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This is a Phase I, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7105705 in two participant populations: healthy participants and participants with mild-to-moderate Alzheimer's disease. This study is a single dose, dose-escalation, and multiple dose study comprising approximately six single dose cohorts in healthy participants administered RO7105705, either intravenously (IV) or subcutaneously (SC), and comprising one or more multiple dose cohorts in healthy participants administered RO7105705 IV every week (QW), a total of 4 doses, and one or more multiple dose cohorts in participants with Alzheimer's disease administered RO7105705 IV QW, a total of 4 doses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Multiple Dose Placebo IV | Placebo Comparator | Healthy participants or participants with Alzheimer's disease will receive multiple doses of matching placebo IV QW, a total of 4 doses. |
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| Multiple Dose RO7105705 IV | Experimental | Healthy participants or participants with Alzheimer's disease will receive multiple doses of RO7105705 IV QW, a total of 4 doses. |
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| Single Dose RO7105705 SC | Experimental | Healthy participants will receive a single dose of RO7105705 SC on Day 1. |
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| Single dose Placebo IV | Placebo Comparator | Healthy participants will receive a single dose of placebo IV on Day 1. |
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| Single dose RO7105705 IV | Experimental | Healthy participants will receive a single dose of RO7105705 IV on Day 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Participants will receive single or multiple doses of RO7105705 matching placebo IV. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events | Screening up to Day 134 | |
| Number of Participants with Dose Limiting Adverse Events (DLAEs) | Day 1 up to Day 36 | |
| Change from Baseline in Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score | Baseline, up to approximately 134 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 19 in Global Function as Assessed Using the Clinical Dementia Rating (CDR) Global Score in Alzheimer's Disease Participants | Baseline, Week 19 | |
| Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) | Baseline, Days 29, 57, 113 |
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Inclusion Criteria:
All participants
Healthy Participants
Participants who enroll into a cohort that requires lumbar puncture
Participants with Alzheimer's disease
Exclusion Criteria:
Any participants
Participants with Alzheimer's disease
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New Orleans Center for Clinical Research | Knoxville | Tennessee | 37920 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39513754 | Derived | Schauer SP, Toth B, Lee J, Honigberg LA, Ramakrishnan V, Jiang J, Kollmorgen G, Bayfield A, Wild N, Hoffman J, Ceniceros R, Dolton M, Bohorquez SMS, Hoogenraad CC, Wildsmith KR, Teng E, Monteiro C, Anania V, Yeh FL. Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology. Alzheimers Dement. 2024 Dec;20(12):8855-8866. doi: 10.1002/alz.14346. Epub 2024 Nov 8. |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| RO7105705 | Drug | Participants will receive single or multiple doses of RO7105705 IV or SC. |
|
| Serum Concentration of RO7105705 - Single Dose Cohorts: IV Administration | Pre-dose, end of infusion (60-90 minutes), Hour 4, 8, 12 on Day 1, Days 2, 3, 8, 15, 29, 43, 57, 85, 113 |
| Serum Concentration of RO7105705 - Single Dose Cohorts: SC Administration | Pre-dose, Hour 4, 8, 12 on Day 1, Days 2, 3, 4, 6, 8, 15, 29, 43, 57, 85, 113 |
| Serum Concentration of RO7105705 - Multiple Dose Cohorts: IV Administration | Pre-dose, end of infusion (60-90 minutes), Hour 4, 8, 12 on Days 1, 8 15, 22, Days 2, 3, 23, 29, 36, 50, 64, 78, 106, 134 |
| Change From Baseline to Week 19 in Cognitive Function as Assessed Using the Mini-Mental State Examination (MMSE) in Alzheimer's Disease Participants | Baseline, Week 19 |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |