 - 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 (C-SSRS), 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 - History within the last 2 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen posttreatment; or has a life expectancy of <2 years. 3. Presence of end stage kidney failure (on dialysis) (which may affect renal clearance of aluminium) 4. Patient has hemochromatosis 5. If on conventional AD therapies such as donepezil or memantine, anticholinergics in general (including neuroleptics with anticholinergic properties, certain bladder relaxants, anticholinergic drugs for use in lung diseases), or lipid-modifying therapies, doses must be stable for at least 3 months prior to the screening visit and during the entire trial period 6. Current or anticipated use of immunosuppressive drugs such as, but not limited to, azathioprine, cyclosporine, methotrexate, tacrolimus, or mycophenylate within 2 months or any myelosuppressive or cytotoxic chemotherapies within the 12 months prior to the screening visit. Use of systemic corticosteroids equivalent to =20mg/week prednisone within the past 4 weeks before screening and during the course of the study (intranasal or inhaled steroids for allergies/asthma is allowed) 7. Current or anticipated use of allergy immunotherapies 8. Patient has received or plans to receive any aluminium-adjuvanted vaccines within 14 days prior to any dose of study drug 9. Pregnancy (for patients of childbearing potential, see additional considerations in Section 5.3) 10. Contraindication for MRI imaging, including but not limited to pacemakers; cochlear implants, cerebral aneurysm clips; implanted infusion pumps; implanted nerv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of AD04 in slowing progression of the disease in patients with early Alzheimer’s disease (AD) based on the evaluation of the time savings in cognitive, functional and global domains over 6 months ;Secondary Objective: - To investigate safety and tolerability of AD04 in early AD patients over 12 months - To assess the effect of AD04 in global clinical activity and quality of life over 12 months - To obtain surrogate biomarkers of AD (wet and structural), immunity, and lipid metabolism over 12 months ;Primary end point(s): Composite score assessing cognition [adapted AD Assessment Scale cognitive (aADAS-cog)], daily function [adapted AD Cooperative Study Activities of Daily Living (aADCS-ADL)] and CDR-sb over 6 months measured in overall time saved with treatment;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Endpoints - Incidence of treatment-emergent adverse events (TEAEs) Key Secondary Efficacy Endpoint - Change from baseline in Clinical Dementia Rating - sum of boxes (CDR-sb) Other Secondary Efficacy Endpoints - Global statistical test (GST) combining cognition [ADAS-cog] and daily function [ADCS-ADL] - Change from baseline in hippocampal volume (total, right, and left), measured by volumetric Magnetic Resonance Imaging (MRI) -Change from baseline in cognition score (ADAS-cog and aADAS-cog) - Change from baseline in function score (ADCS-ADL and aADCS-ADL) - Neuropsychiatric inventory (NPI) -Clinician’s Global Impressions of Change (CGIC) Assessment of Quality of Life in patients with AD and their caregivers (QOL-AD) Exploratory endpoints The following biomarkers will be measured to support treatment effect and dosing regimen: -Concentrations of aluminium in the blood, cerebrospinal fluid (CSF), and urine for pharmacokinetic profiling of AD04 (AUC and cumulative maximum concentration adjusted for pre-dose baseline values) -Levels of circulating biomarkers of immune response, lipid metabolism, neuroinflammation, and brain atrophy (temporal dynamics and time dependencies) - PK/PD relationships (e.g., based on aluminium and IgG antibody measurements) ;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
Austria, Bulgaria, France, Germany, Poland, Slovakia
Contacts
Public ContactClinical Trials Information
ADvantage Therapeutics GmbH
Outcome results
None listed