Active Aβ immunotherapy CAD106 in Alzheimer's disease: A phase 2b study

Rik Vandenberghe; Marie-Emmanuelle Riviere; Angelika Caputo; Judit Sovago; R Paul Maguire; Martin Farlow; Giovanni Marotta; Raquel Sanchez-Valle; Philip Scheltens; J Michael Ryan; Ana Graf

doi:https://doi.org/10.1016/j.trci.2016.12.003

Active Aβ immunotherapy CAD106 in Alzheimer's disease: A phase 2b study

Rik Vandenberghe, Marie-Emmanuelle Riviere, Angelika Caputo, Judit Sovago, R Paul Maguire, Martin Farlow, Giovanni Marotta, Raquel Sanchez-Valle, Philip Scheltens, J Michael Ryan, Ana Graf

Research output: Contribution to journal › Article › Academic › peer-review

104 Citations (Scopus)

Abstract

INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant in patients with mild Alzheimer's disease.

METHODS: One hundred twenty-one patients received up to seven intramuscular injections of CAD106 (150 μg or 450 μg) or placebo ± adjuvant over 60 weeks. An amyloid positron emission tomography (PET) substudy was also conducted.

RESULTS: CAD106 induced strong serological responses (amyloid-beta [Aβ]-Immunoglobuline G[IgG]) in 55.1% (150 μg) and 81.1% (450 μg) of patients (strong serological responders [SSRs]). Serious adverse events (SAEs) were reported in 24.5% (95% confidence interval [CI] 16.7-33.8) of the patients in the active treatment group and in 6.7% (95% CI 0.2-31.9) in the placebo group. Three of the SAEs were classified as possibly related to study drug by the investigators. No evidence of central nervous system inflammation was found. Amyloid-related imaging abnormalities (ARIAs) occurred in six cases, all of them were strong serological responders. None of the ARIAs were symptomatic. Serum Aβ-IgG titer area under the curves correlated negatively with amyloid PET standardized uptake value ratio percentage change from baseline to week 78 within the CAD106-treated patients (r = -0.84, P = .0004). Decrease in cortical gray-matter volume from baseline to week 78 was larger in SSRs than in controls (P = .0077).

DISCUSSION: Repeated CAD106 administration was generally well tolerated. CAD106 450 μg with alum adjuvant demonstrated the best balance between antibody response and tolerability.

Original language	English
Pages (from-to)	10-22
Number of pages	13
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.trci.2016.12.003
Publication status	Published - Jan 2017

Access to Document

https://doi.org/10.1016/j.trci.2016.12.003

Cite this

Vandenberghe, R., Riviere, M.-E., Caputo, A., Sovago, J., Maguire, R. P., Farlow, M., Marotta, G., Sanchez-Valle, R., Scheltens, P., Ryan, J. M., & Graf, A. (2017). Active Aβ immunotherapy CAD106 in Alzheimer's disease: A phase 2b study. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 3(1), 10-22. https://doi.org/10.1016/j.trci.2016.12.003

@article{90c62524d3fd48efa49f3cf32c9108ce,

title = "Active Aβ immunotherapy CAD106 in Alzheimer's disease: A phase 2b study",

abstract = "INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant in patients with mild Alzheimer's disease.METHODS: One hundred twenty-one patients received up to seven intramuscular injections of CAD106 (150 μg or 450 μg) or placebo ± adjuvant over 60 weeks. An amyloid positron emission tomography (PET) substudy was also conducted.RESULTS: CAD106 induced strong serological responses (amyloid-beta [Aβ]-Immunoglobuline G[IgG]) in 55.1% (150 μg) and 81.1% (450 μg) of patients (strong serological responders [SSRs]). Serious adverse events (SAEs) were reported in 24.5% (95% confidence interval [CI] 16.7-33.8) of the patients in the active treatment group and in 6.7% (95% CI 0.2-31.9) in the placebo group. Three of the SAEs were classified as possibly related to study drug by the investigators. No evidence of central nervous system inflammation was found. Amyloid-related imaging abnormalities (ARIAs) occurred in six cases, all of them were strong serological responders. None of the ARIAs were symptomatic. Serum Aβ-IgG titer area under the curves correlated negatively with amyloid PET standardized uptake value ratio percentage change from baseline to week 78 within the CAD106-treated patients (r = -0.84, P = .0004). Decrease in cortical gray-matter volume from baseline to week 78 was larger in SSRs than in controls (P = .0077).DISCUSSION: Repeated CAD106 administration was generally well tolerated. CAD106 450 μg with alum adjuvant demonstrated the best balance between antibody response and tolerability.",

author = "Rik Vandenberghe and Marie-Emmanuelle Riviere and Angelika Caputo and Judit Sovago and Maguire, {R Paul} and Martin Farlow and Giovanni Marotta and Raquel Sanchez-Valle and Philip Scheltens and Ryan, {J Michael} and Ana Graf",

year = "2017",

month = jan,

doi = "https://doi.org/10.1016/j.trci.2016.12.003",

language = "English",

volume = "3",

pages = "10--22",

journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",

issn = "2352-8737",

publisher = "Elsevier Inc.",

number = "1",

}

TY - JOUR

T1 - Active Aβ immunotherapy CAD106 in Alzheimer's disease

T2 - A phase 2b study

AU - Vandenberghe, Rik

AU - Riviere, Marie-Emmanuelle

AU - Caputo, Angelika

AU - Sovago, Judit

AU - Maguire, R Paul

AU - Farlow, Martin

AU - Marotta, Giovanni

AU - Sanchez-Valle, Raquel

AU - Scheltens, Philip

AU - Ryan, J Michael

AU - Graf, Ana

PY - 2017/1

Y1 - 2017/1

N2 - INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant in patients with mild Alzheimer's disease.METHODS: One hundred twenty-one patients received up to seven intramuscular injections of CAD106 (150 μg or 450 μg) or placebo ± adjuvant over 60 weeks. An amyloid positron emission tomography (PET) substudy was also conducted.RESULTS: CAD106 induced strong serological responses (amyloid-beta [Aβ]-Immunoglobuline G[IgG]) in 55.1% (150 μg) and 81.1% (450 μg) of patients (strong serological responders [SSRs]). Serious adverse events (SAEs) were reported in 24.5% (95% confidence interval [CI] 16.7-33.8) of the patients in the active treatment group and in 6.7% (95% CI 0.2-31.9) in the placebo group. Three of the SAEs were classified as possibly related to study drug by the investigators. No evidence of central nervous system inflammation was found. Amyloid-related imaging abnormalities (ARIAs) occurred in six cases, all of them were strong serological responders. None of the ARIAs were symptomatic. Serum Aβ-IgG titer area under the curves correlated negatively with amyloid PET standardized uptake value ratio percentage change from baseline to week 78 within the CAD106-treated patients (r = -0.84, P = .0004). Decrease in cortical gray-matter volume from baseline to week 78 was larger in SSRs than in controls (P = .0077).DISCUSSION: Repeated CAD106 administration was generally well tolerated. CAD106 450 μg with alum adjuvant demonstrated the best balance between antibody response and tolerability.

AB - INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant in patients with mild Alzheimer's disease.METHODS: One hundred twenty-one patients received up to seven intramuscular injections of CAD106 (150 μg or 450 μg) or placebo ± adjuvant over 60 weeks. An amyloid positron emission tomography (PET) substudy was also conducted.RESULTS: CAD106 induced strong serological responses (amyloid-beta [Aβ]-Immunoglobuline G[IgG]) in 55.1% (150 μg) and 81.1% (450 μg) of patients (strong serological responders [SSRs]). Serious adverse events (SAEs) were reported in 24.5% (95% confidence interval [CI] 16.7-33.8) of the patients in the active treatment group and in 6.7% (95% CI 0.2-31.9) in the placebo group. Three of the SAEs were classified as possibly related to study drug by the investigators. No evidence of central nervous system inflammation was found. Amyloid-related imaging abnormalities (ARIAs) occurred in six cases, all of them were strong serological responders. None of the ARIAs were symptomatic. Serum Aβ-IgG titer area under the curves correlated negatively with amyloid PET standardized uptake value ratio percentage change from baseline to week 78 within the CAD106-treated patients (r = -0.84, P = .0004). Decrease in cortical gray-matter volume from baseline to week 78 was larger in SSRs than in controls (P = .0077).DISCUSSION: Repeated CAD106 administration was generally well tolerated. CAD106 450 μg with alum adjuvant demonstrated the best balance between antibody response and tolerability.

U2 - https://doi.org/10.1016/j.trci.2016.12.003

DO - https://doi.org/10.1016/j.trci.2016.12.003

M3 - Article

C2 - 29067316

SN - 2352-8737

VL - 3

SP - 10

EP - 22

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions

IS - 1

ER -