This study is a multicenter, double blind, randomized, placebo-controlled study to evaluate the safety, tolerability and immunogenicity of different doses, regimens and combinations of Tau targeted vaccines in participants with early Alzheimer's Disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
57
Administration of a Low dose of ACI-35.030
Administration of a Medium dose of ACI-35.030
Administration of a High dose of ACI-35.030
Administration of Placebo
Administration of a Low dose of JACI-35.054
Administration of a Medium dose of JACI-35.054
Clinical Research Services Helsinki
Helsinki, Finland
Itä-Suomen Yliopisto - Kuopion Kampus
Kuopio, Finland
Clinical Research Services Turku
Turku, Finland
Brain Research Center - Den Bosch
's-Hertogenbosch, Netherlands
Brain Research Center - Amsterdam
Amsterdam, Netherlands
Minnesmottagningen - Sahlgrenska Universitetssjukhuset - Mölndal Sjukhus
Mölndal, Sweden
Kognitiv Mottagning - Karolinska Universitetssjukhuset - Huddinge
Stockholm, Sweden
Edinburgh Clinical Research Facility
Edinburgh, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Overview of Treatment-Emergent Adverse Events, Safety Set
Categorical data are presented with the number of subjects with at least one event for the defined categories. Subjects are included only once, even if they experienced multiple events in a category.
Time frame: AEs falling between first dosing (week 0) and last study visit (week 74), ie up to 74 weeks, defined as Treatment-Emergent Adverse Events (TEAEs)
Overview of Treatment-Emergent Adverse Events Assessed by Intensity, Safety Set
Categorical data are presented with the number of subjects with at least one Treatment-Emergent Adverse Event (TEAE) assessed as: * Mild: Easily tolerated and causes minimal discomfort and does not interfere with everyday activities. * Moderate: Sufficiently discomforting to interfere with normal everyday activities; intervention may be needed. Event is not hazardous to the subject's health * Severe: Prevents normal everyday activities; treatment or other intervention usually needed. Hazard to the subject's health Although subjects may have experienced multiple events, they are included only once, in the maximum severity category
Time frame: Between the first dosing and the last study visit (week 74)
Overview of Treatment-Emergent Adverse Events Assessed by Relationship to Study Drug, Safety Set
Categorical data are presented with the number of subjects with at least one Treatment-Emergent Adverse Event (TEAE) assessed as: * Unrelated: Events reported as unrelated or unlikely related to study drug * Related: Events reported as possibly related or probably related to study drug Although subjects may have experienced multiple events, they are included only once, in the strongest relationship category
Time frame: Between the first dosing and the last study visit (week 74)
Mean Change From Baseline in Diastolic Blood Pressure, ITT Set
At reported visits, diastolic blood pressures (mmHg = millimeter of mercury) were measured in sitting position only, after the subject has been sitting down for at least 5 minutes. A change from baseline value is defined as the value at post-baseline timepoint minus the baseline value, i.e. post-baseline value - baseline value
Time frame: Endpoint is assessed from baseline (i.e. last non-missing value prior to the first immunization at week 0) to the last study visit (week 74), at weeks 26, 50 and 74.
Mean Change From Baseline in Systolic Blood Pressure, ITT Set
At reported visits, systolic blood pressures (mmHg = millimeter of mercury) were measured in sitting position only, after the subject has been sitting down for at least 5 minutes. A change from baseline value is defined as the value at post-baseline timepoint minus the baseline value, i.e. post-baseline value - baseline value
Time frame: Endpoint is assessed from baseline (i.e. last non-missing value prior to the first immunization at week 0) to the last study visit (week 74), at weeks 26, 50 and 74.
Mean Change From Baseline in Heart Rate, ITT Set
At reported visits, heart rates (bpm = beats per minute) were measured in sitting position only, after the subject has been sitting down for at least 5 minutes. A change from baseline value is defined as the value at post-baseline timepoint minus the baseline value, i.e. post-baseline value - baseline value
Time frame: Endpoint is assessed from baseline (i.e. last non-missing value prior to the first immunization at week 0) to the last study visit (week 74), at weeks 26, 50 and 74.
Mean Change From Baseline in Body Temperature, ITT Set
At reported visits, body temperatures (°C = degree Celsius) were measured. A change from baseline value is defined as the value at post-baseline timepoint minus the baseline value, i.e. post-baseline value - baseline value
Time frame: Endpoint is assessed from baseline (i.e. last non-missing value prior to the first immunization at week 0) to the last study visit (week 74), at weeks 26, 50 and 74.
Number of Participants Reporting Suicidal Ideation or Behavior Using Columbia-Suicide Severity Rating Scale (C-SSRS), ITT Set
Suicidal ideation or behavior using Columbia-Suicide Severity Rating Scale (C-SSRS) was assessed at Baseline (screening or visit 1 (Week 0)) and at weeks 26, 50 and 74. A set of questions related to suicidal behavior or ideation was directly asked by the rater to the subject.
Time frame: Endpoint is assessed from baseline (i.e. last non-missing value prior to the first immunization at Visit 1 (Week 0) or Screening) to the last study visit (week 74), at weeks 26, 50 and 74.
Number of Participants With Abnormal MRI Results, ITT Set
Brain MRI scans were conducted according to the schedule of assessments, i.e. at Baseline (screening) and at weeks 10, 26, 50, 74 and examined for evidence of brain pathology. Normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) results as interpreted by the clinical site are reported.
Time frame: Endpoint is assessed from baseline (screening) to the last study visit (week 74), at weeks 10, 26, 50 and 74.
Anti-pTau IgG Antibody Response in Serum - Antibody Titers, ITT Set
At all visits, blood was collected for the determination of the immune response in serum. Anti-phosphorylated Tau (pTau) IgG titers were measured by Meso Scale Discovery (MSD). For each visit, the geometric means (AU/mL) and 95% Confidence Interval (CI) is given.
Time frame: Endpoint is assessed from baseline (i.e. mean of the titers measured at the screening and visit 1 before the first study drug administration) to the last study visit (week 74), at weeks 0, 2, 8, 10, 24, 26, 36, 48, 50, 67 and 74.
Anti-ePHF IgG Antibody Response in Serum - Antibody Titers, ITT Set
At all visits, blood was collected for the determination of the immune response in serum. Anti-enriched paired helical filaments (ePHF) IgG titers were measured by Meso Scale Discovery (MSD). For each visit, the geometric means (AU/mL) and 95% Confidence Interval (CI) is given.
Time frame: Endpoint is assessed from baseline (i.e. mean of the titers measured at the screening and visit 1 before the first study drug administration) to the last study visit (week 74), at weeks 0, 2, 8, 10, 24, 26, 36, 48, 50, 67 and 74.
Anti-Tau IgG Antibody Response in Serum - Antibody Titers, ITT Set
At all visits, blood was collected for the determination of the immune response in serum. Anti-Tau IgG titers were measured by Meso Scale Discovery (MSD). For each visit, the geometric means (AU/mL) and 95% Confidence Interval (CI) is given.
Time frame: Endpoint is assessed from baseline (i.e. mean of the titers measured at the screening and visit 1 before the first study drug administration) to the last study visit (week 74), at weeks 0, 2, 8, 10, 24, 26, 36, 48, 50, 67 and 74.
Anti-pTau IgM Antibody Response in Serum - Antibody Titers, ITT Set
At all visits, blood was collected for the determination of the immune response in serum. Anti-phosphorylated Tau (pTau) IgM titers were measured by enzyme-linked immunosorbent assay (ELISA). For each visit, the geometric means (AU/mL) and 95% Confidence Interval (CI) is given.
Time frame: Endpoint is assessed from baseline (i.e. mean of the titers measured at the screening and visit 1 before the first study drug administration) to the last study visit (week 74), at weeks 0, 2, 8, 10, 24, 26, 36, 48, 50, 67 and 74.
Anti-Tau IgM Antibody Response in Serum - Antibody Titers, ITT Set
At all visits, blood was collected for the determination of the immune response in serum. Anti-Tau IgM titers were measured by enzyme-linked immunosorbent assay (ELISA). For each visit, the geometric means (AU/mL) and 95% Confidence Interval (CI) is given.
Time frame: Endpoint is assessed from baseline (i.e. mean of the titers measured at the screening and visit 1 before the first study drug administration) to the last study visit (week 74), at weeks 0, 2, 8, 10, 24, 26, 36, 48, 50, 67 and 74.
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