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    Clinical Trial Results:
    A Phase II Double-Blind, Randomized, Placebo-Controlled, Adaptive Design Study to Assess the Safety, Tolerability, Immunogenicity and Target Engagement of ACI-24 Formulations in Patients with Mild Alzheimer’s Disease

    Summary
    EudraCT number
    2018-000445-39
    Trial protocol
    FI   SE   GB  
    Global end of trial date
    12 Mar 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    25 Mar 2022
    First version publication date
    25 Mar 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ACI-24-1801
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AC Immune SA
    Sponsor organisation address
    EPFL Innocation Park, Building B, Lausanne, Switzerland, 1015
    Public contact
    Clinical Trial Information, AC Immune SA, +41 213459121, clinicaltrials@acimmune.com
    Scientific contact
    Clinical Trial Information, AC Immune SA, +41 213459121, clinicaltrials@acimmune.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Aug 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Mar 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Mar 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary Study Objective: To assess the safety and tolerability of the ACI-24 in patients with mild Alzheimer’s disease (AD). To assess the effects of ACI-24 on induction of anti-Aβ antibody responses in serum. To assess the effects of ACI-24 on brain amyloid load in patients with mild Alzheimer’s disease, assessed by florbetaben-PET imaging at 52 weeks (12 months) and 76 weeks (18 months). Secondary Study Objective: To explore the effects of ACI-24 on putative biomarkers of the progression of AD as Aβ 1-40 and Aβ 1-42 levels in CSF.
    Protection of trial subjects
    Before undertaking any study-related procedures with subjects, the purpose and nature of the study as well as possible adverse effects were explained to the subject and their caregiver, if appropriate, in understandable terms, and written informed consent was obtained from each study subject. Each informed consent form was appropriately signed and dated by the subject/caregiver and the person obtaining consent. Subject safety in general was to be monitored by the independent Data and Safety Monitoring Board (DSMB) of the study. The DSMB consisted of specific experts in the field, who met on a regular basis to review the safety data of the subjects. Details of responsibilities and activities were described in a charter. The outcome of the DSMB meeting was registered in minutes and included a recommendation as to whether to continue the study as planned or to modify or stop the study. For individual trial subjects and in addition to continous safety checks by the investigator, subjects were asked to stay on days when the study drug is administered in the clinic for at least one hour after the dose for safety reasons.  For subjects, who withdraw from the study, a final safety check at the trial site was recommended.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Finland: 9
    Country: Number of subjects enrolled
    Poland: 2
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    United Kingdom: 9
    Worldwide total number of subjects
    21
    EEA total number of subjects
    12
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    5
    From 65 to 84 years
    16
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Recruitment was performed in UK, Finland, Poland and Sweden. Fifty-four subjects were screened for the study; 33 subjects did not meet the eligibility criteria; 2 subjects were re-screened and qualified to participate.

    Pre-assignment
    Screening details
    Subjects between 50 and 85 years at screening and providing a written informed consent with a positive Florbetaben-PET scan at Screening consistent with the presence of amyloid pathology and fulfilling all further inclusion criteria could enter the clinical trial.

    Period 1
    Period 1 title
    Phase 2 - treatment (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer
    Blinding implementation details
    The study was blinded to subjects, caregivers, Sponsor, and site personnel. The Principal Investigator (PI) was provided with the site specific unblinded list after data lock. Database lock was performed at a dose-cohort level. It was the PIs’ responsibility to decide if this information should or should not be shared with the subjects. In order to remain blinded, raters who performed the cognitive tests did not have access to any clinical assessment data (eg, clinical rating scales, AEs).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment
    Arm description
    Subjects receiving 8 doses of ACI-24 (week 0, 4, 8, 12, 24, 36, 48 and 74)
    Arm type
    Experimental

    Investigational medicinal product name
    ACI-24
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intramuscular use
    Dosage and administration details
    8 doses of ACI-24 at 1000 µg/dose were tested using the Intramuscular route of administration at weeks 0, 4, 8, 12, 24, 36, 48 and 74.

    Arm title
    Placebo
    Arm description
    Subjects receiving 8 doses of Placebo (week 0, 4, 8, 12, 24, 36, 48 and 74).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Placebo consisted of a suspension of empty ACI-24 liposomes. Placebo was administered by the intramuscular route (week 0, 4, 8, 12, 24, 36, 48 and 74).

    Number of subjects in period 1
    Treatment Placebo
    Started
    14
    7
    Completed
    11
    5
    Not completed
    3
    2
         Adverse event, non-fatal
    1
    1
         Consent withdrawn by subject
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment
    Reporting group description
    Subjects receiving 8 doses of ACI-24 (week 0, 4, 8, 12, 24, 36, 48 and 74)

    Reporting group title
    Placebo
    Reporting group description
    Subjects receiving 8 doses of Placebo (week 0, 4, 8, 12, 24, 36, 48 and 74).

    Reporting group values
    Treatment Placebo Total
    Number of subjects
    14 7 21
    Age categorical
    Age greater than or equal to 50 and less than or equal to 85 years.
    Units: Subjects
        Adults (18-64 years)
    3 2 5
        From 65-84 years
    11 5 16
    Gender categorical
    Units: Subjects
        Female
    6 5 11
        Male
    8 2 10
    Subject analysis sets

    Subject analysis set title
    Randomized Set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The Randomized Set was used to describe all randomized subjects whether or not they received study drug

    Subject analysis set title
    Intention-to-Treat (ITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    The ITT Set was defined as all randomized subjects who received at least 1 dose of the study drug.

    Subject analysis set title
    Per-Protocol Analysis Set (PPS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The PPS was a subset of the ITT that included subjects who completed Week 76 and did not have any major protocol deviation, ie, deviations that would affect the evaluation of the primary objectives of the study.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The Safety Analysis Set included all randomized subjects who received at least 1 dose of the drug during the study. The Safety Analysis Set, used for analysis of safety data, was identical to the ITT Analysis Set.

    Subject analysis sets values
    Randomized Set Intention-to-Treat (ITT) Per-Protocol Analysis Set (PPS) Safety Analysis Set
    Number of subjects
    21
    21
    14
    21
    Age categorical
    Age greater than or equal to 50 and less than or equal to 85 years.
    Units: Subjects
        Adults (18-64 years)
    5
    5
    3
    5
        From 65-84 years
    16
    16
    11
    16
    Age continuous
    Units:
        
    ±
    ±
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    11
    11
    8
    11
        Male
    10
    10
    6
    10

    End points

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    End points reporting groups
    Reporting group title
    Treatment
    Reporting group description
    Subjects receiving 8 doses of ACI-24 (week 0, 4, 8, 12, 24, 36, 48 and 74)

    Reporting group title
    Placebo
    Reporting group description
    Subjects receiving 8 doses of Placebo (week 0, 4, 8, 12, 24, 36, 48 and 74).

    Subject analysis set title
    Randomized Set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The Randomized Set was used to describe all randomized subjects whether or not they received study drug

    Subject analysis set title
    Intention-to-Treat (ITT)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    The ITT Set was defined as all randomized subjects who received at least 1 dose of the study drug.

    Subject analysis set title
    Per-Protocol Analysis Set (PPS)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    The PPS was a subset of the ITT that included subjects who completed Week 76 and did not have any major protocol deviation, ie, deviations that would affect the evaluation of the primary objectives of the study.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The Safety Analysis Set included all randomized subjects who received at least 1 dose of the drug during the study. The Safety Analysis Set, used for analysis of safety data, was identical to the ITT Analysis Set.

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [1]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL) - change from baseline at week 52
    End point type
    Primary
    End point timeframe
    Baseline - Week 52
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    8
    3
    Units: AU/ml
        arithmetic mean (standard deviation)
    -17.25 ± 54.681
    -22.17 ± 38.394
    No statistical analyses for this end point

    Primary: Overview of Adverse Events, Safety analyses set

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    End point title
    Overview of Adverse Events, Safety analyses set [2]
    End point description
    Safety analyses set: All AEs and AEs related to global assessment of tolerability; physical and neurological examination results; vital signs; suicidal ideation/behavior; MRI results; electrocardiogram (ECG); routine hematology and biochemistry evaluation in blood and urine; inflammatory markers in blood and CSF. The table shows number of subjects, who were affected by the respective adverse events.
    End point type
    Primary
    End point timeframe
    Visit 1 until end of study participation of each individual subject
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    7
    Units: number of respective results
        Any AE
    14
    7
        Any treatment-related AE
    4
    1
        Any severe AE
    1
    0
        Any serious AE
    3
    2
        Any AE leading to study drug discontinuation
    1
    1
        Any AE leading to early termination
    1
    1
        Any serious treatment-related AE
    0
    0
        Any treat.-rel. AE lead. to study drug disc.
    0
    0
        Any treat.-rel. AE lead. to early termination
    0
    0
        Any AE leading to death
    0
    0
    Attachments
    Untitled (Filename: ACI-24-1801_CSR_Table_14.3.1.1.pdf)
    Untitled (Filename: ACI-24-1801_CSR_Tables_14.3.1.2-4.pdf)
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [3]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL) - change from baseline at week 2
    End point type
    Primary
    End point timeframe
    Baseline - Week 2
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    7
    Units: AU/ml
        arithmetic mean (standard deviation)
    -13.5 ± 45.698
    36.86 ± 93.698
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [4]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 4
    End point type
    Primary
    End point timeframe
    Baseline - Week 4
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    -4.79 ± 40.794
    9.83 ± 40.881
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [5]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change week 6 - baseline
    End point type
    Primary
    End point timeframe
    Baseline - week 6
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    -15.36 ± 41.715
    -4.33 ± 22.520
    No statistical analyses for this end point

