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

June 15, 2026 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

241

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Heidelberg West, Victoria, Australia, 3081
        • Heidelberg Repatriation Hospital
      • Melbourne, Victoria, Australia, 3004
        • Alfred Hospital
  • Canada
    • British Columbia
      • Richmond, British Columbia, Canada, V6V 2L1
        • Richmond Clinical Trials
    • Ontario
      • Toronto, Ontario, Canada, M3B 2S7
        • Toronto Memory Program
  • Chile
      • Santiago, Chile, 8330034
        • Centro de Investigación Clínica UC-CICUC
      • Santiago, Chile, 8380456
        • Hospital Clinico Univ de Chile
  • Japan
      • Kanagawa, Japan, 231-8682
        • Yokohama City Minato Red Cross Hospital
      • Kyoto, Japan, 616-8255
        • National hospital Organization Utano National Hospital
      • Kyoto, Japan, 600-8558
        • Koseikai Takeda Hospital
      • Tokyo, Japan, 160-8582
        • Keio University Hospital
      • Tokyo, Japan, 190-8531
        • Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital
      • Tokyo, Japan, 173-0015
        • Tokyo Metropolitan Institute for Geriatrics and Gerontology
  • Poland
      • Szczecin, Poland, 70-111
        • Osrodek Badan Klinicznych Euromedis
      • Wroc?aw, Poland, 53-659
        • NZOZ WCA
  • South Korea
      • Incheon, South Korea, 22332
        • Inha University Hospital
      • Seoul, South Korea, 06351
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial
      • Barcelona, Spain, 08028
        • Fundación ACE
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Valencia, Spain, 46017
        • Hospital Universitario Dr. Peset
      • Valencia, Spain, 46026
        • Hospital Universitario La Fe
    • Barcelona
      • Sant Cugat del Vallès, Barcelona, Spain, 8195
        • Hospital General de Catalunya
    • Guipuzcoa
      • Donostia / San Sebastian, Guipuzcoa, Spain, 20014
        • Policlínica Guipuzcoa
  • United Kingdom
      • London, United Kingdom, WC1N 3BG
        • UCL Institute of Neurology
  • United States
    • Florida
      • Atlantis, Florida, United States, 33462
        • JEM Research LLC
      • Clermont, Florida, United States, 34711
        • K2 Medical Research-Winter Garden
      • Lady Lake, Florida, United States, 32159
        • K2 Medical Research - The Villages
      • Maitland, Florida, United States, 32751
        • K2 Medical Research, LLC
      • Miami, Florida, United States, 33135
        • Optimus U Corp
      • Orlando, Florida, United States, 32804
        • Advent Health Orlando
      • Orlando, Florida, United States, 32803
        • Charter Research - Winter Park/Orlando
      • Stuart, Florida, United States, 34996
        • Alzheimer's Research and Treatment Center
      • The Villages, Florida, United States, 32162
        • Charter Research - Lady Lake/The Villages
      • Wellington, Florida, United States, 33414
        • Alzheimer?s Research and Treatment Center
      • Winter Park, Florida, United States, 32789
        • Conquest Research, LLC
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Alzheimer's Research and Treatment Center - Columbus
      • Gainesville, Georgia, United States, 30501
        • Center for Advanced Research & Education
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Quest Research Institute
    • Oregon
      • Portland, Oregon, United States, 97210
        • Summit Research Network Inc.
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Neurological Associates
    • Texas
      • Dallas, Texas, United States, 75231
        • Kerwin Research Center, LLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Key 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: 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.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102
Placebo Comparator: 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.
Drug: Placebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Other Names:
  • RO727-5887, F01-01
Experimental: Part 4: Open Label Extension (OLE)
Participants who completed Part 1, 2, or 3 will receive RO7126209 for a maximum of 205 weeks.
Drug: RO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
Other Names:
  • Trontinemab
  • RG6102

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Up to approximately 24 weeks
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
Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Part 1 and 2: Up to approximately 28 weeks; Part 4: Up to approximately 205 weeks
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
Part 1 and 2: Up to approximately 32 weeks; Part 3: Up to approximately 24 weeks; Part 4: Up to approximately 209 weeks
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
Part 1 and 2: Up to approximately 25 weeks; Part 3: Up to approximately 21 weeks; Part 4: Up to approximately 205 weeks
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
Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2021

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

November 17, 2020

First Submitted That Met QC Criteria

November 17, 2020

First Posted (Actual)

November 20, 2020

Study Record Updates

Last Update Posted (Actual)

June 16, 2026

Last Update Submitted That Met QC Criteria

June 15, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BP42155
  • 2020-002477-98 (EudraCT Number)
  • 2023-509678-52-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe