Safety, Tolerability and Abeta-specific Antibody Response of Repeated i.m. Injections of Adjuvanted CAD106 in Mild Alzheimer Patients

Study Overview
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Brief Summary
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This study will assess the safety, tolerability and Abeta-specific antibody response of repeated intra-muscular injections of adjuvanted CAD106 in patients with mild Alzheimer's Disease.

Official Title
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A 90-week, Multi-center, Randomized, Double-blind, Placebo-controlled Study in Patients With Mild Alzheimer's Disease (AD) to Investigate the Safety, Tolerability and Abeta-specific Antibody Response Following Repeated i.m. Injections of Adjuvanted CAD106

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Biological: CAD106
* Biological: Placebo
* Biological: Alum
* Biological: MF59


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and/or female patients below 85 years of age (inclusive) Diagnosis of mild Alzheimer's Disease Mini-Mental State Examination (MMSE) 20 to 26 (inclusive) at screening, untreated or on stable dose of cholinesterase inhibitor or memantine over the last 4 weeks prior to clinical assessments Exclusion Criteria: Previously participated in an AD vaccine study and received active treatment History or presence of an active autoimmune disease History or presence of seizure disorder Presence of significant coronary heart disease and/or cerebrovascular disease Presence of other neurodegenerative disease and/or psychiatric disorders (with the exception of successfully treated depression) Advanced, severe, progressive or unstable disease that might interfere with the safety, tolerability and pharmacodynamic assessments of the patient Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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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: CAD106 150μg + Adjuvant 1 at middle dose<br> | Biological: CAD106<br>* 150μg and 450μg doses were reconstituted and administered via intramuscular injection<br>Biological: MF59<br>* An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106<br>|
| Active Comparator: CAD106 150μg + Adjuvant 1 at low dose<br> | Biological: CAD106<br>* 150μg and 450μg doses were reconstituted and administered via intramuscular injection<br>Biological: MF59<br>* An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106<br>|
| Placebo Comparator: Placebo + Adjuvant 1 at middle dose<br> | Biological: Placebo<br>* Identical placebo to CAD106 administered via intramuscular injection<br>|
| Active Comparator: CAD106 150μg + Adjuvant 2 at middle dose<br> | Biological: CAD106<br>* 150μg and 450μg doses were reconstituted and administered via intramuscular injection<br>Biological: MF59<br>* An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106<br>|
| Active Comparator: CAD106 150μg + Adjuvant 2 at low dose<br> | Biological: CAD106<br>* 150μg and 450μg doses were reconstituted and administered via intramuscular injection<br>Biological: MF59<br>* An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106<br>|
| Placebo Comparator: Placebo + Adjuvant 2 at middle dose<br> | Biological: Placebo<br>* Identical placebo to CAD106 administered via intramuscular injection<br>|
| Active Comparator: CAD106 450μg + either Adjuvant 1 or 2 at middle dose<br> | Biological: CAD106<br>* 150μg and 450μg doses were reconstituted and administered via intramuscular injection<br>Biological: Alum<br>* An adjuvant (additive to increase potency ) of low, middle or high doses which was mixed with reconstituted active CAD106<br>Biological: MF59<br>* An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106<br>|
| Active Comparator: CAD106 450μg + either Adjuvant 1 or 2 at low dose<br> | Biological: CAD106<br>* 150μg and 450μg doses were reconstituted and administered via intramuscular injection<br>Biological: Alum<br>* An adjuvant (additive to increase potency ) of low, middle or high doses which was mixed with reconstituted active CAD106<br>Biological: MF59<br>* An adjuvant (additive to increase potency) of low, middle and high doses which was mixed with reconstituted active CAD106<br>|
| Placebo Comparator: Placebo + either Adjuvant 1 or 2 at middle dose<br> | Biological: Placebo<br>* Identical placebo to CAD106 administered via intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability assessments (physical/neurological examinations, electrocardiogram (ECG), vital signs, standard and special laboratory evaluations, Magnetic Resonance Imaging (MRIs), Adverse events / Serious adverse events (AE/SAE) monitoring). |  | Screening and through the end of the study to Week 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amyloid beta (Aβ)-specific and Qβ carrier-specific antibody response to CAD106 (with either adjuvant) in serum and cerebrospinal fluid (CSF) |  | Screening and through the end of the study to Week 90 | 
| Amyloid beta (Aβ)-specific and Qβ carrier-specific T-cell response to CAD106 (with either adjuvant) using peripheral blood mononuclear cells (PBMCs) |  | Screening and at week 8 | 
| Changes over time of the concentrations of disease related markers (Aβ1-40 and Aβ1-42 in plasma; Aβ1-40, Aβ1-42, total-tau, phospho-tau in CSF, or other markers) in patients with mild AD receiving CAD106 (with either adjuvant) compared to placebo |  | Screening and through the end of the study to Week 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Active immunization, Alzheimer disease, Antibody, Central Nervous System Diseases, Neurodegenerative diseases