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

NCT04639050 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: BP421552020-002477-982023-509678-52-00
• Study Type: interventional
• Target: 241
• Locations: 9 countries
• Sites: 41

Brief Summary

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.

Conditions

Alzheimers Disease

Outcome Measures

Primary Outcomes (2)

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

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

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

  Up to approximately 24 weeks

Secondary Outcomes (4)

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

  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

  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

  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

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

Study Arms (19)

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

EXPERIMENTAL

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

Part 1 (Dose Finding) Cohort 1: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Part 1 (Dose Finding) Cohort 2: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Part 1 (Dose Finding) Cohort 3: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Part 1 (Dose Finding) Cohort 4: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Part 1 (Dose Finding) Cohort 5: Placebo

PLACEBO COMPARATOR

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

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

EXPERIMENTAL

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

Part 2 (Expansion) Cohort 1: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Part 2 (Expansion) Cohort 2: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

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

EXPERIMENTAL

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

Part 2 (Expansion) Cohort 3: Placebo

PLACEBO COMPARATOR

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Part 4: Open Label Extension (OLE)

EXPERIMENTAL

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

Drug: RO7126209

Interventions

RO7126209 DRUG

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

Also known as: Trontinemab, RG6102

Part 1 (Dose Finding) Cohort 1: Dose Level 1 of RO7126209; Part 1 (Dose Finding) Cohort 2: Dose Level 2 of RO7126209; Part 1 (Dose Finding) Cohort 3: Dose Level 3 of RO7126209; Part 1 (Dose Finding) Cohort 4: Dose Level 4 of RO7126209; Part 1 (Dose Finding) Cohort 5: Dose Level 5 of RO7126209; Part 2 (Expansion) Cohort 1: Dose Level 3 of RO7126209; Part 2 (Expansion) Cohort 2: Dose Level 4 of RO7126209; Part 2 (Expansion) Cohort 3: Dose Level 5 of RO7126209; Part 3 (Dose/Frequency/Pharmacodynamic (PD) Relationship): Dose Level 1: RO7126209; Part 3 Dose/Frequency/PD Relationship: Dose Level 2: RO7126209; Part 4: Open Label Extension (OLE)

Placebo DRUG

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

Also known as: RO727-5887, F01-01

Part 1 (Dose Finding) Cohort 1: Placebo; Part 1 (Dose Finding) Cohort 2: Placebo; Part 1 (Dose Finding) Cohort 3: Placebo; Part 1 (Dose Finding) Cohort 4: Placebo; Part 1 (Dose Finding) Cohort 5: Placebo; Part 2 (Expansion) Cohort 1: Placebo; Part 2 (Expansion) Cohort 2: Placebo; Part 2 (Expansion) Cohort 3: Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (41)

JEM Research LLC

Atlantis, Florida, 33462, United States

Location

K2 Medical Research-Winter Garden

Clermont, Florida, 34711, United States

Location

K2 Medical Research - The Villages

Lady Lake, Florida, 32159, United States

Location

K2 Medical Research, LLC

Maitland, Florida, 32751, United States

Location

Optimus U Corp

Miami, Florida, 33135, United States

Location

Charter Research - Winter Park/Orlando

Orlando, Florida, 32803, United States

Location

Advent Health Orlando

Orlando, Florida, 32804, United States

Location

Alzheimer's Research and Treatment Center

Stuart, Florida, 34997, United States

Location

Charter Research - Lady Lake/The Villages

The Villages, Florida, 32162, United States

Location

Alzheimer?s Research and Treatment Center

Wellington, Florida, 33414, United States

Location

Conquest Research, LLC

Winter Park, Florida, 32789, United States

Location

Alzheimer's Research and Treatment Center - Columbus

Columbus, Georgia, 31904, United States

Location

Center for Advanced Research & Education

Gainesville, Georgia, 30501, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Summit Research Network Inc.

Portland, Oregon, 97210, United States

Location

Abington Neurological Associates

Abington, Pennsylvania, 19001, United States

Location

Kerwin Research Center, LLC

Dallas, Texas, 75231, United States

Location

Heidelberg Repatriation Hospital

Heidelberg West, Victoria, 3081, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Richmond Clinical Trials

Richmond, British Columbia, V6V 2L1, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Centro de Investigación Clínica UC-CICUC

Santiago, 8330034, Chile

Location

Hospital Clinico Univ de Chile

Santiago, 8380456, Chile

Location

Yokohama City Minato Red Cross Hospital

Kanagawa, 231-8682, Japan

Location

Koseikai Takeda Hospital

Kyoto, 600-8558, Japan

Location

National Hospital Organization Utano National Hospital

Kyoto, 616-8255, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

Tokyo Metropolitan Geriatric Hospital

Tokyo, 173-0015, Japan

Location

Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital

Tokyo, 190-8531, Japan

Location

Osrodek Badan Klinicznych Euromedis

Szczecin, 70-111, Poland

Location

NZOZ WCA

Wroc?aw, 53-659, Poland

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital General De Catalunya

Sant Cugat del Vallès, Barcelona, 8195, Spain

Location

Policlínica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Fundación ACE

Barcelona, 08028, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Hospital Universitario la Fe

Valencia, 46026, Spain

Location

UCL Institute of Neurology

London, WC1N 3BG, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 20, 2020
• Study Start: March 15, 2021
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (2); CA (2); AU (2); CL (2); PL (2); ES (7); US (17); GB (1); JP (6)