Alzheimers Disease
Conditions
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.
Interventions
DRUGRO7126209
RO7126209 will be administered intravenously as specified in each treatment arm.
DRUGPlacebo
RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| 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 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
| 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 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 |
Countries
Australia, Canada, Chile, Japan, Poland, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed