Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer's disease (BLAZE)

Alzheimer's Research and Therapy

Volumn 10, Issue 1, 2018, Pages

  Salloway, Stephen ^a   Honigberg, Lee A ^b   Cho, William ^b   Ward, Michael ^b   Friesenhahn, Michel ^b   Brunstein, Flavia ^b   Quartino, Angelica ^b   Clayton, David ^b   Mortensen, Deborah ^b   Bittner, Tobias ^c   Ho, Carole ^b   Rabe, Christina ^b   Schauer, Stephen P ^b   Wildsmith, Kristin R ^b   Fuji, Reina N ^b   Suliman, Shehnaaz ^b   Reiman, Eric M ^d   Chen, Kewei ^d   Paul, Robert ^b  

^a BROWN UNIVERSITY   (United States)

^b GENENTECH INC   (United States)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

^d BANNER ALZHEIMER S INSTITUTE   (United States)

Author keywords

Alzheimer's disease; Antibodies; Biomarkers; Humanized; Monoclonal antibodies; Positron emission tomography

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; CRENEZUMAB; FLORBETAPIR F 18; FLUORODEOXYGLUCOSE; PLACEBO; AMYLOID BETA PROTEIN; BIOLOGICAL MARKER; MONOCLONAL ANTIBODY;

AGED; ALZHEIMER DISEASE; ANXIETY DISORDER; ARTICLE; BACKACHE; CLINICAL DEMENTIA RATING; COHORT ANALYSIS; CONTROLLED STUDY; DEPRESSION; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG MEGADOSE; FEMALE; HUMAN; INTENTION TO TREAT ANALYSIS; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MINI MENTAL STATE EXAMINATION; NEUROIMAGING; PHASE 2 CLINICAL TRIAL; PNEUMONIA; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN CEREBROSPINAL FLUID LEVEL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; STANDARDIZED UPTAKE VALUE RATIO; SUBCORTEX; UPPER RESPIRATORY TRACT INFECTION; WHITE MATTER; BLOOD; BRAIN; CEREBROSPINAL FLUID; CLINICAL TRIAL; DIAGNOSTIC IMAGING; IMMUNOLOGY; MULTICENTER STUDY; NUCLEAR MAGNETIC RESONANCE IMAGING; TREATMENT OUTCOME;

AGED; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; BIOMARKERS; BRAIN; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; POSITRON-EMISSION TOMOGRAPHY; TREATMENT OUTCOME;

EID: 85053737526     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/s13195-018-0424-5     Document Type: Article

References (35)

1. Karran E, Mercken M, De Strooper B. The amyloid cascade hypothesis for Alzheimer's disease: An appraisal for the development of therapeutics. Nat Rev Drug Discov. 2011;10:698-712.
2. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science. 2002;297:353-6.
3. Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron. 1991;6:487-98.
4. Adolfsson O, Pihlgren M, Toni N, Varisco Y, Buccarello AL, Antoniello K, et al. An effector-reduced anti-β-amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J Neurosci. 2012;32:9677-89.
5. Ultsch M, Li B, Maurer T, Mathieu M, Adolfsson O, Muhs A, et al. Structure of crenezumab complex with Aβ shows loss of β-hairpin. Sci Rep. 2016;6:39374.
6. Chen K, Roontiva A, Thiyyagura P, Lee W, Liu X, Ayutyanont N, et al. Improved power for characterizing longitudinal amyloid-β PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region. J Nucl Med. 2015;56:560-6.
7. Brendel M, Högenauer M, Delker A, Sauerbeck J, Bartenstein P, Seibyl J, et al. Improved longitudinal [(18)F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction. NeuroImage. 2015;108:450-9.
8. Landau SM, Fero A, Baker SL, Koeppe R, Mintun M, Chen K, et al. Measurement of longitudinal β-amyloid change with 18F-florbetapir PET and standardized uptake value ratios. J Nucl Med. 2015;56:567-74.
9. Cummings JL, Cohen S, Van Dyck C, Brody M, Curtis C, Cho W, et al. ABBY: A phase 2 randomized trial of crenezumab in mild-to-moderate Alzheimer's disease. Neurology. 2018;90:e1889-97.
10. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-98.
11. O'Bryant SE, Waring SC, Cullum CM, Hall J, Lacritz L, Massman PJ, et al. Staging dementia using clinical dementia rating scale sum of boxes scores: A Texas Alzheimer's research consortium study. Arch Neurol. 2008;65:1091-5.
12. Berg L, Miller JP, Baty J, Rubin EH, Morris JC, Figiel G. Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention. Ann Neurol. 1992;31:242-9.
13. Sano M, Raman R, Emond J, Thomas RG, Petersen R, Schneider LS, et al. Adding delayed recall to the Alzheimer disease assessment scale is useful in studies of mild cognitive impairment but not Alzheimer disease. Alzheimer Dis Assoc Disord. 2011;25:122-7.
14. Bittner T, Zetterberg H, Teunissen CE, Ostlund RE Jr, Militello M, Andreasson U, et al. Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of β-amyloid (1-42) in human cerebrospinal fluid. Alzheimers Dement. 2016;12:517-26.
15. Fonov V, Evans AC, Botteron K, Almli CR, McKinstry RC, Collins DL, et al. Unbiased average age-appropriate atlases for pediatric studies. NeuroImage. 2011;54:313-27.
16. Coupe P, Fonov V, Eskildsen S, Manjón J, Arnold D, Collins L. Influence of the training library composition on a patch-based label fusion method: Application to hippocampus segmentation on the ADNI dataset. Alzheimers Dement. 2011;7:S24.
17. Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Federico A, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17:479-89.
18. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208-19.
19. Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9:363-72.
20. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370:322-33.
21. Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69:198-207.
22. Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature. 2016;537:50-6.
23. Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H, et al. Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. 2016;12:110-20.
24. Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimers Res Ther. 2017;9:95.
25. Shokouhi S, Mckay JW, Baker SL, Kang H, Brill AB, Gwirtsman HE, et al. Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment. Alzheimers Res Ther. 2016;8:2.
26. Fleisher AS, Joshi AD, Sundell KL, Chen YF, Kollack-Walker S, Lu M, et al. Use of white matter reference regions for detection of change in florbetapir positron emission tomography from completed phase 3 solanezumab trials. Alzheimers Dement. 2017;13:1117-24.
27. Chiao P, Bedell BJ, Avants B, Zijdenbos AP, Grand'Maison M, O-Neill P, et al. Impact of reference/target region selection on amyloid PET standard uptake value ratios in the phase 1b PRIME study of aducanumab. J Nucl Med. [Epub ahead of print].
28. Uenaka K, Nakano M, Willis BA, Friedrich S, Ferguson-Sells L, Dean RA, et al. Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the amyloid β monoclonal antibody solanezumab in Japanese and white patients with mild to moderate Alzheimer disease. Clin Neuropharmacol. 2012;35:25-9.
29. Ritter A, Cummings J. Fluid biomarkers in clinical trials of Alzheimer's disease therapeutics. Front Neurol. 2015;6:186.
30. Cummings JL. Biomarkers in Alzheimer's disease drug development. Alzheimers Dement. 2011;7:e13-44.
31. Retout S, Gieschke R, Weber C, Charoin J, Volz D, Lasser R, et al. The importance of understanding the variable rate of progression among Alzheimer's disease patients: Data from the gantenerumab program. J Prev Alzheimers Dis. 2015;2:LB13.
32. Klein G, Delmar P, Hofmann C, Abi-Saab D, Andjelkovic M, Ristic S, et al. 24-month amyloid PET results of the gantenerumab high-dose open label extension studies. Alzheimer's Association International Conference July 22-26; Chicago; O1-09-03. 2018.
33. Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, et al. Treatment of early AD subjects with BAN2401, an anti-Aβ protofibril monoclonal antibody, significantly clears amyloid plaque and reduces clinical decline. Alzheimer's Association International Conference July 22-26; Chicago; DT-01-07. 2018.
34. Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, et al. Trial of Solanezumab for mild dementia due to Alzheimer's disease. N Engl J Med. 2018;378:321-30.
35. Blennow K, Zetterberg H, Rinne JO, Salloway S, Wei J, Black R, et al. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol. 2012;69:1002-10.