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

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: Recruiting
• Conditions: Alzheimers Disease
• Intervention / Treatment: Drug: RO7126209; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 285
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP42155 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Victoria
    • Heidelberg West, Victoria, Australia, 3081
      • Recruiting
      • Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
    • Melbourne, Victoria, Australia, 3004
      • Active, not recruiting
      • Alfred Hospital; Department of Neurology
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Recruiting
      • Okanagan Clinical Trials
  • Ontario
    • Toronto, Ontario, Canada, M3B 2S7
      • Recruiting
      • Toronto Memory Program
• Chile
  • Santiago, Chile, 8330034
    • Recruiting
    • Centro de Investigacion Clinica UC-CICUC
  • Santiago, Chile
    • Recruiting
    • Hospital Clinico Univ de Chile
• Japan
  • Kanagawa, Japan, 231-8682
    • Recruiting
    • Yokohama City Minato Red Cross Hospital
  • Kyoto, Japan, 600-8558
    • Recruiting
    • Koseikai Takeda Hospital
  • Kyoto, Japan, 616-8255
    • Recruiting
    • National Hospital Organization Utano National Hospital; Neurology
  • Tokyo, Japan, 173-0015
    • Recruiting
    • Tokyo Metropolitan Geriatric Hospital
  • Tokyo, Japan, 190-8531
    • Recruiting
    • Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital
  • Tokyo, Japan, 160-8582
    • Active, not recruiting
    • Keio University Hospital; Neurology
• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Recruiting
    • Inha University Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
• Poland
  • Bydgoszcz, Poland, 85-079
    • Withdrawn
    • Vitamed Ga?aj i Cichomski Spó?ka Jawna
  • Pozna?, Poland, 61-731
    • Withdrawn
    • Clinical Research Center Sp. z o.o. MEDIC-R Spó?ka Komandytowa
  • Szczecin, Poland, 70-111
    • Recruiting
    • Osrodek Badan Klinicznych Euromedis
  • Wroc?aw, Poland, 53-659
    • Recruiting
    • NZOZ WCA
• Spain
  • Barcelona, Spain, 08028
    • Recruiting
    • Fundación ACE; Servicio de Neurología
  • Barcelona, Spain, 08036
    • Active, not recruiting
    • Hospital Clinic i Provincial; Servicio de Neurologia
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre; Servicio de Neurologia
  • Valencia, Spain, 46017
    • Recruiting
    • Hospital Universitario Dr. Peset; Servicio de Neurologia
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario la Fe; Servicio de Neurologia
  • Barcelona
    • Sant Cugat del Valles, Barcelona, Spain, 8195
      • Recruiting
      • Hospital General De Catalunya; Servicio de Neurologia
  • Guipuzcoa
    • Donostia-san Sebastian, Guipuzcoa, Spain, 20014
      • Recruiting
      • Policlínica Guipuzcoa; Servicio de Neurología
• United Kingdom
  • Birmingham, United Kingdom, B16 8QQ
    • Recruiting
    • Re-Cognition
  • Bristol, United Kingdom, BS32 4SY
    • Recruiting
    • Recognition Health Bristol
  • London, United Kingdom, W1G 9JF
    • Recruiting
    • Re:Cognition Health
  • London, United Kingdom, WC1N 3BG
    • Recruiting
    • UCL Institute of Neurology; QSMSC, RSH
• United States
  • Florida
    • Atlantis, Florida, United States, 33462
      • Active, not recruiting
      • JEM Research LLC
    • Clermont, Florida, United States, 34711
      • Recruiting
      • K2 Medical Research-Winter Garden
    • Delray Beach, Florida, United States, 33445
      • Withdrawn
      • Brain Matters Research, Inc.
    • Lady Lake, Florida, United States, 32159
      • Recruiting
      • K2 Medical Research - The Villages
    • Maitland, Florida, United States, 32751
      • Recruiting
      • K2 Medical Research, LLC
    • Miami, Florida, United States, 33125
      • Recruiting
      • Optimus U Corp
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Advent Health Orlando
    • Port Orange, Florida, United States, 32127
      • Withdrawn
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • Recruiting
      • Alzheimer's Research and Treatment Center
    • The Villages, Florida, United States, 32162
      • Recruiting
      • Charter Research - Lady Lake/The Villages
    • Wellington, Florida, United States, 33414
      • Recruiting
      • Alzheimer?s Research and Treatment Center
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Conquest Research, LLC
    • Winter Park, Florida, United States, 32792
      • Recruiting
      • Charter Research - Winter Park/Orlando
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Recruiting
      • Columbus Memory Center
    • Gainesville, Georgia, United States, 30501
      • Recruiting
      • Center for Advanced Research & Education
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Quest Research Institute
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Recruiting
      • Alzheimer's Memory Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Recruiting
      • Summit Research Network Inc.
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Terminated
      • Abington Neurological Associates
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Kerwin Research Center, LLC

Participation Criteria

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, 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
• Combined number of microhemorrhages and focal areas of leptomeningeal hemosiderosis (i.e., cumulative amyloid-related imaging abnormality-microhemorrhage/hemosiderin deposition [ARIA-H]) on MRI more than 5 (and should not include more than 3 focal areas 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.
• Any drop in hemoglobin of > 20% compared to predose on Day 1 or hemoglobin value below 10 g/dL

Study Plan

How is the study designed?

Design Details

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

Number of Arms

21

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.
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.
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.
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.
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 2 (Expansion) Cohort 1: Dose Level 1 of RO7126209; Participants will receive multiple doses of RO7126209 at dose level 1, 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.
Placebo Comparator: Part 2 (Expansion) 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 2 (Expansion) 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.
Placebo Comparator: Part 2 (Expansion) 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 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.
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.
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.
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 3: Dose Level 3 of RO7126209; Participants will receive a total of 2 doses of RO7126209 at dose level 3, 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.
Placebo Comparator: Part 2 (Expansion) Cohort 3: Placebo; Participants will receive a total of 2 doses of matching placebo to dose level 3, 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) phase Arm 1: RO7126209; Participants who completed Part 1, 2, or 3 and have reached amyloid negativity (≤ 24 centiloids) in either of the Study Parts or at the OLE baseline visit will receive RO7126209 Q12W for 101 weeks. The dose level will depend on the dose level in Part 1, 2, and 3.	Drug: RO7126209; RO7126209 will be administered intravenously as specified in each treatment arm.
Experimental: Part 4 OLE Phase Arm 2: RO7126209; Participants who completed Part 1, 2, or 3 and who are amyloid positive (≥24 centiloids) will receive RO7126209 Q4W for 12 weeks and will have to reach amyloid negativity (≤ 24 centiloids) before they can switch to Q12W dosing in an open-label treatment period of 89 weeks. The dose level will depend on the dose level received in Part 1,2, and 3.	Drug: RO7126209; RO7126209 will be administered intravenously as specified in each treatment arm.
Experimental: Part 4 OLE Phase Arm 3: RO7126209; Participants who completed Part 1, 2, or 3 and who are amyloid positive (≥24 centiloids) at week 12 of OLE will receive RO7126209 Q4W for an additional 12 weeks, before to switch to Q12W dosing for the remaining 77 weeks in an open-label treatment period. The dose level will depend on the dose level received in Part 1,2, and 3.	Drug: RO7126209; RO7126209 will be administered intravenously as specified in each treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 129 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 Outcome Measures

Outcome Measure	Time Frame
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 101 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 101 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 129 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 105 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 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): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• 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: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No