24 Months Safety and Efficacy Study of AADvac1 in Patients With Mild Alzheimer's Disease

• Status: Completed
• Trial end date: 2019-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the safety and efficacy of AADvac1 in the treatment of patients with mild Alzheimer's disease.

60% of participants will receive AADvac1 and 40% of participants will receive placebo.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Axon Neuroscience SE
• Treatments: Aluminum Hydroxide

Criteria

Inclusion criteria (abbreviated):

• Diagnosis of probable Alzheimer's disease according to the revised National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (McKhann 2011).

• Mini Mental State Examination (MMSE) score ≥ 20 and ≤ 26.

• Brain MRI finding consistent with the diagnosis of Alzheimer's disease

• Medial temporal lobe atrophy: Scheltens score of ≥ 2 (on a scale of 0-4 on the more atrophied side) AND/OR positive AD biomarker profile in the CSF (amyloid+, tau+)

• At least 6 years of formal elementary education.

• Age 50-85 years.

• Fluency in the local language and sufficient auditory and visual capacities to allow neuropsychological testing.

• Ability to read and understand the informed consent.

• Stable therapy with an acetylcholinesterase inhibitor for at least 3 months prior to screening.

• If the patient is on memantine treatment, the dose regimen must be stable for at least 3 months prior to screening.

• Hachinski Ischemia Scale score ≤ 4.

• Availability of a caregiver.

• Female patients must be either surgically sterile or at least 2 years postmenopausal.

• Male patients must either be surgically sterile, or he and his female spouse/partner who is of childbearing potential must be using highly effective contraception starting at screening and continuing throughout the study period.

• Patient provides written informed consent.

Exclusion criteria (abbreviated):

• Participation in another clinical study within 3 months prior to screening.

• Pregnant or breastfeeding female.

• Not expected to complete the clinical study.

• Known allergy to components of the vaccine.

• Contraindication for MRI imaging.

• Any of the following detected by brain MRI:

• Infarction in the territory of large vessels

• More than one lacunar infarct.

• Any lacunar infarct in a strategically important location.

• Confluent hemispheric deep white matter lesions (Fazekas grade 3).

• Other focal lesions which may be responsible for the cognitive status of the patient or any other abnormalities associated with significant central nervous disease other than Alzheimer's disease.

• Surgery (under general anaesthesia) within 3 months prior to screening and/or scheduled surgery (under general anaesthesia) during the whole study period.

• Patient has a history and/or currently suffers from a clinically significant autoimmune disease, or is expected to receive immunosuppressive or immunomodulatory treatment at the present or in the future.

• Recent history of cancer (last specific treatment ≤ 5 years prior to Screening).

• Myocardial infarction within 2 years prior to screening.

• Hepatitis B, C, HIV or Syphilis.

• Active infectious disease.

• Presence and/or history of immunodeficiency.

• Patient currently suffering from a clinically important systemic illness:

• poorly controlled congestive heart failure (NYHA ≥ 3)

• BMI > 40

• poorly controlled diabetes (HbA1c > 7.5%)

• severe renal insufficiency (eGFR < 30 mL/min)

• chronic liver disease - ALT (alanine aminotransferase) > 66 U/L in females or > 80 U/L in males, AST (aspartate aminotransferase) > 82 U/L

• QTc interval prolongation in ECG (> 450 ms)

• other clinically significant systemic illness, if considered relevant by the investigator

• Hypothyroidism, defined as TSH (thyroid-stimulating hormone) elevation > 5.000 mcIU/mL, and/or FT4 levels < 0.7 ng/dL. Patients with corrected hypothyroidism are eligible for the study provided that treatment has been stable for 3 months before study entry.

• Valid diagnosis of a significant psychiatric illness such as schizophrenia, any type of psychotic disorder or bipolar affective disorder.

• Current depressive episode (Geriatric Depression Scale GDS ≥ 6) or major depressive episode within the last 1 years.

• Metabolic or toxic encephalopathy or dementia due to a general medical condition.

• History of alcohol or drug abuse or dependence within the past 2 years.

• Wernicke's encephalopathy.

• History or evidence of any CNS disorder other than AD that could be the cause of dementia.

• Cerebrovascular disease (ischemic or haemorrhagic stroke), or diagnosis of possible, probable or definite vascular dementia.

• Epilepsy.

• Treatment with experimental immunotherapeutics including intravenous immunoglobulin within 3 months prior to screening.

• Treatment with experimental therapies for AD aiming at disease-modification within 3 months prior to screening.

• Patient is currently being treated or was treated in the past with any active vaccines for AD.

• Treatment with immunosuppressive drugs.

• Change in dose of previous and current medications within the last 30 days prior to Screening (V01), if considered clinically relevant by the investigator.

• Vitamin B12 deficiency (serum vitamin B12 < 191 pg/mL).