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CompletedNCT04445831Updated Feb 14, 2025Results posted

A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants With Early Alzheimer's Disease

A Phase 1/2 interventional study of ACI-35.030 and ACI-35.030 in Alzheimer's Disease, Cognitive Impairment and Tauopathies, sponsored by AC Immune SA. Completed at 9 sites in 4 countries. Open to participants aged 50 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-02-14.

Sponsored by AC Immune SA · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
57
Allocation
Randomized
Ages
50 Years to 75 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Alzheimer's Disease
  • Cognitive Impairment
  • Tauopathies
  • Mild Cognitive Impairment
  • Dementia
  • Brain Diseases
  • Central Nervous System Diseases

Keywords

  • Alzheimer's Disease
  • Cognitive Impairment
  • Tauopathies
  • Mild Cognitive Impairment
  • Dementia
  • Brain Diseases
  • Central Nervous System Diseases
03

Who can participate

Ages eligible
50 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 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.
  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.
  8. Subjects who in the opinion of the investigator is able to understand and provide written informed consent.
  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:

  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. Drug or alcohol abuse or dependence currently met or within the past five years according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria.
  11. Any clinically significant medical condition likely to interfere with the evaluation of safety and tolerability of the study treatment and/or the adherence to the full study visit schedule.
  12. Any clinically significant medical condition likely to impact the immune system (e.g, any history of acquired or innate immune system disorder).
  13. Use of hydralazine, procainamide, quinidine, isoniazide, TNF-inhibitors, minocycline within the last 12 months prior to screening.
  14. Use of diltiazem unless on a stable dose for at least 3 months prior to screening.
  15. Significant risk of suicide defined, using the Columbia-Suicide Severity Rating Scale, as the subject answering: "yes" to suicidal ideation questions 4 or 5 or answering: "yes" to suicidal behavior within the past 12 months.
  16. Concomitant psychiatric or neurologic disorder other than those considered to be related to AD.
  17. History or presence of uncontrolled seizures.
  18. History of meningoencephalitis within the past 10 years prior to screening.
  19. Subjects with a history of hemorrhagic and/or non-hemorrhagic stroke.
  20. Presence or history of peripheral neuropathy.
  21. History of inflammatory neurological disorders with potential for CNS involvement.
  22. Screening MRI scan showing structural evidence of alternative pathology not consistent with AD which could cause the subject's symptoms.
  23. MRI examination cannot be done for any reason, including but not limited to metal implants contraindicated for MRI studies and/or severe claustrophobia.
  24. Significant hearing or visual impairment or other issues judged relevant by the investigator preventing to comply with the protocol and to perform the outcome measures.
  25. Clinically significant infections or major surgical operation within 3 months prior to screening.
  26. Any vaccine received within the past 2 weeks before screening, including influenza vaccine.
  27. Clinically significant arrhythmias or other clinically significant abnormalities on ECG at screening.
  28. Myocardial infarction within one year prior to baseline, unstable angina pectoris, or significant coronary artery disease.
  29. History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in situ, or in-situ prostate cancer or in-situ breast cancer which have been fully removed and are considered cured.
  30. Clinically significant deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, that are judged to be clinically significant in the opinion of the investigator.
  31. Pregnancy confirmed by blood test at screening, or subject planning to be pregnant or lactating.
  32. Receipt of any anticoagulant drug or antiplatelet drug, except aspirin at doses of 100 mg daily or lower.
  33. Receipt of any antipsychotic drugs unless on stable low doses for the treatment of insomnia.
  34. Donation of blood or blood products within 30 days prior to screening or plans to donate blood while participating in the study.
  35. Positive Venereal Disease Research Laboratory (VDRL) consistent with active syphilis at screening.
  36. Positive HIV test at screening.
  37. Laboratory or clinical evidence of active hepatitis B and/or C at screening.
  38. Serum creatinine greater than 1.5x upper limit of normal, abnormal thyroid function tests or clinically significant reduction in serum B12 or folate levels.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
57 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Placebo administered at predefined time points over a 48-week period.

    Other: Placebo

  • Experimental
    ACI-35.030 - Low dose

    Active vaccine administered at predefined time points over a 48-week period.

    Biological: ACI-35.030

  • Experimental
    ACI-35.030 - Medium dose

    Active vaccine administered at predefined time points over a 48-week period.

    Biological: ACI-35.030

  • Experimental
    ACI-35.030 - High dose

    Active vaccine administered at predefined time points over a 48-week period.

    Biological: ACI-35.030

  • Experimental
    JACI-35.054 - Low dose

    Active vaccine administered at predefined time points over a 48-week period.

    Biological: JACI-35.054

  • Experimental
    JACI-35.054 - Medium dose

    Active vaccine administered at predefined time points over a 48-week period.

    Biological: JACI-35.054

Interventions

  • BiologicalACI-35.030

    Administration of a Low dose of ACI-35.030

  • BiologicalACI-35.030

    Administration of a Medium dose of ACI-35.030

  • BiologicalACI-35.030

    Administration of a High dose of ACI-35.030

  • OtherPlacebo

    Administration of Placebo

  • BiologicalJACI-35.054

    Administration of a Low dose of JACI-35.054

  • BiologicalJACI-35.054

    Administration of a Medium dose of JACI-35.054

05

What researchers measure

Primary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

Other outcomes

  1. Change From Baseline of Functional Performance Using CDR-SB Scale

    CDR-SB means Clinical Dementia Rating - Sum of Boxes. The score ranges from 0 to 18. A higher score indicates a worse outcome.

    Time frame: from baseline up to week 74

  2. Change From Baseline of Cognitive Performance Using RBANS Scale

    RBANS means Repeatable Battery for the Assessment of Neuropsychological Status. The total scale index score ranges from 40 to 160. A higher score indicates a better outcome.

    Time frame: from baseline up to week 74

  3. Change From Baseline of Behavior Using NPI Scale

    NPI means Neuropsychiatric Inventory. The score ranges from 0 to 144. A higher score indicates a worse outcome.

    Time frame: from baseline up to week 74

06

Results

Posted Feb 14, 2025
Limitations and caveats
* The study was not powered to detect differences between the active and placebo treatments for exploratory endpoints (e.g., fluid biomarkers and cognition/clinical efficacy outcomes). * The sub-cohort 1.1 (ACI-35.030 300 μg / placebo) was significantly impacted by the COVID-19 pandemic due to local travel restriction in Finland. Seven out of 8 subjects (5 active and 2 placebo) in this sub-cohort missed 1 study treatment administration.

Participant flow

Recruitment was performed in Finland, the Netherlands, Sweden and the UK. 79 subjects were screened for the study; 22 subjects did not meet the eligibility criteria; 1 subject was re-screened and qualified to participate.

Participant flow — Overall Study
MilestoneSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Started619610664
Completed417510664
Not completed2210000
Withdrew: Withdrawal by subject2110000
Withdrew: Subject withdrawal by caregiver0100000

Outcome measures

PrimaryOverview 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)
Reported as:
Count of participants · Participants
Overview of Treatment-Emergent Adverse Events, Safety Set
ParticipantsSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Any TEAE61768664
Any Serious TEAE2220001
Any Severe TEAE1200001
Any Adverse Drug Reactions31562420
Any Serious Adverse Drug Reactions0100000
Any TEAE Leading to Study Drug Discontinuation0000000
Any TEAE Leading to Study Discontinuation0000000
Any TEAE with Outcome of Death0000000
PrimaryOverview 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)
Reported as:
Count of participants · Participants
Overview of Treatment-Emergent Adverse Events Assessed by Intensity, Safety Set
ParticipantsSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Mild2834312
Moderate3734351
Severe1200001
PrimaryOverview 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)
Reported as:
Count of participants · Participants
Overview of Treatment-Emergent Adverse Events Assessed by Relationship to Study Drug, Safety Set
ParticipantsSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Unrelated3206244
Related31562420
PrimaryMean 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.
Reported as:
Mean · mmHg
Mean Change From Baseline in Diastolic Blood Pressure, ITT Set
mmHgSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Change from baseline to Week 26-6.00 ± NA2.47 ± 8.7903.67 ± 5.9892.00 ± 7.578-5.00 ± 3.795-3.17 ± 7.627-8.25 ± 14.500
Change from baseline to Week 50-6.75 ± 2.500-0.33 ± 6.3345.20 ± 9.203-4.20 ± 6.713-1.83 ± 5.037-2.50 ± 5.167-5.00 ± 8.602
Change from baseline to Week 74-3.75 ± 5.3774.76 ± 8.5111.60 ± 5.8570.40 ± 7.412-3.33 ± 6.947-3.33 ± 4.227-1.25 ± 11.325
PrimaryMean 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.
Reported as:
Mean · mmHg
Mean Change From Baseline in Systolic Blood Pressure, ITT Set
mmHgSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Change from baseline to Week 26-15.00 ± NA4.11 ± 16.7739.33 ± 8.3351.38 ± 11.388-3.17 ± 9.4113.50 ± 8.550-3.75 ± 27.861
Change from baseline to Week 50-5.25 ± 13.647-1.83 ± 19.2429.20 ± 9.859-2.50 ± 14.3931.33 ± 17.5350.67 ± 5.574-1.75 ± 23.243
Change from baseline to Week 74-3.75 ± 15.457-1.00 ± 19.0826.60 ± 15.421-1.60 ± 21.0350.67 ± 17.014-2.83 ± 7.1953.75 ± 27.208
PrimaryMean 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.
Reported as:
Mean · bpm
Mean Change From Baseline in Heart Rate, ITT Set
bpmSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Change from baseline to Week 26-2.00 ± NA-4.11 ± 9.225-1.17 ± 9.948-4.38 ± 11.649-1.83 ± 7.494-0.33 ± 4.885-10.00 ± 11.888
Change from baseline to Week 50-5.75 ± 4.193-2.61 ± 7.935-2.80 ± 7.596-0.30 ± 9.019-6.00 ± 5.762-3.00 ± 6.633-7.25 ± 11.558
Change from baseline to Week 742.25 ± 6.7521.41 ± 8.675-7.40 ± 7.2321.90 ± 13.674-6.17 ± 3.920-0.67 ± 7.967-10.25 ± 14.728
PrimaryMean 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.
Reported as:
Mean · °C
Mean Change From Baseline in Body Temperature, ITT Set
°CSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Change from baseline to Week 26-0.40 ± NA0.02 ± 0.6170.03 ± 0.3670.19 ± 0.3600.12 ± 0.7810.02 ± 0.4620.30 ± 0.497
Change from baseline to Week 500.03 ± 0.2990.18 ± 0.451-0.04 ± 0.5320.36 ± 0.357-0.08 ± 0.880-0.47 ± 0.2660.05 ± 0.635
Change from baseline to Week 740.08 ± 0.1710.13 ± 0.625-0.18 ± 0.3830.29 ± 0.6230.00 ± 0.555-0.35 ± 0.3670.15 ± 0.436
PrimaryNumber 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.
Reported as:
Count of participants · Participants
Number of Participants Reporting Suicidal Ideation or Behavior Using Columbia-Suicide Severity Rating Scale (C-SSRS), ITT Set
ParticipantsSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Suicidal ideation or behavior - Baseline — No619610664
Suicidal ideation or behavior - Baseline — Yes0000000
Suicidal ideation or behavior - Week 26 — No319610664
Suicidal ideation or behavior - Week 26 — Yes0000000
Suicidal ideation or behavior - Week 50 — No418510564
Suicidal ideation or behavior - Week 50 — Yes0000100
Suicidal ideation or behavior - Week 74 — No417510664
Suicidal ideation or behavior - Week 74 — Yes0000000
PrimaryNumber 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.
Reported as:
Count of participants · Participants
Number of Participants With Abnormal MRI Results, ITT Set
ParticipantsSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Baseline — Normal517610564
Baseline — Abnormal NCS1200100
Baseline — Abnormal CS0000000
Baseline — Not evaluable0000000
Week 10 — Normal616610664
Week 10 — Abnormal NCS0200000
Week 10 — Abnormal CS0000000
Week 10 — Not evaluable0100000
Week 26 — Normal11767664
Week 26 — Abnormal NCS0200000
Week 26 — Abnormal CS0000000
Week 26 — Not evaluable0001000
Week 50 — Normal417510654
Week 50 — Abnormal NCS0100010
Week 50 — Abnormal CS0000000
Week 50 — Not evaluable0000000
Week 74 — Normal315510643
Week 74 — Abnormal NCS0200021
Week 74 — Abnormal CS0000000
Week 74 — Not evaluable0000000
PrimaryAnti-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.
Reported as:
Geometric mean · AU/mL
Anti-pTau IgG Antibody Response in Serum - Antibody Titers, ITT Set
AU/mLSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Baseline2048.4 (1155.4 to 3631.6)994.6 (688.7 to 1436.5)676.2 (476.0 to 960.6)802.4 (713.5 to 902.2)913.9 (619.4 to 1348.4)1073.3 (808.9 to 1424.1)981.7 (711.2 to 1354.9)
Week 280292.0 (37517.3 to 171835.3)158154.6 (86332.2 to 289728.2)187980.6 (99157.0 to 356371.2)811.0 (714.5 to 920.5)1403.8 (1065.4 to 1849.6)5286.1 (1053.3 to 26530.2)895.4 (598.7 to 1339.2)
Week 849360.9 (19121.1 to 127424.7)92181.7 (56336.9 to 150833.0)66035.9 (37536.0 to 116174.9)768.6 (684.5 to 863.1)3054.4 (1875.2 to 4975.1)6928.5 (2386.1 to 20118.9)971.5 (668.5 to 1412.0)
Week 10110984.4 (31648.6 to 389197.3)182111.4 (113522.2 to 292141.7)135520.1 (71679.7 to 256219.1)749.7 (652.5 to 861.4)105042.6 (39205.0 to 281442.5)82513.4 (34350.2 to 198207.6)969.2 (671.7 to 1398.6)
Week 246900.0 (NA to NA)32248.7 (19704.9 to 52777.7)19853.3 (10110.8 to 38983.4)1056.1 (860.3 to 1296.6)27519.3 (11321.5 to 66891.5)27030.2 (11647.9 to 62726.3)789.4 (524.8 to 1187.3)
Week 2621800.0 (NA to NA)71385.3 (43249.5 to 117824.7)60104.8 (26253.5 to 137603.9)1136.8 (913.4 to 1414.8)329361.3 (136886.4 to 792473.2)123787.7 (85919.6 to 178345.7)919.5 (646.4 to 1308.0)
