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

NCT ID: NCT04639050

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

241 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-15

Study Completion Date

2030-06-30

Brief Summary

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The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of multiple-ascending intravenous (IV) doses of RO7126209 in participants with prodromal or mild to moderate Alzheimer's disease (AD), who are amyloid positive based on amyloid positron emission tomography (PET) scan.

Detailed Description

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Conditions

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Alzheimers Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Part 1 (Dose Finding) Cohort 5: Placebo

Participants will receive a total of 2 doses of matching placebo to dose level 5 Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 2 (Expansion) Cohort 1: Dose Level 3 of RO7126209

Participants will receive multiple doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 2 (Expansion) Cohort 1: Placebo

Participants will receive matching placebo to dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 2 (Expansion) Cohort 2: Dose Level 4 of RO7126209

Participants will receive multiple doses of RO7126209 at dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 2 (Expansion) Cohort 2: Placebo

Participants will receive matching placebo to dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 2 (Expansion) Cohort 3: Dose Level 5 of RO7126209

Participants will receive a total of 2 doses of RO7126209 at dose level 5, Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 2 (Expansion) Cohort 3: Placebo

Participants will receive a total of 2 doses of matching placebo to dose level 5, Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 5: Dose Level 5 of RO7126209

Participants will receive a total of 2 doses of RO7126209 at dose level 5 Q4W, for 28 weeks followed by an 8-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 1: Dose Level 1 of RO7126209

Participants will receive multiple doses of RO7126209 at dose level 1 once every 4 weeks (Q4W) for 28 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 1: Placebo

Participants will receive matching placebo to dose level 1 Q4W for 28 weeks followed by a 28-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 2: Dose Level 2 of RO7126209

Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 2: Placebo

Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 3: Dose Level 3 of RO7126209

Participants will receive multiple doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 3: Placebo

Participants will receive matching placebo to dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 4: Dose Level 4 of RO7126209

Participants will receive multiple doses of RO7126209 at dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 1 (Dose Finding) Cohort 4: Placebo

Participants will receive matching placebo to dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Part 3 (Dose/Frequency/Pharmacodynamic (PD) Relationship): Dose Level 1: RO7126209

Participants will receive multiple doses of RO7126209 in an open-label treatment period at dose level 1, Q4W, for 24 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 3 Dose/Frequency/PD Relationship: Dose Level 2: RO7126209

Participants will receive multiple doses of RO7126209 in an open-label treatment period at dose level 2, Q12W, for 24 weeks followed by a 28-week safety follow-up period.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Part 4: Open Label Extension (OLE)

Participants who completed Part 1, 2, or 3 will receive RO7126209 for a maximum of 205 weeks.

Group Type EXPERIMENTAL

RO7126209

Intervention Type DRUG

RO7126209 will be administered intravenously as specified in each treatment arm.

Interventions

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RO7126209

RO7126209 will be administered intravenously as specified in each treatment arm.

Intervention Type DRUG

Placebo

RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Intervention Type DRUG

Other Intervention Names

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Trontinemab RG6102 RO727-5887, F01-01

Eligibility Criteria

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Inclusion Criteria

* 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


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

Exclusion Criteria

* 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)
* 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


* 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
Minimum Eligible Age

50 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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JEM Research LLC

Atlantis, Florida, United States

Site Status

K2 Medical Research-Winter Garden

Clermont, Florida, United States

Site Status

K2 Medical Research - The Villages

Lady Lake, Florida, United States

Site Status

K2 Medical Research, LLC

Maitland, Florida, United States

Site Status

Optimus U Corp

Miami, Florida, United States

Site Status

Charter Research - Winter Park/Orlando

Orlando, Florida, United States

Site Status

Advent Health Orlando

Orlando, Florida, United States

Site Status

Alzheimer's Research and Treatment Center

Stuart, Florida, United States

Site Status

Charter Research - Lady Lake/The Villages

The Villages, Florida, United States

Site Status

Alzheimer?s Research and Treatment Center

Wellington, Florida, United States

Site Status

Conquest Research, LLC

Winter Park, Florida, United States

Site Status

Alzheimer's Research and Treatment Center - Columbus

Columbus, Georgia, United States

Site Status

Center for Advanced Research & Education

Gainesville, Georgia, United States

Site Status

Quest Research Institute

Farmington Hills, Michigan, United States

Site Status

Summit Research Network Inc.

Portland, Oregon, United States

Site Status

Abington Neurological Associates

Abington, Pennsylvania, United States

Site Status

Kerwin Research Center, LLC

Dallas, Texas, United States

Site Status

Heidelberg Repatriation Hospital

Heidelberg West, Victoria, Australia

Site Status

Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Richmond Clinical Trials

Richmond, British Columbia, Canada

Site Status

Toronto Memory Program

Toronto, Ontario, Canada

Site Status

Centro de Investigación Clínica UC-CICUC

Santiago, , Chile

Site Status

Hospital Clinico Univ de Chile

Santiago, , Chile

Site Status

Yokohama City Minato Red Cross Hospital

Kanagawa, , Japan

Site Status

Koseikai Takeda Hospital

Kyoto, , Japan

Site Status

National Hospital Organization Utano National Hospital

Kyoto, , Japan

Site Status

Keio University Hospital

Tokyo, , Japan

Site Status

Tokyo Metropolitan Geriatric Hospital

Tokyo, , Japan

Site Status

Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital

Tokyo, , Japan

Site Status

Osrodek Badan Klinicznych Euromedis

Szczecin, , Poland

Site Status

NZOZ WCA

Wroc?aw, , Poland

Site Status

Inha University Hospital

Incheon, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital General De Catalunya

Sant Cugat del Vallès, Barcelona, Spain

Site Status

Policlínica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, Spain

Site Status

Fundación ACE

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Dr. Peset

Valencia, , Spain

Site Status

Hospital Universitario la Fe

Valencia, , Spain

Site Status

UCL Institute of Neurology

London, , United Kingdom

Site Status

Countries

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United States Australia Canada Chile Japan Poland South Korea Spain United Kingdom

Other Identifiers

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2020-002477-98

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-509678-52-00

Identifier Type: OTHER

Identifier Source: secondary_id

BP42155

Identifier Type: -

Identifier Source: org_study_id