    Primary: Effects of ACI-24 induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 induction of anti-Aβ antibody responses in serum [6]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 8
    End point type
    Primary
    End point timeframe
    Baseline - week 8
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    -12.43 ± 28.149
    7.0 ± 24.538
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [7]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 10
    End point type
    Primary
    End point timeframe
    Baseline - Week 10
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.93 ± 46.425
    -9.00 ± 15.807
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [8]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 12
    End point type
    Primary
    End point timeframe
    Baseline - Week 12
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    -9.29 ± 25.150
    -10.00 ± 76.389
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [9]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 14
    End point type
    Primary
    End point timeframe
    Baseline - Week 14
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    10.58 ± 38.195
    -2.10 ± 15.299
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [10]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 24
    End point type
    Primary
    End point timeframe
    Baseline - Week 24
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -13.77 ± 44.965
    20.30 ± 40.724
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [11]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 26
    End point type
    Primary
    End point timeframe
    Baseline - Week 26
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -12.31 ± 28.724
    6.50 ± 51.118
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [12]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 36
    End point type
    Primary
    End point timeframe
    Baseline - Week 36
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -24.46 ± 37.852
    -5.90 ± 24.527
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [13]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 38
    End point type
    Primary
    End point timeframe
    Baseline - Week 38
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -27.62 ± 45.864
    -1.50 ± 11.325
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [14]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 48
    End point type
    Primary
    End point timeframe
    Basline - Week 48
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    12
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -29.42 ± 42.708
    -7.90 ± 25.560
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [15]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 74
    End point type
    Primary
    End point timeframe
    Baseline - Week 74
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    11
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -35.41 ± 62.756
    -18.10 ± 67.802
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [16]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 76
    End point type
    Primary
    End point timeframe
    Baseline - Week 76
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    11
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -23.32 ± 32.709
    -9.10 ± 34.667
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [17]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 87
    End point type
    Primary
    End point timeframe
    Baseline - Week 87
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    10
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -13.45 ± 27.343
    7.70 ± 60.151
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [18]
    End point description
    For Intention-to-treat (ITT) analysis set: MSD Free Anti-Abeta1-42 IgG, Serum (AU/mL); change from baseline at week 100
    End point type
    Primary
    End point timeframe
    Baseline - Week 100
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    7
    3
    Units: AU/ml
        arithmetic mean (standard deviation)
    16.93 ± 114.113
    -23.50 ± 40.703
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [19]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 2
    End point type
    Primary
    End point timeframe
    Baseline - Week 2
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    7
    Units: AU/ml
        arithmetic mean (standard deviation)
    1.701 ± 3.359
    0.429 ± 0.847
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [20]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 4
    End point type
    Primary
    End point timeframe
    Baseline - Week 4
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.761 ± 1.575
    -0.144 ± 0.318
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [21]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 6
    End point type
    Primary
    End point timeframe
    Baseline - Week 6
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.477 ± 0.946
    -0.284 ± 0.530
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [22]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 8
    End point type
    Primary
    End point timeframe
    Baseline - Week 8
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.391 ± 0.671
    0.136 ± 0.289
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [23]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 10
    End point type
    Primary
    End point timeframe
    Baseline - Week 10
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.531 ± 1.057
    -0.099 ± 0.589
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [24]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 12
    End point type
    Primary
    End point timeframe
    Baseline - Week 12
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    6
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.050 ± 0.732
    -0.147 ± 0.341
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [25]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 14
    End point type
    Primary
    End point timeframe
    Baseline - Week 14
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.179 ± 0.481
    0.105 ± 0.146
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [26]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 24
    End point type
    Primary
    End point timeframe
    Baseline - Week 24
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.804 ± 2.542
    0.239 ± 0.558
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [27]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 26
    End point type
    Primary
    End point timeframe
    Baseline - Week 26
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    1.596 ± 3.459
    0.089 ± 0.681
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [28]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 36
    End point type
    Primary
    End point timeframe
    Baseline - week 36
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.338 ± 0.787
    -0.500 ± 0.254
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [29]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 38
    End point type
    Primary
    End point timeframe
    Baseline - Week 38
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    13
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.117 ± 1.161
    -0.636 ± 0.486
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [30]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 48
    End point type
    Primary
    End point timeframe
    Baseline - Week 48
    Notes
    [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    12
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.625 ± 0.581
    -0.590 ± 0.409
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [31]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 52
    End point type
    Primary
    End point timeframe
    Baseline- Week 52
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    8
    3
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.517 ± 0.730
    -0.711 ± 0.775
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [32]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 74
    End point type
    Primary
    End point timeframe
    Baseline - Week 74
    Notes
    [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    11
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.760 ± 0.606
    -1.198 ± 1.461
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [33]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 76
    End point type
    Primary
    End point timeframe
    Baseline - Week 76
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    11
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    0.309 ± 3.090
    -1.142 ± 1.410
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [34]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 87
    End point type
    Primary
    End point timeframe
    Baseline - Week 87
    Notes
    [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    11
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.626 ± 0.657
    -0.763 ± 0.937
    No statistical analyses for this end point

    Primary: Effects of ACI-24 on induction of anti-Aβ antibody responses in serum

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    End point title
    Effects of ACI-24 on induction of anti-Aβ antibody responses in serum [35]
    End point description
    For Intention-to-treat (ITT) analysis set: Anti-Abeta1-42 IgM, Serum (AU/mL); change from baseline at week 100
    End point type
    Primary
    End point timeframe
    Baseline - Week 100
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    11
    5
    Units: AU/ml
        arithmetic mean (standard deviation)
    -0.741 ± 0.451
    -0.795 ± 0.715
    No statistical analyses for this end point

    Primary: Effects on Mean Composite SUVR: Brain Amyloid Beta Load Assessed by PET Amyloid at baseline, 52 Weeks (12 months) and 76 Weeks (18 months)

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    End point title
    Effects on Mean Composite SUVR: Brain Amyloid Beta Load Assessed by PET Amyloid at baseline, 52 Weeks (12 months) and 76 Weeks (18 months) [36]
    End point description
    For Intention-to-treat (ITT) analysis set: Mean Composite SUVR - Actual values at baseline
    End point type
    Primary
    End point timeframe
    Baseline
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    14
    7
    Units: SUVR
        arithmetic mean (standard deviation)
    1.834 ± 0.227
    1.881 ± 0.296
    No statistical analyses for this end point

    Primary: Effects on Mean Composite SUVR: Brain Amyloid Beta Load Assessed by PET Amyloid at baseline, 52 Weeks (12 months) and 76 Weeks (18 months)

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    End point title
    Effects on Mean Composite SUVR: Brain Amyloid Beta Load Assessed by PET Amyloid at baseline, 52 Weeks (12 months) and 76 Weeks (18 months) [37]
    End point description
    For Intention-to-treat (ITT) analysis set: Mean Composite SUVR - Actual values at week 52
    End point type
    Primary
    End point timeframe
    Week 52
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    10
    3
    Units: SUVR
        arithmetic mean (standard deviation)
    1.860 ± 0.290
    1.833 ± 0.199
    No statistical analyses for this end point

    Primary: Effects on Mean Composite SUVR: Brain Amyloid Beta Load Assessed by PET Amyloid at baseline, 52 Weeks (12 months) and 76 Weeks (18 months)

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    End point title
    Effects on Mean Composite SUVR: Brain Amyloid Beta Load Assessed by PET Amyloid at baseline, 52 Weeks (12 months) and 76 Weeks (18 months) [38]
    End point description
    For Intention-to-treat (ITT) analysis set: Mean Composite SUVR - Actual values at week 76
    End point type
    Primary
    End point timeframe
    Week 76
    Notes
    [38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis were performed with no specific hypothesis
    End point values
    Treatment Placebo
    Number of subjects analysed
    10
    5
    Units: SUVR
        arithmetic mean (standard deviation)
    1.848 ± 0.203
    1.926 ± 0.237
    No statistical analyses for this end point

    Secondary: Change from Baseline of Amyloid Beta 1-40 levels in CSF

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    End point title
    Change from Baseline of Amyloid Beta 1-40 levels in CSF
    End point description
    For Intention-to-treat (ITT) analysis set: Amyloid Beta levels 1-40 - change from baseline at week 52
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    Treatment Placebo
    Number of subjects analysed
    6
    3
    Units: ng/L
        arithmetic mean (standard deviation)
    377.2 ± 442.2
    -189.7 ± 361.5
    No statistical analyses for this end point

    Secondary: Change from Baseline of Amyloid Beta 1-40 levels in CSF

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    End point title
    Change from Baseline of Amyloid Beta 1-40 levels in CSF
    End point description
    For Intention-to-treat (ITT) analysis set: Amyloid Beta levels 1-40 - change from baseline at week 76
    End point type
    Secondary
    End point timeframe
    Week 76
    End point values
    Treatment Placebo
    Number of subjects analysed
    10
    4
    Units: ng/L
        arithmetic mean (standard deviation)
    530.4 ± 885.5
    -418.8 ± 1049.7
    No statistical analyses for this end point

    Secondary: Change from Baseline of Amyloid Beta 1-42 levels in CSF

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    End point title
    Change from Baseline of Amyloid Beta 1-42 levels in CSF
    End point description
    For Intention-to-treat (ITT) analysis set: Amyloid Beta levels 1-42 - change from baseline at week 52
    End point type
    Secondary
    End point timeframe
    Baseline - Week 52
    End point values
    Treatment Placebo
    Number of subjects analysed
    6
    3
    Units: ng/L
        arithmetic mean (standard deviation)
    35.7 ± 33.2
    -12.3 ± 47.4
    No statistical analyses for this end point

    Secondary: Change from Baseline of Amyloid Beta 1-42 levels in CSF

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    End point title
    Change from Baseline of Amyloid Beta 1-42 levels in CSF
    End point description
    For Intention-to-treat (ITT) analysis set: Amyloid Beta levels 1-42 - change from baseline at week 76
    End point type
    Secondary
    End point timeframe
    Baseline - Week 76
    End point values
    Treatment Placebo
    Number of subjects analysed
    10
    4
    Units: ng/L
        arithmetic mean (standard deviation)
    35.9 ± 44.2
    -29.0 ± 71.9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    For the purpose of safety reporting, the study period for all AEs occuring was defined as the interval between the signature of the informed consent by the subject and the end of the follow-up period (or last visit/assessment in case of early termination)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23
    Reporting groups
    Reporting group title
    All subjects
    Reporting group description
    -

