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
Alzheimers Disease
About this trial
This is an interventional treatment trial for Alzheimers Disease
Eligibility Criteria
Key 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 Alzheimer's Disease (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 3 months before baseline
- Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1, or 2 within 3 months 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
Key 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, 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
Sites / Locations
- JEM Research LLC
- Brain Matters Research, Inc.
- Progressive Medical Research
- Quest Research Institute
- Abington Neurological Associates
- Kerwin Research Center, LLCRecruiting
- Heidelberg Repatriation Hospital; Medical and Cognitive Research CentreRecruiting
- Alfred Hospital; Department of Neurology
- Yokohama City Minato Red Cross HospitalRecruiting
- Koseikai Takeda HospitalRecruiting
- National Hospital Organization Utano National Hospital; NeurologyRecruiting
- Keio University Hospital; Neurology
- Tokyo Metropolitan Geriatric HospitalRecruiting
- Federation of National Public Service Personnel Mutual Aid Associations Tachikawa HospitalRecruiting
- Osrodek Badan Klinicznych EuromedisRecruiting
- NZOZ WCARecruiting
- Hospital General De Catalunya; Servicio de NeurologiaRecruiting
- Fundación ACE; Servicio de Neurología
- Hospital Clinic i Provincial; Servicio de Neurologia
- Hospital Universitario Dr. Peset; Servicio de NeurologiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Part 1 (Dose Finding) Cohort 1: Dose Level 1 of RO7126209
Part 1 (Dose Finding) Cohort 1: Placebo
Part 1 (Dose Finding) Cohort 2: Dose Level 2 of RO7126209
Part 1 (Dose Finding) Cohort 2: Placebo
Part 1 (Dose Finding) Cohort 3: Dose Level 3 of RO7126209
Part 1 (Dose Finding) Cohort 3: Placebo
Part 1 (Dose Finding) Cohort 4: Dose Level 4 of RO7126209
Part 1 (Dose Finding) Cohort 4: Placebo
Part 2 (Expansion) Cohort 1: Dose Level 1 of RO7126209
Part 2 (Expansion) Cohort 1: Placebo
Part 2 (Expansion) Cohort 2: Dose Level 2 of RO7126209
Part 2 (Expansion) Cohort 2: Placebo
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) phase: 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.
Participants will receive matching placebo to dose level 1 Q4W for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive multiple doses of RO7126209 at dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive matching placebo to dose level 3, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive multiple doses of RO7126209 at dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive matching placebo to dose level 4, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive multiple doses of RO7126209 at dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive matching placebo to dose level 1, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive multiple doses of RO7126209 at dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
Participants will receive matching placebo to dose level 2, Q4W, for 28 weeks followed by a 28-week safety follow-up period.
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.
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.
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. Those 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 101 weeks followed by a 28-week safety follow-up period.