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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 via intravenous (IV) infusion, Q4W for a total of seven doses during 28 weeks of treatment.
|
| Placebo Comparator: 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
Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Other Names:
|
| Experimental: Cohort 2: Dose Level 2 of RO7126209 Participants will receive multiple doses of RO7126209 at dose level 2 once every 4 weeks (Q4W) for 28 weeks followed by a 28-week safety follow-up period. |
Drug: RO7126209
RO7126209 will be administered via intravenous (IV) infusion, Q4W for a total of seven doses during 28 weeks of treatment.
|
| Placebo Comparator: 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
Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Other Names:
|
| Experimental: Cohort 3: Dose Level 3 of RO7126209 Participants will receive multiple doses of RO7126209 at dose level 3 once every 4 weeks (Q4W) for 28 weeks followed by a 28-week safety follow-up period. |
Drug: RO7126209
RO7126209 will be administered via intravenous (IV) infusion, Q4W for a total of seven doses during 28 weeks of treatment.
|
| Placebo Comparator: 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
Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Other Names:
|
| Experimental: Cohort : Dose Level 4 of RO7126209 Participants will receive multiple doses of RO7126209 at dose level 4 once every 4 weeks (Q4W) for 28 weeks followed by a 28-week safety follow-up period. |
Drug: RO7126209
RO7126209 will be administered via intravenous (IV) infusion, Q4W for a total of seven doses during 28 weeks of treatment.
|
| Placebo Comparator: 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
Matching placebo will be administered via IV infusion, Q4W for a total of seven doses during 28 weeks of treatment.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Adverse Events (AEs), Including Dose-Limiting Adverse Events (DLAEs) [Up to 56 weeks]
Secondary Outcome Measures
- Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan [Baseline, Week 12 (Cohorts 3 and 4 only), Week 28]
- Plasma Concentration of RO7126209 [Up to 32 weeks]
- Cerebral Spinal Fluid (CSF) Concentration of RO7126209 [Baseline, Week 25]
- Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209 [Up to 56 weeks]
Eligibility Criteria
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
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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)
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Capable of completing assessments either alone or with the help of the study partner
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Adequate visual and auditory acuity, in the Investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
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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
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Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1, or 2 within 3 months before baseline
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Positive amyloid PET scan (cut-off: >50 Centiloid units) within 12 months before baseline
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In case of treatment with symptomatic AD medications, dosing regimen must be stable for at least 8 weeks prior to baseline and until randomization
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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
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Agreement not to participate in other research studies for the duration of this study
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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
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History of hypersensitivity to biologic agents or any of the excipients in the formulation
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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)
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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
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Contraindication to lumbar puncture
-
Contraindication to having a PET scan
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | JEM Research LLC | Atlantis | Florida | United States | 33462 |
| 2 | Brain Matters Research, Inc. | Delray Beach | Florida | United States | 33445 |
| 3 | Progressive Medical Research | Port Orange | Florida | United States | 32127 |
| 4 | Quest Research Institute | Farmington Hills | Michigan | United States | 48334 |
| 5 | Abington Neurological Associates | Abington | Pennsylvania | United States | 19001 |
| 6 | Kerwin Research Center, LLC; Kerwin Research Center, LLC | Dallas | Texas | United States | 75231 |
| 7 | Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre | Heidelberg West | Victoria | Australia | 3081 |
| 8 | Alfred Hospital; Department of Neurology | Melbourne | Victoria | Australia | 3004 |
| 9 | Osrodek Badan Klinicznych Euromedis | Szczecin | Poland | 70-111 | |
| 10 | NZOZ WCA | Wrocław | Poland | 53-659 | |
| 11 | Hospital General De Catalunya; Servicio de Neurologia | Sant Cugat del Valles | Barcelona | Spain | 8195 |
| 12 | Fundación ACE; Servicio de Neurología | Barcelona | Spain | 08028 | |
| 13 | Hospital Clinic i Provincial; Servicio de Neurologia | Barcelona | Spain | 08036 | |
| 14 | Hospital Universitario Dr. Peset; Servicio de Neurologia | Valencia | Spain | 46017 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BP42155
- 2020-002477-98