Week 368207.3 (3347.2 to 20124.4)30141.2 (17057.1 to 53261.7)19810.7 (9322.3 to 42099.2)571.6 (373.6 to 874.5)127585.6 (64839.7 to 251051.1)58190.1 (43600.4 to 77661.9)1245.1 (728.7 to 2127.6)
Week 485408.4 (2873.1 to 10181.1)17533.0 (9904.6 to 31036.7)10848.2 (4285.7 to 27459.9)676.2 (523.4 to 873.7)56549.1 (28051.0 to 113999.4)25968.2 (18637.2 to 36182.9)1137.1 (599.1 to 2158.2)
Week 5086662.7 (22301.9 to 336760.7)54164.6 (28561.9 to 102717.6)63735.9 (38946.7 to 104303.4)617.0 (464.4 to 819.7)408403.6 (273922.2 to 608908.1)137934.8 (61731.7 to 308205.1)1311.8 (750.6 to 2292.6)
Week 6714623.7 (7565.4 to 28267.4)17464.2 (8728.8 to 34941.7)10128.3 (5232.7 to 19604.1)714.1 (555.9 to 917.2)144349.8 (92815.9 to 224496.7)47764.4 (20377.3 to 111959.5)681.2 (451.3 to 1028.0)
Week 7410527.5 (6075.0 to 18243.5)15301.0 (7889.7 to 29673.9)8565.4 (3914.9 to 18740.2)719.1 (577.5 to 895.5)107038.5 (63784.9 to 179623.2)31817.4 (11556.3 to 87601.2)682.9 (468.2 to 995.9)
PrimaryAnti-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.
Reported as:
Geometric mean · AU/mL
Anti-ePHF IgG Antibody Response in Serum - Antibody Titers, ITT Set
AU/mLSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Baseline1553.4 (1116.9 to 2160.5)2515.4 (1449.4 to 4365.5)1691.8 (862.3 to 3319.3)2006.5 (1120.3 to 3593.7)2659.9 (1508.2 to 4691.1)2027.6 (1551.2 to 2650.4)2754.4 (1696.8 to 4471.2)
Week 24147.0 (1790.9 to 9602.7)8245.3 (5162.3 to 13169.5)4132.5 (2007.6 to 8506.3)2270.6 (1276.5 to 4038.9)2419.2 (1263.7 to 4631.6)2128.4 (1371.1 to 3303.9)2680.9 (1514.7 to 4745.2)
Week 84281.7 (2522.5 to 7267.8)7928.5 (5215.6 to 12052.4)3973.2 (2439.9 to 6469.9)1992.7 (1095.7 to 3624.2)2904.3 (1461.7 to 5770.6)2270.4 (1289.0 to 3999.3)2682.9 (1663.9 to 4326.0)
Week 109371.5 (3398.3 to 25843.8)17848.1 (11623.1 to 27406.9)9317.6 (5404.3 to 16064.5)2099.3 (1172.8 to 3757.7)17874.8 (8298.9 to 38500.1)13086.9 (6317.8 to 27108.8)2497.6 (1493.9 to 4175.7)
Week 242770.0 (NA to NA)9446.6 (6001.8 to 14868.6)6424.4 (2758.4 to 14962.3)2381.2 (1081.9 to 5241.0)6235.7 (3717.7 to 10459.3)5275.9 (3016.0 to 9228.9)2128.9 (923.8 to 4906.4)
Week 263890.0 (NA to NA)13142.7 (8034.0 to 21499.9)8779.5 (4383.4 to 17584.7)2488.8 (1181.0 to 5244.9)32099.1 (10656.3 to 96688.8)17640.8 (12002.0 to 25928.7)2174.3 (918.7 to 5146.0)
Week 362709.4 (2188.5 to 3354.3)12713.9 (7440.1 to 21726.0)6886.6 (2758.6 to 17191.7)2358.4 (1297.9 to 4285.5)14491.7 (6314.7 to 33257.6)10543.9 (7864.9 to 14135.6)2273.8 (1091.3 to 4737.7)
Week 482287.7 (1733.1 to 3019.9)9108.4 (5469.1 to 15169.4)5886.6 (2446.7 to 14162.3)2254.2 (1218.0 to 4171.7)7237.2 (3437.4 to 15237.7)6321.2 (4670.3 to 8555.7)2213.5 (969.2 to 5055.1)
Week 507472.5 (3323.2 to 16802.6)13280.3 (7620.5 to 23143.7)8536.0 (4170.1 to 17472.6)2340.1 (1268.6 to 4317.0)30248.2 (12315.3 to 74294.5)25491.5 (10441.9 to 62231.3)2436.9 (1199.6 to 4950.6)
Week 673219.8 (2578.6 to 4020.4)8944.8 (5974.4 to 13392.0)6180.6 (2623.0 to 14563.1)2080.4 (1122.4 to 3856.0)13077.0 (7162.9 to 23874.1)10082.0 (4602.9 to 22083.5)2295.7 (1480.2 to 3560.6)
Week 742791.9 (2285.3 to 3410.8)8993.0 (5314.7 to 15216.9)5383.9 (2349.5 to 12337.4)2126.0 (1168.7 to 3867.5)10835.5 (5870.1 to 20000.8)6788.7 (3017.2 to 15274.3)2178.8 (1549.6 to 3063.5)
