Active not recruitingPhase 1 / PHASE2

Brainshuttle AD: A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Participants With Prodromal or Mild to Moderate Alzheimer's Disease

A Phase Ib/IIa, Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Patients With Prodromal or Mild to Moderate Alzheimer's Disease

Lead sponsor

Hoffmann-La Roche

Asset

Trontinemab

Listed sites

Recruiting sites

Enrollment

241

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MCI due to AD / prodromal AD / mild-to-moderate AD / moderate AD dementia•Amyloid biomarker required (PET)•MMSE 18-28•Study partner/caregiver required•MRI contraindications excluded

Primary endpoints

•Part 1, 2, 3, and 4•Part 3

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

Eudract number2020-002477-98

Secondary ID2023-509678-52-00EU Trial Number

Org study IDBP42155

NCT IDNCT04639050

Timeline

Milestones

Study first posted2020-11-20actual

Study start2021-03-15actual

Last update posted2026-06-16actual

Primary completion2027-07-31estimated

Study completion2027-07-31estimated

Assets

Drug assets

Trontinemab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Key inclusion criteria for part 1, 2 and 3:

•Ability to provide written consent signed by the participant

•Availability of a person (referred to as the "study partner") who: consents to participate throughout the duration of study, in the Investigator's judgment, has frequent and sufficient contact with the participant, is fluent in the language of the tests used at the study site

•Willingness and ability to complete all aspects of the study (including magnetic resonance imaging [MRI], lumbar puncture, clinical genotyping, and positron emission tomography [PET] imaging)

•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 (eye glasses and hearing aids are permitted)

•Probable mild to moderate AD dementia (consistent with National Institute on Aging-Alzheimer's Association [NIA-AA] core clinical criteria for probable AD dementia) or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD)

•Screening Mini-Mental State Examination (MMSE) score of 18 to 28 points, inclusive, within 84 days before baseline

•Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1, or 2 within 84 days before baseline

•Positive amyloid PET scan (cut-off: >50 Centiloid units) within 12 months before baseline

•In case of treatment with symptomatic AD medications, dosing regimen must be stable for at least 8 weeks prior to baseline and until randomization

•Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug

•Agreement not to participate in other research studies for the duration of this study

•Agree to apolipoprotein E (APOE) genotyping

Inclusion criteria for Part 4:

- Completed the treatment period in Part 1, Part 2, or Part 3 of the study

Exclusion criteria

for part 1, 2 and 3:

•Any evidence of other relevant neurological condition, including other (non-AD) neurodegenerative and neuropsychiatric conditions, neurovascular brain disorders, seizure disorders, inflammatory and infectious disorders of the central nervous system, trauma and delirium, among several others

•Other relevant medical conditions including significant hematological diseases, any clinically significant ophthalmologic diseases, decreased visual acuity in either eye, with a BCVA letter score of less than 20 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or the Snellen equivalent of 20/400 if the ETDRS chart is not used

•Clinically significant cardiovascular diseases, chronic kidney disease, confirmed and unexplained impaired hepatic function, abnormal thyroid function, among several others

•History of hypersensitivity to biologic agents or any of the excipients in the formulation

•Clinically significant abnormalities (as judged by the Investigator) in laboratory test results (including complete blood count, chemistry panel, routine cerebrospinal fluid [CSF] parameters and urinalysis)

•MRI exclusion criteria: >2 lacunar infarcts (including lacunar infarcts in the cerebellum), any territorial infarct >1 cm^3, any white matter lesion that corresponds to an overall Fazekas score of 3 that requires at least one confluent hyperintense lesion on the fluid-attenuated inversion recovery (FLAIR) sequence, which is ≥20 mm in any dimension

•More than 4 microhemorrhages on MRI and/or presence of any focal area of leptomeningeal hemosiderosis based on the review performed by the central MRI reader prior to randomization

•Presence of any other significant cerebral abnormalities, including amyloid-related imaging abnormality-edema/effusion (ARIA-E), as assessed on MRI

•Inability to tolerate MRI procedures or contraindication to MRI

•Inability to undergo ophthalmological assessments

•Contraindication to lumbar puncture

•Contraindication to having a PET scan

Exclusion criteria for Part 4:

•Prematurely discontinued from the treatment period for study (i.e., before the start of the follow-up period of Part 1, Part 2, or Part 3) for any reason or meeting discontinuation criteria before the baseline visit of Part 4.

•Received any active investigational treatment other than RO7126209 during or since completion of Part 1, Part 2 or Part 3

•Any passive immunotherapy (immunoglobulin) since completion of Part 1, Part 2, or Part 3 that is meant to prevent or postpone cognitive decline.

•Use of anti-coagulation medications - Evidence of ongoing ARIA-E. In this case participant may enroll into Part 4 once the ARIA-E is resolved - Evidence of ongoing infusion-related reaction (IRR) or hypersensitivity reaction. In this case participant may enroll into Part 4 once the IRR is resolved.

•MRI evidence of any of the following at OLE baseline: evidence of ongoing ARIA-E, any ARIA-H (leptomeningeal hemosiderosis or microhemorrhages) that would require permanent discontinuation of study treatment, > 2 lacunar infarcts, Any territorial infarct > 1 cm^3, any white matter lesion that corresponds to an overall Fazekas score of 3 that requires at least one confluent hyperintense lesion on the FLAIR sequence, which is ≥ 20 mm in any dimension

•Any drop in hemoglobin of > 20% compared to predose on Day 1 or hemoglobin value below 10 g/dL

Endpoints (6)

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

Amyloid biomarkers

Safety / tolerability / PK

Fluid / digital biomarkers

Other (unclassified)

Amyloid biomarkers

2 endpoints

Primary/protocol endpoint

Part 3: Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan

Time frame:Up to approximately 24 weeks

change from baseline, improvement

Secondary/protocol endpoint

Part 1, 2, and 4: Change From Baseline in Brain Amyloid Load as Measured by Amyloid PET Scan

Time frame:Part 1 and 2: Up to approximately 28 weeks; Part 4: Up to approximately 205 weeks

change from baseline, improvement

Fluid / digital biomarkers

1 endpoint

Secondary/protocol endpoint

Part 1, 2, 3, and 4: Cerebral Spinal Fluid (CSF) Concentration of RO7126209

Time frame:Part 1 and 2: Up to approximately 25 weeks; Part 3: Up to approximately 21 weeks; Part 4: Up to approximately 205 weeks

concentration, descriptive

Safety / tolerability / PK

2 endpoints

Primary/protocol endpoint

Part 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs)

Time frame:Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks

threshold achievement, event

Secondary/protocol endpoint

Part 1, 2, 3, and 4: Plasma Concentration of RO7126209

Time frame:Part 1 and 2: Up to approximately 32 weeks; Part 3: Up to approximately 24 weeks; Part 4: Up to approximately 209 weeks

concentration, descriptive

Other (unclassified)

1 endpoint

Secondary/protocol endpoint/low confidence

Part 1, 2, 3, and 4: Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209

Time frame:Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks

event count, event

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.