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NCT07717411PHASE3Recruiting

A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease

Hoffmann-La Roche

Start Date

11/30/2026

Completion Date

9/3/2032

Summary

This study will evaluate the efficacy and safety of trontinemab in participants with biomarker evidence of Alzheimer's Disease (AD) pathology but with no cognitive or functional impairment, who are at risk for progression to mild cognitive impairment (MCI) due to AD or dementia due to AD.

Eligibility Criteria

Age Range: 55 years to 80 years

Inclusion Criteria: * Body weight of 150 kg or less * Willingness and ability to complete all aspects of the study for the duration of the study * Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eyewear and hearing aids are permitted) * Cognitively and functionally unimpaired as defined by the protocol * Availability of a study partner as defined by the protocol * A plasma pTau217 level consistent with a high likelihood of future clinical progression Exclusion Criteria: * Any evidence of a condition other than AD that may affect cognition, including, but not limited to, frontotemporal dementia, dementia with Lewy bodies, vascular dementia, Parkinson disease, corticobasal syndrome, Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal lobar degeneration (other than frontotemporal dementia), Huntington disease, normal pressure hydrocephalus, seizure disorder, delirium, or hypoxia * Mild cognitive impairment (MCI; may be referred to as prodromal AD), or any form of dementia * 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 * History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder * History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 12 months of an acute event that is consistent, in the opinion of the PI, with a transient ischemic attack * At risk for suicide in the opinion of the investigator * Substance abuse disorder within 12 months prior to screening (nicotine use is allowed) * 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 * Uncontrolled hypertension * Impaired hepatic function * History or presence of any clinically significant hematological diseases * Diagnosis of a wet age-related macular degeneration (AMD) * Abnormal thyroid function * Abnormally low serum levels of folic acid or vitamin B12 deficiency that are judged to be clinically significant and/or may impact cognition as per the investigator's judgment * Current HIV, hepatitis B, or hepatitis C infection that has not been adequately treated in the opinion of the investigator * History of malignancy * Any previous administration of active immunotherapy (vaccine) that is being evaluated to prevent or postpone cognitive decline * Any previous or current use of passive immunotherapy (immunoglobulin) or other long-acting biologic agent that is approved or under evaluation or has been evaluated to prevent or postpone cognitive decline * Any other investigational treatment within 5 half-lives or 4 months prior to screening, whichever is longer * Intravenous (IV) or subcutaneous immunoglobulin therapy within 5 half-lives or 4 months prior to baseline whichever is longer * Anticoagulation medications at screening and there should be no plans to initiate any prior to or after randomization * Any treatment with cholinesterase inhibitors * Antipsychotic or neuroleptic medications within 3 months of screening, except as brief treatment for a non-psychiatric indication * Individuals with chronic use of opiates or opioids, benzodiazepines, barbiturates, or hypnotics, antidepressants or medication to treat anxiety should be on a stable dose for at least 8 weeks before baseline * Currently enrolled in an interventional study including those requiring investigational medicinal product (IMP) or involving any type of medical research that may interfere with study cognitive assessments * Residence in a skilled nursing facility such as a convalescent home or long-term care facility

Interventions

DRUG

Trontinemab

DRUG

Placebo

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Conditions

Alzheimer's Disease

Locations

Irvine Center for Clinical Research

Irvine, California 92614

United States

Healthy Brain Clinic

Long Beach, California 90804

United States

Oakland Clinical

Oakland, California 94609

United States

Syrentis Clinical Research

Santa Ana, California 92705

United States

K2 Medical Research, LLC

Maitland, Florida 32751

United States

Renstar Medical Research

Ocala, Florida 34470

United States

Charter Research - Winter Park/Orlando

Orlando, Florida 32803

United States

Conquest Research - Lake Nona

Orlando, Florida 32832

United States

Charter Research - Lady Lake/The Villages

The Villages, Florida 32162

United States

Conquest Research, LLC

Winter Park, Florida 32789

United States

Basil Clinical

Laurelton, New York 11413-2016

United States

Sana Research, LLC

Arlington, Virginia 22205

United States

Hospital Italiano de Buenos Aires

Buenos Aires, C1181ACH

Argentina

Royal Prince Alfred Hospital

Camperdown, New South Wales 2050

Australia

KaRa Institute of Neurological Diseases

Macquarie Park, New South Wales 2113

Australia

Kelowna Health and Memory Centre Ltd.

Kelowna, British Columbia V1Y 5A8

Canada

Toronto Memory Program

Toronto, Ontario M3B 2S7

Canada

The second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong 510260

China

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei 050031

China

Yan'an University Xianyang Hospital

Xianyang, Shaanxi 712000

China

Beijing Friendship Hospital Affiliated of Capital University of Medical Science

Beijing, 100050

China

Xuanwu Hospital, Capital Medical University

Beijing, 100053

China

Sir Run Run Shaw Hospital Zhejiang University

Hangzhou, 310016

China

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, 210003

China

Nanjing First Hospital

Nanjing, 210029

China

The Second Affiliated Hospital of Suzhou University

Suzhou, 215025

China

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Scottish Brain Sciences

Aberdeen, AB25 2XE

United Kingdom

Re:Cognition Health Birmingham

Birmingham, B16 8QQ

United Kingdom

Surrey and Borders NHS Foundation Trust

Chertsey, KT16 9AU

United Kingdom

Scottish Brain Sciences

Edinburgh, EH12 5PJ

United Kingdom

Re:Cognition Health London

London, W1G 8TB

United Kingdom

Charing Cross Hospital

London, W6 8RF

United Kingdom

Moorgreen Hospital

Southampton, SO30 3JB

United Kingdom