SecondaryAnti-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.
Reported as:
Geometric mean · AU/mL
Anti-Tau IgG Antibody Response in Serum - Antibody Titers, ITT Set
AU/mLSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Baseline374.7 (287.3 to 488.8)357.1 (238.3 to 535.2)355.4 (125.2 to 1008.8)251.7 (198.1 to 319.7)223.0 (135.4 to 367.5)394.1 (290.2 to 535.3)261.0 (144.2 to 472.4)
Week 22609.5 (1098.9 to 6196.6)8753.9 (3767.6 to 20339.8)6549.6 (1614.8 to 26564.8)230.4 (186.1 to 285.1)744.5 (390.0 to 1421.1)2657.0 (524.4 to 13461.1)233.7 (118.9 to 459.4)
Week 81065.0 (512.3 to 2213.9)3631.9 (1709.8 to 7714.8)2000.8 (704.1 to 5685.1)243.1 (192.6 to 306.7)2564.1 (1753.4 to 3749.5)4349.6 (1372.9 to 13780.8)253.3 (132.3 to 484.9)
Week 101508.6 (649.3 to 3505.4)4217.5 (2120.6 to 8387.6)2921.6 (1391.6 to 6133.8)242.5 (208.3 to 282.4)84688.8 (36848.8 to 194638.7)46411.7 (23609.7 to 91235.4)262.8 (106.9 to 646.4)
Week 24578.0 (NA to NA)1124.8 (647.0 to 1955.5)851.6 (364.5 to 1989.6)343.3 (285.9 to 412.2)16444.7 (6570.8 to 41155.8)19762.7 (8882.8 to 43968.6)236.2 (130.0 to 429.2)
Week 26798.0 (NA to NA)1375.2 (980.6 to 1928.6)1859.0 (867.8 to 3982.4)339.5 (262.9 to 438.2)162241.1 (72817.9 to 361479.1)74795.1 (40734.0 to 137337.3)237.9 (139.4 to 406.1)
Week 36523.3 (358.4 to 764.1)828.6 (458.0 to 1499.1)806.3 (306.5 to 2121.3)240.6 (180.5 to 320.6)59209.8 (35862.2 to 97757.4)31504.2 (19187.4 to 51727.4)310.1 (170.6 to 563.7)
Week 48416.0 (279.6 to 618.9)635.2 (354.9 to 1136.9)417.1 (212.1 to 820.1)243.1 (181.6 to 325.4)25681.2 (14983.1 to 44017.8)13486.3 (7865.4 to 23124.1)282.8 (153.1 to 522.4)
Week 501023.0 (594.5 to 1760.3)1092.4 (595.6 to 2003.5)1132.9 (472.2 to 2718.2)231.8 (172.2 to 312.0)197833.5 (123950.4 to 315756.0)70122.6 (32136.3 to 153009.8)286.5 (157.2 to 522.1)
Week 67450.1 (342.4 to 591.7)551.2 (321.7 to 944.6)570.6 (329.0 to 989.6)269.6 (205.4 to 353.8)69607.0 (43695.0 to 110885.3)32158.7 (12000.4 to 86178.7)282.6 (213.5 to 374.0)
Week 74439.4 (366.2 to 527.3)590.0 (327.6 to 1062.4)571.9 (334.2 to 978.6)253.3 (172.3 to 372.5)51718.4 (30576.2 to 87479.7)21920.5 (7062.2 to 68039.9)267.4 (156.3 to 457.3)
SecondaryAnti-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.
Reported as:
Geometric mean · AU/mL
Anti-pTau IgM Antibody Response in Serum - Antibody Titers, ITT Set
AU/mLSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Baseline355.3 (162.5 to 777.0)154.8 (113.9 to 210.4)368.6 (247.9 to 547.9)297.5 (166.8 to 530.6)337.3 (190.5 to 597.4)147.1 (50.2 to 431.4)248.5 (100.0 to 617.5)
Week 225951.9 (11858.8 to 56793.5)15563.7 (10500.7 to 23067.8)20464.3 (6475.2 to 64676.0)297.5 (167.9 to 527.4)494.9 (236.3 to 1036.2)327.4 (100.9 to 1062.4)237.2 (76.6 to 734.5)
Week 83666.8 (1795.4 to 7488.6)3439.4 (2477.0 to 4775.7)4936.6 (1625.2 to 14994.8)274.9 (158.5 to 476.8)476.8 (241.0 to 943.4)276.8 (108.5 to 706.1)217.4 (76.7 to 615.9)
Week 104436.9 (2723.2 to 7229.1)4792.5 (3376.5 to 6802.3)7672.5 (3433.5 to 17144.9)288.5 (165.5 to 503.0)564.7 (266.4 to 1197.1)349.6 (139.2 to 877.8)225.5 (74.3 to 684.3)
