A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease

Official title

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (MCI to Mild Dementia Due to AD)

Overview

The purpose of this study is to assess the efficacy and safety of trontinemab in participants with early symptomatic Alzheimer's disease (AD) (mild cognitive impairment \[MCI\] to mild dementia due to AD).

Interventions

• Drug Trontinemab
  Participants will receive IV trontinemab
• Other Placebo
  Participants will receive IV placebo

Primary outcome measures

• Change from baseline to Week 72 in Clinical Dementia Rating, Sum of Boxes (CDR-SB) [Time frame: Baseline - Week 72]

Secondary outcome measures (12)

• Change from baseline through Week 72 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) [Time frame: Baseline - Week 72]
• Change from baseline through Week 72 in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) total score and instrumental score [Time frame: Baseline - Week 72]
• Change from baseline through Week 72 in Integrated Alzheimer's Disease Rating Scale (iADRS) [Time frame: Baseline - Week 72]
• Change from baseline through Week 72 in Mini-Mental State Examination (MMSE) [Time frame: Baseline - Week 72]
• Change from baseline in CDR-SB [Time frame: Baseline up to but excluding Week 72]
• Time to increase in Clinical Dementia Rating, Global Score (CDR-GS) [Time frame: Baseline - Week 72]
• Percentage of participants with adverse events (AEs) [Time frame: Baseline - Week 72]
• Percentage of participants with amyloid-related imaging abnormalities (ARIA) magnetic resonance imaging (MRI) findings [Time frame: Baseline - Week 72]
• Percentage of participants with infusion-related reactions (IRR) [Time frame: Baseline - Week 72]
• Percentage of participants with anti-drug antibodies (ADAs) to trontinemab [Time frame: Baseline - Week 72]
• Change from baseline through Week 72 in brain amyloid load as measured by amyloid positron emission tomography (PET) scan [Time frame: Baseline - Week 72]
• Change from baseline to Week 72 in brain tau load as measured by tau PET scan in a subset of participants [Time frame: Baseline - Week 72]

Eligibility criteria

Inclusion criteria

• Willingness and ability to complete all aspects of the study (including MRI, clinical genotyping, and PET imaging or CSF as applicable) for the duration of the study. The participant should be capable of completing assessments either alone or with the help of the study partner
• Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eyewear and hearing aids are permitted)
• Evidence of AD pathological process, as confirmed on amyloid PET scan. A CSF tau181/Aβ42 ratio may be used as an alternative option if amyloid PET is not available
• Probable AD dementia or MCI due to AD, also known as an Alzheimer's clinical syndrome clinical Stage 3 or Stage 4
• Screening MMSE score ≥ 22 and CDR-GS of 0.5 or 1.0
• Participant- and/or Informant-reported history of cognitive decline with gradual onset and progression over the last 1 year before screening
• A Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory Index (RBANS DMI) score of 85 or order
• Availability of a "study partner" as defined by the protocol

Exclusion criteria

• Any evidence of a condition other than AD that may affect cognition
• History or presence of clinically significant cerebrovascular disease
• History of severe, clinically significant (persistent neurologic deficit or structural brain damage) central nervous system (CNS) trauma
• History or presence of clinically significant intracranial mass
• MRI evidence of significant cerebral abnormalities or inability to tolerate MRI procedures or contraindication to MRI
• Any other medical conditions (e.g., cardiovascular, hepatic, renal disease) which are not stable and adequately controlled or which in the opinion of the investigator could affect the participant's safety in the study or interfere with the study assessments
• History of malignancy with the following exceptions: if considered to be cured; malignancies with a negligible risk of metastasis or death

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 33 centers

• Banner Alzheimer?s Institute — Phoenix
• Sun Valley Research Center, Inc. — Imperial
• Healthy Brain Clinic — Long Beach
• Oakland Clinical — Oakland
• Riverside Clinical — Riverside
• Cenexel California Neuroscience Research, LLC — Sherman Oaks
• Yale University — New Haven
• JEM Research LLC — Atlantis
• … and 25 more centers

Germany · 15 centers

• Universitaetsklinikum Erlangen — Erlangen
• Ambulates Gesundheitszentrum der Charité GmbH — Berlin
• ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic — Berlin
• German Center for Neurodegenerative Diseases (DZNE) — Bonn
• Universitätsklinikum Köln — Cologne
• Medizinische Fakultät Carl Gustav Carus — Dresden
• Universitätsklinikum des Saarlandes Klinik f. Psychiatrie und Psychotherapie — Homburg/Saar
• Universitätsklinikum Jena, Klinik für Neurologie — Jena
• … and 7 more centers

South Korea · 12 centers

Center list to be confirmed — check the primary protocol.

Poland · 11 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 11 centers

Center list to be confirmed — check the primary protocol.

Japan · 10 centers

Center list to be confirmed — check the primary protocol.

Australia · 9 centers

• Royal Prince Alfred Hospital — Camperdown
• Southern Neurology — Kogarah
• KaRa Institute of Neurological Diseases — Macquarie Park
• Flinders Medical Centre — Bedford Park
• Queen Elizabeth Hospital — Woodville
• Box Hill Hospital — Box Hill
• Austin Health — Heidelberg
• Alfred Hospital — Melbourne
• … and 1 more center

France · 9 centers

• CHU Amiens Hopital Sud — Amiens Cedex1
• Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin — Bordeaux
• Groupement Hospitalier Est - Hôpital Neurologique — Bron
• CHU Dupruytren - Limoges — Limoges
• Hopital Gui de Chauliac — Montpellier
• Ch Pitie Salpetriere — Paris
• CHU de Rouen Hopital — Rouen
• Hop Guillaume Et Rene Laennec — Saint-Herblain
• … and 1 more center

Canada · 8 centers

• Okanagan Clinical Trials — Kelowna
• Centricity Research — Halifax
• Parkwood Institute Main Building — London
• The Ottawa Memory Clinic — Ottawa
• Kawartha Centre - Redefining Healthy Aging — Peterborough
• Sunnybrook Health Sciences Centre — Toronto
• St. Michael's Hospital — Toronto
• Genge Partners Inc. — Montreal

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Brazil · 6 centers

• L2 Ip Instituto de Pesquisas Clinicas Ltda ME — Brasília
• Instituto de Neurologia de Curitiba — Curitiba
• Clinica Clinilive ltda — Maringá
• Instituto do Cerebro do Rio Grande do Sul — Porto Alegre
• Clinica Neurologica — Joinville
• CEMEC - Centro Multidisciplinar de Estudos Clínicos — São Bernardo do Campo

Italy · 5 centers

Center list to be confirmed — check the primary protocol.

Switzerland · 4 centers

Center list to be confirmed — check the primary protocol.

Argentina · 3 centers

• INECO Neurociencias Orono — Rosario
• CIER — C. A. B. A.
• Fundacion Scherbovsky — Mendoza

Denmark · 3 centers

• Aalborg Universitetshospital — Aalborg
• Aarhus Universitetshospital Skejby — Aarhus N
• Rigshospitalet, Hukommelsesklinikken — København Ø

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07170150 · WN45447

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