Trial of Solanezumab in Preclinical Alzheimer's Disease.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
21 Sep 2023
21 Sep 2023
Historique:
pmc-release:
21
03
2024
medline:
22
9
2023
pubmed:
17
7
2023
entrez:
17
7
2023
Statut:
ppublish
Résumé
Trials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results. We tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini-Mental State Examination of 25 or more (range, 0 to 30, with lower scores indicating poorer cognition), and elevated brain amyloid levels on A total of 1169 persons underwent randomization: 578 were assigned to the solanezumab group and 591 to the placebo group. The mean age of the participants was 72 years, approximately 60% were women, and 75% had a family history of dementia. At 240 weeks, the mean change in PACC score was -1.43 in the solanezumab group and -1.13 in the placebo group (difference, -0.30; 95% confidence interval, -0.82 to 0.22; P = 0.26). Amyloid levels on brain PET increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group. Amyloid-related imaging abnormalities (ARIA) with edema occurred in less than 1% of the participants in each group. ARIA with microhemorrhage or hemosiderosis occurred in 29.2% of the participants in the solanezumab group and 32.8% of those in the placebo group. Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease. (Funded by the National Institute on Aging and others; A4 ClinicalTrials.gov number, NCT02008357.).
Sections du résumé
BACKGROUND
BACKGROUND
Trials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results.
METHODS
METHODS
We tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini-Mental State Examination of 25 or more (range, 0 to 30, with lower scores indicating poorer cognition), and elevated brain amyloid levels on
RESULTS
RESULTS
A total of 1169 persons underwent randomization: 578 were assigned to the solanezumab group and 591 to the placebo group. The mean age of the participants was 72 years, approximately 60% were women, and 75% had a family history of dementia. At 240 weeks, the mean change in PACC score was -1.43 in the solanezumab group and -1.13 in the placebo group (difference, -0.30; 95% confidence interval, -0.82 to 0.22; P = 0.26). Amyloid levels on brain PET increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group. Amyloid-related imaging abnormalities (ARIA) with edema occurred in less than 1% of the participants in each group. ARIA with microhemorrhage or hemosiderosis occurred in 29.2% of the participants in the solanezumab group and 32.8% of those in the placebo group.
CONCLUSIONS
CONCLUSIONS
Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease. (Funded by the National Institute on Aging and others; A4 ClinicalTrials.gov number, NCT02008357.).
Identifiants
pubmed: 37458272
doi: 10.1056/NEJMoa2305032
pmc: PMC10559996
mid: NIHMS1933000
doi:
Substances chimiques
Amyloid beta-Peptides
0
Antibodies, Monoclonal, Humanized
0
solanezumab
5D6PWO0333
Banques de données
ClinicalTrials.gov
['NCT02008357']
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1096-1107Subventions
Organisme : NIA NIH HHS
ID : R01AG063689
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG063689
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG057437
Pays : United States
Organisme : NIA NIH HHS
ID : U19AG010483
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG010483
Pays : United States
Organisme : NIA NIH HHS
ID : U24AG057437
Pays : United States
Investigateurs
Reisa Sperling
(R)
Paul Aisen
(P)
Roy Yaari
(R)
Cheryl A Brown
(CA)
John R Sims
(JR)
Michael Donohue
(M)
Mike Rafii
(M)
Rema Raman
(R)
Robert Rissman
(R)
Cecily Jenkins
(C)
Gustavo Jimenez-Maggiora
(G)
Jeremy Pizzola
(J)
Alison Belsha
(A)
Clifford R Jack
(CR)
Jason Karlawish
(J)
Joshua Grill
(J)
James B Brewer
(JB)
Mark Mintun
(M)
Karen Holdridge
(K)
Isabella Velona
(I)
Kenneth Marek
(K)
John Seibyl
(J)
Marybeth Howlett
(M)
Paul Maruff
(P)
Keith Johnson
(K)
Aaron Schultz
(A)
Dorene Rentz
(D)
Kate Papp
(K)
Beth Mormino
(B)
Rebecca Amariglio
(R)
Gad Marshall
(G)
Dylan Kirn
(D)
Michael Properzi
(M)
J Alex Becker
(JA)
Rachel Buckley
(R)
Maria Arampatzidou
(M)
Jennifer Salazar
(J)
Paula Cohen
(P)
Jorge Gutierrez
(J)
Harriett Davey
(H)
Melissa Ruiz
(M)
Isabel Francis
(I)
Michael Rafii
(M)
Gabriela Muranevici
(G)
Tiffany Chow
(T)
Steve Bruno
(S)
Gina Garcia-Camilo
(G)
Adriana Bohorquez
(A)
Vedeline Torreon
(V)
Marianne Manire
(M)
Renarda Jones
(R)
Alyssa Carroll
(A)
Sarah Danowski
(S)
Deborah Tobias
(D)
Lindsey Earp
(L)
Dan Abinsay
(D)
Sarah Walter
(S)
Ryoko Ihara
(R)
Xavier Salazar
(X)
Stefanie Juliano
(S)
Sarah Espinoza
(S)
Shelley Moore
(S)
Taylor Clanton
(T)
Agnes Lewandowski
(A)
Phuoc Hong
(P)
Hongmei Qiu
(H)
Jia-Shing So
(JS)
Stefania Bruschi
(S)
Kimberlee Eudy
(K)
Quin Revel
(Q)
Michael Selsnik
(M)
Olusegun Adegoke
(O)
Veasna Tan
(V)
Olga Baryshnikava
(O)
Iris Sim Dacio
(IS)
Sandhya Niranjan Jaiswal
(SN)
Elizabeth Shaffer
(E)
Michelle Pablo
(M)
Karin Ernstrom
(K)
Gopalan Sethuraman
(G)
Jiyoon Choi
(J)
Oliver Langford
(O)
Shunran Wang
(S)
Andy Liu
(A)
Barbara Bartocci
(B)
Melissa Korba
(M)
Sara Abdel-Latif
(S)
Howard Feldman
(H)
Genny Matthews
(G)
Stephanie Parks
(S)
Jen Mason
(J)
Jason Young
(J)
Ashlee Heldreth
(A)
Janet Kastelan
(J)
Rebecca Ryan-Jones
(R)