    Reporting group title
    Active
    Reporting group description
    -

    Reporting group title
    Placebo
    Reporting group description
    -

    Serious adverse events
    All subjects Active Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 21 (23.81%)
    3 / 14 (21.43%)
    2 / 7 (28.57%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischemic attack
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Foot deformity
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 infection
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    All subjects Active Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 21 (100.00%)
    14 / 14 (100.00%)
    7 / 7 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Phlebitis superficial
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Fatigue
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
         occurrences all number
    2
    1
    1
    Feeling abnormal
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Gait disturbance
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Hernia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Injection site pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Agitation
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Alcohol use disorder
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Depression
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Depressive symptom
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Post-traumatic amnestic disorder
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Sleep disorder
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Face injury
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Fall
         subjects affected / exposed
    3 / 21 (14.29%)
    2 / 14 (14.29%)
    1 / 7 (14.29%)
         occurrences all number
    7
    6
    1
    Hand fracture
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Head injury
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Joint dislocation
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Joint injury
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Procedural pain
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Mean cell volume increased
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Platelet count increased
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Atrioventricular block
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Cough
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Epistaxis
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    3
    3
    0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Cerebral microhaemorrhage
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Dementia Alzheimer's type
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Dizziness
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
         occurrences all number
    3
    1
    2
    Headache
         subjects affected / exposed
    4 / 21 (19.05%)
    2 / 14 (14.29%)
    2 / 7 (28.57%)
         occurrences all number
    4
    2
    2
    Hypoaesthesia
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    3
    3
    0
    Memory impairment
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Paraesthesia
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    4
    4
    0
    Presyncope
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Sciatica
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Eye disorders
    Eye pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Dry eye
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal discomfort
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    6
    6
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Colitis microscopic
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Diarrhoea
         subjects affected / exposed
    3 / 21 (14.29%)
    1 / 14 (7.14%)
    2 / 7 (28.57%)
         occurrences all number
    4
    2
    2
    Dyspepsia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    2
    0
    2
    Nausea
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Periodontal disease
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Vomiting
         subjects affected / exposed
    3 / 21 (14.29%)
    2 / 14 (14.29%)
    1 / 7 (14.29%)
         occurrences all number
    3
    2
    1
    Toothache
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Haematuria
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
         occurrences all number
    3
    2
    1
    Urinary incontinence
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Hepatobiliary disorders
    Gallbladder polyp
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    2
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Psoriasis
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Rash
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Skin lesion
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 21 (19.05%)
    4 / 14 (28.57%)
    0 / 7 (0.00%)
         occurrences all number
    4
    4
    0
    Back pain
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Groin pain
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Limb mass
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    2
    2
    0
    Muscle spasms
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 21 (14.29%)
    2 / 14 (14.29%)
    1 / 7 (14.29%)
         occurrences all number
    4
    3
    1
    Musculoskeletal pain
         subjects affected / exposed
    5 / 21 (23.81%)
    3 / 14 (21.43%)
    2 / 7 (28.57%)
         occurrences all number
    6
    4
    2
    Myalgia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    3
    3
    0
    Neck pain
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    3
    3
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Pain in extremity
         subjects affected / exposed
    3 / 21 (14.29%)
    3 / 14 (21.43%)
    0 / 7 (0.00%)
         occurrences all number
    11
    11
    0
    Pain in jaw
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Folate deficiency
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Conjunctivitis
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
         occurrences all number
    2
    1
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    4 / 21 (19.05%)
    3 / 14 (21.43%)
    1 / 7 (14.29%)
         occurrences all number
    4
    3
    1
    Oral herpes
         subjects affected / exposed
    3 / 21 (14.29%)
    3 / 14 (21.43%)
    0 / 7 (0.00%)
         occurrences all number
    5
    5
    0
    Pneumonia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
         occurrences all number
    4
    4
    0
    Sinusitis
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Tooth infection
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
         occurrences all number
    1
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 21 (19.05%)
    4 / 14 (28.57%)
    0 / 7 (0.00%)
         occurrences all number
    5
    5
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
         occurrences all number
    3
    1
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Jul 2018
    Version 2.0: Based on Swedish Medicinal Products Agency (MPA) questions. A more suitable observation time following dose administration was added. SUSARS will be communicated to all investigators taking part in this multi-center trial in addition to the Competent Authority and Ethics Committee. End of trial, clearly defined in the protocol as 'last patient last visit'. The investigator will be required to provide a written statement to confirm that he/she has carefully assessed that the patient is able to give written informed consent.
    23 Aug 2018
    Version 3.0: The change consists of stating the types of IUDs that would be considered acceptable for use in the ACI -24-1801 clinical trial in exclusion criteria
    24 Oct 2019
    Version 4.0: The decision on expansion to 45 patients will be based on the antibody responders from the interim analysis at 12 months, including target engagement data. Modification of the eligibility criteria following the request from the Polish MoH to outline the contraceptive measures for male patients. Update of the status of ACl-24-0701 phase I study as per latest available information. Change of the instructions for Drug administration to favor the injection into the deltoid muscle of the arm. Update of the temperature conditions for Drug preparation and administration. Update of drug inventory using drug destruction on site after Sponsor's approval. Update of the vital signs measures to be aligned with the eCRF design and data capture. Use of patient diary to report adverse events and medications taken between patient-visits. Clarification on restriction of use of certain prior/concomitant medications. Extension of the screening period taking into consideration sites' feedback on the difficulty to adhere to screening window.
    05 May 2020
    Version 5.0 On-site visit 14 (week 52) could not be performed in 6 patients. Instead, safety assessments of V14 are replaced by a telephone interview. Where possible, the assessments skipped at V14 including Lumbar Puncture, MRI and PET scan will be performed at a later date during an unscheduled visit. As a consequence, the second interim analysis planned in patients having reached 52 weeks will be conducted in less subjects than planned. In case the results at this time point are non-conclusive, the decision to expand cohort 1 to 45 patients may be deferred to the interim analysis of 18 months at week 76. Handling of potentially delayed visits 15 to 18 is described.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to pandemic COVID-19 limitations, some post-treatment subject visits at 1 year (week 52) were not performed. Therefore, some amyloid PET scans , lumbar punctures and blood sampling were not performed.
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