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
- Neurodegenerative Disorder
- Alzheimer's Disease (AD)
- Farmington Hills
- Lake Worth
- Sant Cugat del Vallès
- Shinjuku City
- The Villages
NCT04639050 2020-002477-98, 2023-504549-30-00 BP42155
The source of the below information is public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc.. It has been summarised and edited into simpler language. For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow these links to https://clinicaltrials.gov and/or https://euclinicaltrials.eu and/or https://www.isrctn.com.
The below information is taken directly from public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc., and has not been edited.
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.
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
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 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 baseline or hemoglobin value below 10 g/dL
For the latest version of this information please go to www.forpatients.roche.com