Lindsay Cotton
(L)
Maria Bulger Lennox
(M)
Ronelyn Chavez
(R)
Tilman Oltersdorf
(T)
Curtis Taylor
(C)
Barbara LaPlante
(B)
Meghan Stirn
(M)
Joanne Brechlin
(J)
Gina Varner
(G)
Carol Evans
(C)
Karim Hussein
(K)
Erika Wilson
(E)
Ronald Thomas
(R)
Shelia Jin
(S)
James Barlow
(J)
Nichol Ferng
(N)
Robin Jennings
(R)
Leonardino Digma
(L)
Heidi Jacobs
(H)
Jorge Sepulcre
(J)
Justin Sanchez
(J)
Matthew Scott
(M)
Bret J Borowski
(BJ)
Petrice M Cogswell
(PM)
Cory A Johnson
(CA)
Kejal Kantarci
(K)
Leonard C Matoush
(LC)
William C Turke
(WC)
Ashritha L Reddy
(AL)
Denise A Reyes
(DA)
Kaely B Thostenson
(KB)
Samantha M Zuk
(SM)
Jeffrey M Burns
(JM)
Joshua D Grill
(JD)
David Sultzer
(D)
Reneé Tschopp
(R)
Donna Miles
(D)
Amy Fredrickson
(A)
François Windels
(F)
Bodil Hook
(B)
Lenny Nuciforo
(L)
Natalia Contreras
(N)
Patrick McCabe
(P)
Becky Watt Knight
(B)
Rachel Griffith
(R)
Melissa McGue
(M)
Shannon Conti
(S)
Amy Martin Vogt
(AM)
Andrea Abram
(A)
Bhavna Madduri
(B)
Cheryl A Brown
(CA)
Dillon Hilderbrand
(D)
John Brad Holmes
(JB)
John R Sims
(JR)
Julie Chandler
(J)
Keith Parsons
(K)
Lisa Ferguson-Sells
(L)
Marybeth Devine
(M)
Michael Case
(M)
Michele Mancini
(M)
Michael Pontecorvo
(M)
Peter Fairfield
(P)
Phyllis Ferrell
(P)
Satina Hall
(S)
Scott Kaiser
(S)
Sergey Shcherbinin
(S)
Stacy Huckins
(S)
Susan Warner
(S)
Jude Burger
(J)
Colin L Masters
(CL)
Andrew Huynh
(A)
Paul Yates
(P)
Georgios Zisis
(G)
Laura Marginson
(L)
Sarah Best
(S)
Rebecca Shostak
(R)
Kayla VanderPloeg
(K)
Elsa Mann
(E)
Julia Truemner
(J)
Sandra Black
(S)
Benjamin Lam
(B)
Chinthaka Heyn
(C)
Samantha Paul-Stotz
(S)
Maryna Butenko
(M)
Sharon Cohen
(S)
C Ian Cohen
(CI)
Atif Shaikh
(A)
Ellen Buchman
(E)
Barathy Tharmalingam
(B)
Linda Schlesinger
(L)
Robin Hsiung
(R)
Ellen Kim
(E)
Tahlee Marian
(T)
Haakon Nygaard
(H)
Benita Mudge
(B)
Michele Assaly
(M)
Takeshi Iwatsubo
(T)
Atsushi Iwata
(A)
Kazushi Suzuki
(K)
Yoshiki Niimi
(Y)
Ken-Ichiro Sato
(KI)
William J Burke
(WJ)
Roma Patel
(R)
Daniel Viramontes Apodaca
(D)
Sachin Y Pandya
(SY)
Anna D Burke
(AD)
Edward Zamrini
(E)
Zoran Obradov
(Z)
Christine M Belden
(CM)
Carol Cline
(C)
Margaret Rich
(M)
Lisa Roye
(L)
Marwan Sabbagh
(M)
Sydney O'Connor
(S)
Valory Pavlik
(V)
Melissa Yu
(M)
Shayla Yonce
(S)
Angela Okolie
(A)
Uzma Khan
(U)
Esteban Olivera
(E)
Elma Fallejo
(E)
Jennifer West
(J)
Olivia Reilly
(O)
Noureen Dhanani
(N)
Maria Amy Edridge
(MA)
Alisa Petit
(A)
Yarnick Mirjah
(Y)
Robert A Stern
(RA)
Jane Mwicigi
(J)
Alexa Puleio
(A)
Jesse Mez
(J)
Wendy Qiu
(W)
Eric Steinberg
(E)
Mark Brody
(M)
Paayal Patel
(P)
Cynthia Stimeck
(C)
Stephen P Salloway
(SP)
Diane Monast
(D)
Vanessa Rua
(V)
Sophia Tarro