Week 24696.0 (NA to NA)1967.4 (1598.0 to 2422.3)2758.4 (1380.1 to 5513.0)345.0 (158.5 to 750.9)473.9 (215.5 to 1042.1)202.6 (118.6 to 346.0)183.3 (66.6 to 504.3)
Week 262830.0 (NA to NA)5137.1 (3815.8 to 6916.0)7950.1 (3857.6 to 16384.4)334.8 (154.6 to 725.2)483.3 (213.7 to 1093.0)153.5 (69.1 to 341.1)181.8 (64.9 to 509.6)
Week 36806.2 (394.4 to 1647.9)2958.8 (2148.6 to 4074.6)2906.2 (1516.6 to 5569.2)308.2 (168.4 to 564.0)356.1 (204.2 to 621.2)329.0 (143.4 to 754.5)265.4 (83.0 to 848.1)
Week 48802.9 (383.6 to 1680.4)1789.3 (1318.7 to 2428.0)2362.7 (1131.0 to 4935.4)310.9 (173.0 to 558.5)368.6 (199.9 to 679.7)297.6 (91.5 to 967.3)278.1 (84.2 to 919.0)
Week 504714.6 (1996.9 to 11131.2)5214.3 (3348.3 to 8120.3)8509.3 (3839.7 to 18857.4)318.9 (174.9 to 581.1)360.5 (215.5 to 603.1)248.8 (92.0 to 672.8)275.0 (84.3 to 897.1)
Week 671858.5 (879.0 to 3929.7)1898.6 (1275.1 to 2827.0)4539.9 (2155.0 to 9564.3)431.9 (233.9 to 797.3)393.7 (199.1 to 778.7)240.5 (73.6 to 785.3)186.7 (57.9 to 602.1)
Week 741785.9 (801.8 to 3977.8)1509.7 (1063.2 to 2143.7)3880.2 (1741.4 to 8645.9)343.0 (191.9 to 613.3)449.9 (248.2 to 815.4)252.9 (75.6 to 845.9)348.0 (79.0 to 1533.3)
SecondaryAnti-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.
Reported as:
Geometric mean · AU/mL
Anti-Tau IgM Antibody Response in Serum - Antibody Titers, ITT Set
AU/mLSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Baseline153.0 (69.6 to 336.2)93.1 (66.8 to 129.6)124.4 (64.0 to 241.9)108.1 (73.4 to 159.2)93.7 (42.9 to 204.8)94.6 (36.6 to 244.7)119.3 (44.3 to 321.4)
Week 2460.7 (185.3 to 1145.2)449.8 (222.5 to 909.6)737.8 (121.6 to 4478.3)105.4 (70.0 to 158.6)146.1 (56.5 to 378.0)139.6 (48.2 to 404.2)129.9 (43.7 to 386.3)
Week 8228.3 (107.3 to 485.6)209.6 (127.3 to 345.0)333.4 (72.0 to 1543.1)98.2 (67.3 to 143.5)116.8 (53.7 to 253.8)101.3 (38.4 to 267.2)116.5 (44.1 to 307.8)
Week 10220.8 (135.4 to 360.0)209.5 (133.8 to 328.0)409.5 (127.0 to 1320.6)101.3 (68.9 to 148.8)119.2 (54.3 to 261.3)123.2 (46.5 to 326.2)117.4 (43.6 to 316.0)
Week 24231.0 (NA to NA)134.2 (98.3 to 183.0)181.2 (75.1 to 437.3)90.2 (63.3 to 128.5)100.8 (51.3 to 198.2)102.3 (46.0 to 227.6)104.1 (40.1 to 270.4)
Week 26256.0 (NA to NA)198.8 (158.9 to 248.7)286.2 (136.2 to 601.6)87.2 (57.4 to 132.5)107.9 (53.3 to 218.8)105.9 (48.0 to 233.8)103.3 (40.8 to 261.4)
Week 3695.2 (51.2 to 177.0)264.6 (198.1 to 353.3)476.7 (282.4 to 804.7)107.7 (61.5 to 188.7)101.1 (51.4 to 198.9)100.1 (37.2 to 268.9)147.4 (58.1 to 373.9)
Week 48111.6 (43.0 to 289.6)232.9 (178.6 to 303.8)468.3 (191.5 to 1145.1)120.9 (70.7 to 206.9)125.8 (67.3 to 235.1)133.4 (45.6 to 390.7)162.6 (62.6 to 422.4)
Week 50171.9 (74.8 to 395.0)349.2 (270.4 to 450.9)507.4 (227.5 to 1131.9)108.3 (61.3 to 191.2)102.4 (52.2 to 201.0)110.1 (44.3 to 274.1)164.9 (65.0 to 418.2)
Week 67147.8 (61.5 to 355.0)202.7 (142.6 to 288.0)342.5 (116.4 to 1007.7)109.7 (70.9 to 169.6)93.1 (43.0 to 201.5)130.9 (49.2 to 348.2)144.9 (54.7 to 384.0)
Week 74144.1 (43.4 to 478.7)169.1 (121.8 to 234.6)329.9 (111.9 to 972.3)128.2 (90.0 to 182.6)108.4 (51.4 to 228.6)130.6 (49.2 to 346.3)161.8 (58.5 to 447.2)
Other pre-specifiedChange From Baseline of Functional Performance Using CDR-SB Scale

