Study Evaluating Safety, Tolerability, And Immunogenicity Of ACC-001 In Subjects With Mild To Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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To assess the safety, tolerability, and immunogenicity of ACC-001, an investigational active immunization, in patients with mild to moderate Alzheimer's disease.

Official Title
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A Phase Iia, Multicenter, Randomized, Third-party Unblinded, Adjuvant And Placebo-controlled, Multiple Ascending Dose, Safety, Tolerability And Immunogenicity Trial Of Acc-001 And Qs-21 Adjuvant In Subjects With Mild To Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: ACC-001 + QS-21
* Biological: ACC-001
* Biological: QS-21
* Drug: Placebo: Phosphate buffered saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of probable Alzheimer's Disease with Mini-Mental State Examination (MMSE) score of 16-26 (except Germany: 21-26) Brain MRI consistent with Alzheimer Disease Concurent use of Chloniesterase inhibitor or memantine allowed if stable Other inclusion criteria apply Exclusion Criteria: Significant Neurological Disease other than Alzheimer's disease Major psychiatric disorder Contraindication to undergo brain MRI Clinically significant systemic illness Other exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>arm 1: ACC-001 (Vanutide Cridificar)+ QS-21 | Biological: ACC-001 + QS-21<br>* Vanutide Cridificar (3, 10, 30µg) + QS-21 (50µg), IM on day 1, month 1, month 3, month 6 and month 12<br>|
| Active Comparator: 2<br>arm 2: ACC-001 | Biological: ACC-001<br>* Vanutide Cridificar (10, 30µg), IM on day 1, month 1, month 3, month 6 and month 12<br>|
| Placebo Comparator: 3<br>arm 3: QS-21 | Biological: QS-21<br>* QS-21 (50µg), IM on day 1, month 1, month 3, month 6 and month 12<br>|
| Placebo Comparator: 4<br>Drug: Phosphate Buffered Saline (PBS) | Drug: Placebo: Phosphate buffered saline<br>* Phosphate buffered Saline (pH : 7.4), IM on day 1, month 1, month 3, month 6 and month 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-emergent AEs or Serious Adverse Events (SAEs) | An AE was any untoward, undesired, or unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study drug or in a sponsor's clinical study. The event did not need to be causally related to the study drug or the clinical studies. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | approximately 110 weeks, including a 6-week screening period, 52 weeks of dosing and 54 weeks for follow-up after the last dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Anti-A-beta Immunoglobulin G (IgG) Total Using an Enzyme-linked Immunosorbent Assay (ELISA) at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 | The lower limit of quantification (LLOQ) was 100 U/mL and when the assay result was below LLOQ (100 U/mL), 50 U/mL was imputed for IgG. | Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 | 
| GMTs of Anti-A-beta Immunoglobulin M (IgM) Using ELISA at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 | The LLOQ was 50 U/mL and when the assay result was below LLOQ (50 U/mL), 25 U/mL was imputed for IgM. | Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 | 
| Change From Baseline GMTs of Anti-A-beta IgG Subtypes Using ELISA at Visits Where an IgG Total Response is Measurable (at Weeks 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 if Applicable) | IgG subtypes were not assessed | Baseline, Week 2, 4, 6, 8, 10, 14, 16, 24, 28, 30, 40, 50, 54, 56, 66, 78, 91, and 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, active immunization