(S)
Jessica Alber
(J)
Athene K W Lee
(AKW)
Gad A Marshall
(GA)
Tia Hall
(T)
Emily Sprague
(E)
Mariana Palou
(M)
Martha Vander Vliet
(M)
Dorene M Rentz
(DM)
Michael Karathanos
(M)
Christy Lisenbee
(C)
Sarah Land
(S)
Carmen Toegel
(C)
Dylan Wint
(D)
Charles Bernick
(C)
Michelle Torreliza
(M)
Simrit Saraon
(S)
Barnett Shpritz
(B)
Karen L Bell
(KL)
Ruth Tejeda
(R)
Chrismary De La Cruz
(C)
Lawrence Honig
(L)
Betina Idnay
(B)
Horacio A Capote
(HA)
Michelle Rainka
(M)
Traci Aladeen
(T)
Tatiana Jimenez-Knight
(T)
Heather MacNamara
(H)
G Peter Gliebus
(GP)
Katherine Rife
(K)
Melinda Webster
(M)
Christine Barr
(C)
Monica Mazurek
(M)
James J Lah
(JJ)
Allan I Levey
(AI)
Deborah Westover
(D)
Gail Schwartz
(G)
Lauren Mariotti
(L)
Raymond Scott Turner
(RS)
Melanie Chadwick
(M)
Kathleen Johnson
(K)
Brigid Reynolds
(B)
Kelly McCann
(K)
Jeffrey Ross
(J)
Linda Rice
(L)
Thomas O Obisesan
(TO)
Oyonumo E Ntekim
(OE)
Sheeba R Nadarajah
(SR)
Sharlene Leong
(S)
Jillian Turner
(J)
Saba Wolday
(S)
Mary Sano
(M)
Judith Neugroschl
(J)
Joanne Lim
(J)
Allison Ardolino
(A)
Gina Garcia Camilo
(G)
Amy Aloyisi
(A)
Martin Farlow
(M)
Jared Brosch
(J)
Nancy McClaskey
(N)
Paul B Rosenberg
(PB)
Meghan Schultz
(M)
Samantha Schwartz
(S)
Samantha Horn
(S)
Mersania Jn Pierre
(M)
Neill R Graff-Radford
(NR)
Christopher Homa
(C)
Amanda Phillips
(A)
David S Knopman
(DS)
Bronwyn Briseno
(B)
Jonathan Graff Radford
(J)
Sara Mason
(S)
Karen Kuntz
(K)
Kari Baxter
(K)
Joseph C Masdeu
(JC)
Belen Pascual
(B)
Mica Mangibin
(M)
Benjamin Batista
(B)
Sandra Weintraub
(S)
Ian Grant
(I)
Brittanie Muse
(B)
Shea Gold
(S)
Jelena Pejic
(J)
Loreece Haddad
(L)
Melanie Shulman
(M)
Anaztasia Ulysse
(A)
Jamika Singleton-Garvin
(J)
Mohammed Sheikh
(M)
Mrunaliniash Gaikwad
(M)
Aimee L Pierce
(AL)
Lisa C Silbert
(LC)
Steven Aurich
(S)
Jeffrey A Kaye
(JA)
Alexandra A Ruhf
(AA)
Amy B Thomas
(AB)
Jeffrey N Keller
(JN)
William P Gahan
(WP)
Robert Brouillette
(R)
Heather Foil
(H)
Owen Carmichael
(O)
Paul Winner
(P)
Alfonso X Moreno
(AX)
Brian R Ott
(BR)
Chuang-Kuo Wu
(CK)
Hannah Alaimo
(H)
Lori A Daiello
(LA)
Jonathan D Drake
(JD)
Alisa Omert
(A)
Jacobo Mintzer
(J)
Olga Brawman-Mintzer
(O)
Allison Acree
(A)
Heather Allen
(H)
Arthur Williams
(A)
Neelum T Aggarwal
(NT)
Ajay Sood
(A)
Kimberly Blanchard
(K)
Peter Lambiotis
(P)
Amelia Troutman
(A)
Elaine Peskind
(E)
James O'Connell
(J)
Adam McPartlin
(A)
Murray A Raskind
(MA)
Anita Ranta
(A)
Jerome Yesavage
(J)
Steven Z Chao
(SZ)
Tamara Beale
(T)
Jaila Coleman
(J)
Shawn Kile
(S)
Valentina Mikhalenko
(V)
Yvonne Au
(Y)
Mary Vaughn
(M)
Sampreet Moneski
(S)
Tammy Donnell
(T)
Dawn Lenakakis
(D)
John Gregory Duffy
(JG)
Lorrie Bisesi
(L)
Poonam Nina Banerjee
(PN)
Maria Gonzalez
(M)
Rania Bilwani
(R)
Alan J Lerner
(AJ)
Maria Toth
(M)
Parianne Fatica
(P)
Susie Sami
(S)
Paula Ogrocki
(P)
Marianne Sanders
(M)
Marissa C Natelson Love
(MC)
P Denise Ledlow
(PD)
Amber Watkins
(A)
David S Geldmacher
(DS)
Loren Brown Ashley
(L)
Jacqueline Vaughn
(J)
John Olichney
(J)
Charles DeCarli
(C)
Hongzheng Zhang
(H)
Antoinette Lopez
(A)
Mary McPhail-Ciufo
(M)
Adrian Preda
(A)
Andrea Weideman
(A)
Steven Potkin
(S)
Melanie Tallakson
(M)
Catherine McAdams-Ortiz
(C)
Beatriz Vides
(B)
Gaby T Thai
(GT)
Steven P Tam
(SP)
Maryam Beigi
(M)
Thao Rodriguez
(T)
Maya Farchi
(M)
Roberto Hernandez
(R)
Lorena Monserratt
(L)
Lauren Garcia
(L)
Celine Ossinalde
(C)
Douglas Galasko
(D)
Helen Vanderswag
(H)
Laura Linares
(L)
Chi Kim
(C)
Shawnees Peacock
(S)
Adam L Boxer
(AL)
Lawren Vandevrede
(L)
Peter Ljubenkov
(P)
Julio C Rojas
(JC)
Del D Miller
(DD)
Hristina K Koleva
(HK)
Karen Ekstam Smith
(K)
Laura Temple
(L)
Susan Schultz
(S)
Anne Arthur
(A)
Rachel Starr
(R)
Nicole Mathis
(N)
Phyllis Switzer
(P)
Gregory A Jicha
(GA)
Andrea L Shaffer
(AL)
Sarah Hatch
(S)
Sierra Fuhrmann
(S)
Molly Harper
(M)
Kelly Parsons
(K)
Jaimie Ziolkowski
(J)
Judith L Heidebrink
(JL)
Bekkie Wang
(B)
Daniel L Murman
(DL)
Haley Kampschneider
(H)
Deb Heimes
(D)
Nick Miller
(N)
Sanjeev N Vaishnavi
(SN)
Martha Combs
(M)
Jade Uffelman
(J)
Loren Terrill
(L)
Oscar Lopez
(O)
Thomas Baumgartner
(T)
Sarah Goldberg
(S)
Donna Simpson
(D)
Cary Zik
(C)
Anton P Porsteinsson
(AP)
Audrey Rice
(A)
Susan Salem-Spencer
(S)
Bridget Holvey
(B)
Asa Widman
(A)
Mauricio Becerra
(M)
Liberty Teodoro
(L)
Sonia Pawluczyk
(S)
Karen Dagerman
(K)
Lon Schneider
(L)
Brendan Kelley
(B)
Shahera Ranjha
(S)
Jana Windsor
(J)
Mary Quiceno
(M)
Cynthia M Carlsson
(CM)
Benjamin Farral
(B)
Kim Peterson
(K)
Sandra Harding
(S)
Aleshia Cole
(A)
Amanda G Smith
(AG)
Juris Jarvis
(J)
Breanna Davis
(B)
Kelly Rodrigo
(K)
Ijeoma Mba
(I)
Anna D Sladky
(AD)
Patricia Lowe
(P)
Suzanne Craft
(S)
Abigail Heston O'Connell
(A)
Alexis Web
(A)
Bevan Hoover
(B)
Patricia Wittmer
(P)
Randall Bateman
(R)
Joy Snider
(J)
Gregory Day
(G)
Nupur Ghoshal
(N)
Erik Musiek
(E)
Tammie Benzinger
(T)
John Morris
(J)
Marta Santos
(M)
Michael Lin
(M)
Norman Relkin
(N)
Ranjan Duara
(R)
Maria T Greig Custo
(MT)
Rosemarie A Rodriguez
(RA)
Julieth Formosa
(J)
Warren Barker
(W)
Cesar Chirinos
(C)
Joyce Lee
(J)
Christopher H van Dyck
(CH)
Julia W McDonald
(JW)
Susan P Good
(SP)
Joanna E Harris
(JE)
Kara Bates
(K)
Jessica Lam
(J)
Informations de copyright
Copyright © 2023 Massachusetts Medical Society.
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