CDR-SB means Clinical Dementia Rating - Sum of Boxes. The score ranges from 0 to 18. A higher score indicates a worse outcome.

Time frame:
from baseline up to week 74

Results for this outcome have not been posted.

Other pre-specifiedChange From Baseline of Cognitive Performance Using RBANS Scale

RBANS means Repeatable Battery for the Assessment of Neuropsychological Status. The total scale index score ranges from 40 to 160. A higher score indicates a better outcome.

Time frame:
from baseline up to week 74

Results for this outcome have not been posted.

Other pre-specifiedChange From Baseline of Behavior Using NPI Scale

NPI means Neuropsychiatric Inventory. The score ranges from 0 to 144. A higher score indicates a worse outcome.

Time frame:
from baseline up to week 74

Results for this outcome have not been posted.

Adverse events

Collected over The safety reporting period covering any Adverse Events which were treatment-emergent is the interval between the first dosing (Visit 1, Week 0) and the last safety follow-up visit (Visit 11, Week 74); up to 74 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sub-Cohort 1.1 (ACI-35.030 300 μg)0/6 (0%)2/6 (33.3%)6/6 (100%)
Sub-Cohort 1.2 (ACI-35.030 900 μg)0/19 (0%)2/19 (10.5%)17/19 (89.5%)
Sub-Cohort 1.3 (ACI-35.030 1800 μg)0/6 (0%)2/6 (33.3%)6/6 (100%)
Cohort 1 Placebo0/10 (0%)0/10 (0%)8/10 (80%)
Sub-Cohort 2.1 (JACI-35.054 15 μg)0/6 (0%)0/6 (0%)6/6 (100%)
Sub-Cohort 2.2 (JACI-35.054 60 μg)0/6 (0%)0/6 (0%)6/6 (100%)
Cohort 2 Placebo0/4 (0%)1/4 (25%)4/4 (100%)
Most frequent serious events
Most frequent serious events
EventSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders0/60/190/60/100/60/61/4
DiverticulitisInfections and infestations1/60/190/60/100/60/60/4
Sinus node dysfunctionCardiac disorders1/60/190/60/100/60/60/4
DiverticulumGastrointestinal disorders0/60/191/60/100/60/60/4
Aneurysm thrombosisVascular disorders0/60/191/60/100/60/60/4
Peripheral artery aneurysmVascular disorders0/60/191/60/100/60/60/4
Haemorrhagic fever with renal syndromeInfections and infestations0/61/190/60/100/60/60/4
Injection site rashGeneral disorders0/61/190/60/100/60/60/4
Post-traumatic painInjury, poisoning and procedural complications0/61/190/60/100/60/60/4
DizzinessNervous system disorders0/61/190/60/100/60/60/4
Most frequent other events
Showing 10 of 116
Most frequent other events
EventSub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 Placebo
Injection site reactionGeneral disorders2/614/196/60/101/62/60/4
PyrexiaGeneral disorders1/63/191/60/103/60/60/4
NasopharyngitisInfections and infestations3/62/191/61/100/61/61/4
HeadacheNervous system disorders0/64/193/60/102/61/61/4
COVID-19Infections and infestations0/67/192/63/101/60/61/4
MalaiseGeneral disorders0/62/190/60/102/61/60/4
MyalgiaMusculoskeletal and connective tissue disorders0/60/190/60/102/60/60/4
EpistaxisRespiratory, thoracic and mediastinal disorders0/62/190/60/102/60/60/4
Ventricular extrasystolesCardiac disorders0/60/190/60/102/60/60/4
Urinary tract infectionInfections and infestations0/60/190/61/100/60/61/4

Baseline characteristics

The data of the 57 subjects who have been randomized in the study (e.g. signed the consent, eligible and received at east 1 administration of the study drug) have been considered

Age, Categorical
Age, Categorical(Participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
<=18 years00000000
Between 18 and 65 years362215120
>=65 years3134851337
Age, Continuous
Age, Continuous(years)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
Mean65.5 ± 5.0168.0 ± 6.2964.7 ± 4.6367.7 ± 4.6066.7 ± 6.2263.0 ± 4.7768.0 ± 6.1666.67 ± 5.54
Sex: Female, Male
Sex: Female, Male(Participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
Female492533430
Male2104533027
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
Hispanic or Latino00000000
Not Hispanic or Latino61861066456
Unknown or Not Reported01000001
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
American Indian or Alaska Native00000000
Asian00000000
Native Hawaiian or Other Pacific Islander00000000
Black or African American00000000
White61961066457
More than one race00000000
Unknown or Not Reported00000000
Region of Enrollment
Region of Enrollment(participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
Netherlands062231014
Sweden04010106
Finland662734432
United Kingdom03200005
Clinical Dementia Rating (CDR) - Global Score
Clinical Dementia Rating (CDR) - Global Score(Participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
Score = 0.56175865350
Score = 102120117
Concomitant Medication
Concomitant Medication(Participants)Sub-Cohort 1.1 (ACI-35.030 300 μg)Sub-Cohort 1.2 (ACI-35.030 900 μg)Sub-Cohort 1.3 (ACI-35.030 1800 μg)Cohort 1 PlaceboSub-Cohort 2.1 (JACI-35.054 15 μg)Sub-Cohort 2.2 (JACI-35.054 60 μg)Cohort 2 PlaceboTotal
Acetylcholinesterase Inhibitors and/or Memantine5145835444
No Acetylcholinesterase Inhibitors or Memantine151231013

1 further baseline measures are reported on the registry.

07

Study locations

9 sites
  • 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
08

References and documents

Study documents

  • Study protocol · Oct 22, 2021
  • Statistical analysis plan · Dec 5, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Individual participant data (IPD) are not planned to be shared for this early-phase non-pivotal ACI-35-1802 Phase 1b/2a study. However, group-level data may be shared to qualified researchers who engage in rigorous independent scientific research after the review and approval of a proposal sent to the sponsor (see Contacts) and the execution of a data sharing agreement. In addition, the Clinical Study Protocol and the Statistical Plan will be available in this registry once the study results are released.

09

Registry details

Key details

Study ID
NCT04445831
Lead sponsor
AC Immune SA
Collaborators
Janssen Research & Development, LLC
Responsible party
Sponsor
First posted
Jun 24, 2020
Start date
Jul 31, 2019
Primary completion
Sep 5, 2023
Completion
Sep 5, 2023
Results posted
Feb 14, 2025
Last update
Feb 14, 2025

Study contacts

Philip Scheltens, MD
principal investigator · Amsterdam UMC Alzheimer Center de Boelelaan Amsterdam The Netherlands

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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