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 journalArticle

25 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 languageEnglish (US)
Pages (from-to)10-22
Number of pages13
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2017

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Active Immunotherapy
Amyloid
Alzheimer Disease
Positron-Emission Tomography
Placebos
Confidence Intervals
Intramuscular Injections
Area Under Curve
Antibody Formation
Central Nervous System
Research Personnel
Inflammation
Safety
Serum
Pharmaceutical Preparations

Keywords

  • Active immunotherapy
  • Alzheimer's disease
  • Amyloid-beta peptides
  • Biological biomarkers
  • CAD106
  • Safety

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Active Aβ immunotherapy CAD106 in Alzheimer's disease : A phase 2b study. / Vandenberghe, Rik; Riviere, Marie Emmanuelle; Caputo, Angelika; Sovago, Judit; Maguire, R. Paul; Farlow, Martin; Marotta, Giovanni; Sanchez-Valle, Raquel; Scheltens, Philip; Ryan, J. Michael; Graf, Ana.

In: Alzheimer's and Dementia: Translational Research and Clinical Interventions, Vol. 3, No. 1, 01.01.2017, p. 10-22.

Research output: Contribution to journalArticle

Vandenberghe, R, Riviere, ME, Caputo, A, Sovago, J, Maguire, RP, Farlow, M, Marotta, G, Sanchez-Valle, R, Scheltens, P, Ryan, JM & Graf, A 2017, 'Active Aβ immunotherapy CAD106 in Alzheimer's disease: A phase 2b study', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 3, no. 1, pp. 10-22. https://doi.org/10.1016/j.trci.2016.12.003
Vandenberghe, Rik ; Riviere, Marie Emmanuelle ; Caputo, Angelika ; Sovago, Judit ; Maguire, R. Paul ; Farlow, Martin ; Marotta, Giovanni ; Sanchez-Valle, Raquel ; Scheltens, Philip ; Ryan, J. Michael ; Graf, Ana. / Active Aβ immunotherapy CAD106 in Alzheimer's disease : A phase 2b study. In: Alzheimer's and Dementia: Translational Research and Clinical Interventions. 2017 ; Vol. 3, No. 1. pp. 10-22.
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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.",
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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

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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.

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