Two phase 2 multiple ascending-dose studies of vanutide cridificar (ACC-001) and QS-21 adjuvant in mild-to-moderate Alzheimer's disease

Journal of Alzheimer's Disease

Volumn 51, Issue 4, 2016, Pages 1131-1143

  Pasquier, Florence ^a,g   Sadowsky, Carl ^b   Holstein, Ann ^c   Leterme, Ghislaine Le Prince ^d   Peng, Yahong ^c   Jackson, Nicholas ^c   Fox, Nick C ^e   Ketter, Nzeera ^f   Liu, Enchi ^f   Ryan, J Michael ^c  

^a CHU Lille   (France)

^b Palm Beach Neurology   (United States)

^c Pfizer Vaccines   (United States)

^d PFIZER INC   (United States)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

^f JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^g LILLE UNIVERSITY HOSPITAL   (France)

Author keywords

Active immunization; Alzheimer's disease; amyloid plaques; amyloid peptides; amyloid protein; clinical trial; immunotherapy

Indexed keywords

IMMUNOGLOBULIN G1; PLACEBO; QS 21; VANUTIDE CRIDIFICAR; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); GAMMA INTERFERON; HYBRID PROTEIN; IMMUNOLOGICAL ADJUVANT; NEUROLEPTIC AGENT; PEPTIDE FRAGMENT; SAPONIN;

ADULT; AGED; ALZHEIMER DISEASE; ANTIBODY TITER; ARTICLE; BRAIN EDEMA; CEREBROSPINAL FLUID; COGNITION; COHORT ANALYSIS; CONTROLLED STUDY; DEPRESSION; DIARRHEA; DISEASE SEVERITY; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FOLLOW UP; HEADACHE; HEART ARREST; HEART INFARCTION; HUMAN; IMMUNOGENICITY; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; INJECTION SITE SWELLING; LUNG CANCER; MAJOR CLINICAL STUDY; MALE; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT RESPONSE; VACCINATION; VASCULITIS; VOLUMETRY; BLOOD; CLINICAL TRIAL; DIAGNOSTIC IMAGING; DOSE RESPONSE; MIDDLE AGED; MULTICENTER STUDY; NEUROPSYCHOLOGICAL TEST; SINGLE BLIND PROCEDURE; TREATMENT OUTCOME;

ADJUVANTS, IMMUNOLOGIC; AGED; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANTIPSYCHOTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FOLLOW-UP STUDIES; HUMANS; INTERFERON-GAMMA; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; PEPTIDE FRAGMENTS; RECOMBINANT FUSION PROTEINS; SAPONINS; SINGLE-BLIND METHOD; TREATMENT OUTCOME;

EID: 84964805128     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-150376     Document Type: Article

References (32)

1. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353 - 356.
2. Selkoe DJ (2011) Alzheimer's disease. Cold Spring Harb Perspect Biol 3, pii - a004457.
3. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; Dominantly Inherited Alzheimer Network (2012) Clinical and biomarker changes in dominantly inherited Alzheimer's disease [Erratum, N Engl J Med 2012; 780]. N Engl J Med 367, 795 - 804.
4. Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer's disease: An appraisal for the development of therapeutics. Nat Rev Drug Discov 10, 698 - 712.
5. Schenk D (2002) Amyloid-beta immunotherapy for Alzheimer's disease: The end of the beginning. Nat Rev Neurosci 3, 824 - 828.
6. Pride M, Seubert P, Grundman M, Hagen M, Eldridge J, Black RS (2008) Progress in the active immunotherapeutic approach to Alzheimer's disease: Clinical investigations into AN1792-associated meningoencephalitis. Neurodegener Dis 5, 194 - 196.
7. Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: A case report. Nat Med 9, 448 - 452.
8. Ferrer I, Boada Rovira M, Sánchez Guerra ML, Rey MJ, Costa-Jussá F (2004) Neuropathology and pathogenesis of encephalitis following amyloid-β immunization in Alzheimer's disease. Brain Pathol 14, 11 - 20.
9. Masliah E, Hansen L, Adame A, Crews L, Bard F, Lee C, Seubert P, Games D, Kirby L, Schenk D (2005) Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease.Neurology 64, 129 - 131.
10. Bombois S, Maurage CA, Gompel M, Deramecourt V, Mackowiak-Cordoliani MA, Black RS, Lavielle R, Delacourte A, Pasquier F (2007) Absence of beta-amyloid deposits after immunization in Alzheimer disease with Lewy body dementia. Arch Neurol 64, 583 - 587.
11. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA (2008) Long-term effects of Aβ42 immunisation in Alzheimer's disease: Follow-up of a randomised, placebo-controlled phase I trial. Lancet 372, 216 - 223.
12. Boche D, Denham N, Holmes C, Nicoll JAR (2010) Neuropathology after active Aβ42 immunotherapy: Implications for Alzheimer's disease pathogenesis. Acta Neuropathol 120, 369 - 384.
13. Serrano-Pozo A, William CM, Ferrer I, Uro-Coste E, Delisle MB, Maurage CA, Hock C, Nitsch RM, Masliah E, Growdon JH, Frosch MP, Hyman BT (2010) Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and tau pathology. Brain 133, 1312 - 1327.
14. Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM; AN1792(QS-21)-201 Study Team (2005) Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.Neurology 64, 1553 - 1562.
15. Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C (2003) Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization.Neurology 61, 46 - 54.
16. Cribbs DH, Ghochikyan A, Vasilevko V, Tran M, Petrushina I, Sadzikava N, Babikyan D, Kesslak P, Kieber-Emmons T, Cotman CW, Agadjanyan MG (2003) Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid. Int Immunol 15, 505 - 514.
17. Hagen M, Seubert P, Jacobsen S, Schenk D, Pride M, Arumugham R, Warner G, Kinney G (2011) The Aβ peptide conjugate vaccine, acc-001, generates n-terminal anti-Aβ antibodies in the absence of Aβ directed t-cell responses. Alzheimers Dement 7, S460 - S461.
18. Arai H, Suzuki H, Yoshiyama T, Lobello K, Peng Y, Liu E, Ketter N, Margolin R, Jackson N, Fujimoto Y (2013) Safety, tolerability and immunogenicity of an immunotherapeutic vaccine (vanutide cridificar [ACC-001]) and the QS-21 adjuvant in Japanese individuals with mild-to-moderate Alzheimer's disease: A phase IIa, multicenter, randomized, adjuvant and placebo clinical trial. Alzheimers Dement 9, 282.
19. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR; Bapineuzumab 301 and 302 Clinical Trial Investigators (2014) Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med 370, 322 - 333.
20. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease.Neurology 34, 939 - 944.
21. Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state." A practical method for grading the cognitive state of patients for the clinician.J Psychiatr Res 12, 189 - 198.
22. Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, Raman R, Sun X, Aisen PS, Siemers E, Liu-Seifert H, Mohs R; Alzheimer's Disease Cooperative Study Steering Committee, Solanezumab Study Group (2014) Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med 370, 311 - 321.
23. Rasmusson DX, Brandt J, Steele C, Hedreen JC, Troncoso JC, Folstein MF (1996) Accuracy of clinical diagnosis of Alzheimer disease and clinical features of patients with non-Alzheimer disease neuropathology. Alzheimer Dis Assoc Disord 10, 180 - 188.
24. Lim A, Tsuang D, Kukull W, Nochlin D, Leverenz J, McCormick W, Bowen J, Teri L, Thompson J, Peskind ER, Raskind M, Larson EB (1999) Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series.J Am Geriatr Soc 47, 564 - 569.
25. Farlow MR, Andreasen N, Riviere ME, Vostiar I, Vitaliti A, Sovago J, Caputo A, Winblad B, Graf A (2015) Long-term treatment with active Aβ immunotherapy with CAD106 in mild Alzheimer's disease. Alzheimers Res Ther 7, 23.
26. Fox NC, Black RS, Gilman S, Rossor MN, Griffith SG, Jenkins L, Koller M; AN1792(QS-21)-201 Study (2005) Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease.Neurology 64, 1563 - 1572.
27. Black RS, Sperling RA, Safirstein B, Motter RN, Pallay A, Nichols A, Grundman M (2010) A single ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis Assoc Disord 24, 198 - 203.
28. Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, Maguire RP, Blennow K, Lundmark J, Staufenbiel M, Orgogozo JM, Graf A (2012) Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: Randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol 11, 597 - 604.
29. Adolfsson O, Philgren M, Toni N, Varisco Y, Buccarello AL, Antoniello K, Lohmann S, Piorkowska K, Gafner V, Atwal JK, Maloney J, Chen M, Gogineni A, Weimer RM, Mortensen DL, Friesenhahn M, Ho C, Paul R, Pfeifer A, Muhs A, Watts RJ (2012) An effector-reduced anti-β-amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Aβ.J Neurosci 32, 9677 - 9689.
30. Bard F, Cannon C, Barbour R, Burke RL, Games D, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Lieberburg I, Motter R, Nguyen M, Soriano F, Vasquez N, Weiss K, Welch B, Seubert P, Schenk D, Yednock T (2000) Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6, 916 - 919.
31. Blennow K, Zetterberg H, Rinne JO, Salloway S, Wei J, Black R, Grundman M, Liu E; AAB-001 201/202 Investigators (2012) Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol 69, 1002 - 1010.
32. Karran E, Hardy J (2014) Antiamyloid therapy for Alzheimer's disease- are we on the right road?. N Engl J Med 370, 377 - 378.