Alzheimer's Disease form of Dementia
Conditions
Interventions
Group 1 (with ACI-35.030 or placebo) will have three sub-groups with different
doses of the vaccine:
• Sub-group 1.1: The participants of this sub-group have already been enrolled
and received 300 µ
Sponsors
AC Immune SA
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria 1. Male or female with age from 50 and up to 75 years old inclusive. 2. Mild Cognitive Impairment (MCI) due to AD or Mild AD according to NIA-AA criteria and a Clinical Dementia Rating scale (CDR) global score of 0.5 or 1 respectively. 3. Mini Mental State Examination (MMSE) score of 22 or above. 4. Abnormal level of CSF Abeta amyloid 42 (Aß42) consistent with AD pathology at screening. • In borderline cases for CSF Aß42 levels, other results may be considered to help determine amyloid positivity e.g. the Aß42/Aß40 ratio and, on a case by case basis, a history of positive amyloid PET scan or positive CSF Aß42 level. • Results from CSF sampling performed within 6 months prior to screening are acceptable on a case by case basis provided that they are consistent with the presence of amyloid pathology and that the corresponding CSF sample can be used in the study for testing. 5. Subjects either not taking any marketed treatment for AD or receiving a stable dose of an acetylcholinesterase inhibitor and/or memantine for at least 3 months prior to baseline. 6. Subjects cared for by a reliable informant or caregiver to assure compliance, assist with clinical assessments and report safety issues. 7. Women must be post-menopausal for at least one year and/or surgically sterilized. Women of childbearing potential or not post-menopausal must have a negative blood pregnancy test at screening (blood draw between day -14 and day -3 prior to baseline) and be willing to use highly effective methods of contraception from the screening visit until the end of their participation. Urine pregnancy testing will be performed throughout the treatment period to determine if the subject can continue receiving the study vaccine. Male participants in the trial with female partners of child bearing potential are required to use barrier methods of contraception (condoms with spermicide) in addition to contraceptive measures used by female partners during the whole study duration. 8. Subjects who in the opinion of the investigator are able to understand and provide written informed consent. In the Netherlands, the subjects* decisional capacity will be also assessed and must be consistent with the ability to provide informed consent using the MacArthur Competency Tool for Clinical Research in order to evaluate their abilities in the areas of understanding, reasoning, appreciation and choice. 9. Both subject and informant or caregiver must be fluent in one of the languages of the study and able to comply with all study procedures, including lumbar punctures.
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Participation in previous clinical trials for AD and/or for neurological disorders using active immunization unless there is documented evidence that the subject was treated with placebo only and the placebo vaccine is not expected to induce any specific immune response. 2. Participation in previous clinical trials for AD and/or for neurological disorders using any passive immunization within the past 6 months (or 5 half-lives of the investigational antibody, whichever is longer) prior to screening unless there is documented evidence that the subject was treated with placebo only and the placebo is not expected to induce any specific immune response. 3. Participation in previous clinical trials for AD and/or for neurological disorders using any small molecule drug including BACE-1 inhibitors within the past 3 months prior to screening. 4. Concomitant participation in any other clinical trial using experimental or approved medications or therapies. 5. Presence of positive Anti-nuclear Antibody (ANA) titers at a dilution of at least 1:160 in subjects without clinical symptoms of auto-immune disease. 6. Current or past history of auto-immune disease, or clinical symptoms consistent with the presence of auto-immune disease. 7. Immune suppression including but not limited to the use of immunosuppressive drugs or systemic steroids unless they have been prescribed transiently more than 3 months prior to screening. 8. History of severe allergic reaction (e.g., anaphylaxis) including but not limited to severe allergic reaction to previous vaccines and/or medications. 9. Prior history of clinically significant hypoglycaemic episodes. 10. Clinically significant deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints Safety and tolerability: Adverse events, immediate and delayed reactogenicity (e.g. anaphylaxis, local and systemic reactogenicity, including immune-complex disease); suicidal ideation (C-SSRS); behavior (NPI); cognitive and functional assessments (RBANS, CDR-SB) to assess safety; vital signs; MRI imaging; electrocardiogram; routine hematology and biochemistry evaluation in blood and urine; evaluation of autoimmune antibodies including anti-dsDNA antibodies in blood; inflammatory markers in blood and CSF Immune response (i.e. immunogenicity): Anti-pTau IgG titers in serum (geometric mean, change from baseline, responder rate, peak and area under the curve) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints Immune response (i.e. immunogenicity): Anti-Tau IgG, anti-pTau and anti-Tau IgM titers in serum (geometric mean, change from baseline, responder rate, peak and area under the curve), determination of the IgG response profile by avidity testing Exploratory Endpoints Change from baseline of putative AD biomarker titers in blood and/or CSF (e.g. total Tau, pTau), change from baseline in T-cell activation levels as measured in blood, change from baseline of inflammatory cytokine titers in blood, change from baseline in antibody titers in blood, change from baseline in behavior (NPI), cognitive (including the proportion of subjects maintaining their decisional capacity during the study using the MacCAT-CR interview in the Netherlands) and functional performance (RBANS, CDR-SB) scores | — |
Countries
Netherlands
Outcome results
None listed