TRONTIER 1

RecruitingPhase 3

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

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)

Lead sponsor

Hoffmann-La Roche

Asset

Trontinemab

Listed sites

143

Recruiting sites

133

Enrollment

800

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•MCI due to AD•Amyloid biomarker required (PET/CSF)•MMSE ≥22•Study partner/caregiver required•MRI contraindications excluded

Primary endpoint

•Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Ctis2024-518006-40-00

NCT IDNCT07169578

Org study IDWN45443

Timeline

Milestones

Study first posted2025-09-12actual

Study start2025-09-17actual

Last update posted2026-07-02actual

Primary completion2028-06-07estimated

Study completion2028-06-07estimated

Assets

Drug assets

Trontinemab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (15)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Amyloid biomarkers

Other (unclassified)

Function / daily living

Tau biomarkers

Neurodegeneration biomarkers

Safety / tolerability / PK

Global cognition

5 endpoints

Primary/protocol endpoint

Change from baseline to Week 72 in Clinical Dementia Rating, Sum of Boxes (CDR-SB)

Time frame:Baseline - Week 72

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change from baseline through Week 72 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13)

Time frame:Baseline - Week 72

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change from baseline through Week 72 in Mini-Mental State Examination (MMSE)

Time frame:Baseline - Week 72

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change from baseline in CDR-SB

Time frame:Baseline up to but excluding Week 72

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Time to increase in Clinical Dementia Rating, Global Score (CDR-GS)

Time frame:Baseline - Week 72

time to event, event

Function / daily living

1 endpoint

Secondary/protocol endpoint

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

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Amyloid biomarkers

3 endpoints

Secondary/protocol endpoint

Percentage of participants with amyloid-related imaging abnormalities (ARIA) magnetic resonance imaging (MRI) findings

Time frame:Baseline - Week 72

threshold achievement, improvement

Secondary/protocol endpoint

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, improvement

Secondary/protocol endpoint

Change from baseline through Week 72 in cerebrospinal fluid (CSF) biomarkers of disease p-tau181, neurogranin, Aβ42 in a subset of participants

Time frame:Baseline - Week 72

Phosphorylated tau 181 (p-tau181)

change from baseline, improvement

Tau biomarkers

1 endpoint

Secondary/protocol endpoint

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

change from baseline, improvement

Neurodegeneration biomarkers

1 endpoint

Secondary/protocol endpoint

Change from baseline through Week 72 in blood biomarkers p-tau217, glial fibrillar acidic protein (GFAP)

Time frame:Baseline - Week 72

Phosphorylated tau 217 (p-tau217)

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Percentage of participants with adverse events (AEs)

Time frame:Baseline - Week 72

threshold achievement, event

Other (unclassified)

3 endpoints

Secondary/protocol endpoint/low confidence

Change from baseline through Week 72 in Integrated Alzheimer's Disease Rating Scale (iADRS)

Time frame:Baseline - Week 72

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Percentage of participants with infusion-related reactions (IRR)

Time frame:Baseline - Week 72

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Percentage of participants with anti-drug antibodies (ADAs) to trontinemab

Time frame:Baseline - Week 72

threshold achievement, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.