A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Intravenous and Subcutaneous RO7105705 Administered in Healthy Volunteers and Patients With Mild-to-Moderate Alzheimer's Disease
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Alzheimer's Disease
- Sponsor
- Genentech, Inc.
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Change from Baseline in Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All participants
- •Total body weight between 45 and 120 kilogram (kg), inclusive
- •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
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), laboratory tests, and vital signs
- •Clinical laboratory evaluations (including chemistry panel fasted \[fasted at least 8 hours\], complete blood count (CBC), and urine analysis) within the reference range for the test laboratory, unless deemed not clinically significant by the investigator
- •Negative test for selected drugs of abuse at screening and at check-in
- •Agreement to use highly effective contraception measures
- •Healthy Participants
- •Ages 18-80 years inclusive
- •No history of symptomatic cognitive decline and no concern about clinically significant cognitive impairment by the participant or by the investigator
Exclusion Criteria
- •Any participants
- •Pregnant or lactating, or intending to become pregnant within 16 weeks after last dose of study drug
- •Participation in a clinical trial within 30 days before randomization; use of any experimental oral therapy within 30 days or 5 half-lives prior to Day 1, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to Day 1, whichever is greater
- •Any non-experimental vaccine within 2 weeks of randomization, until 2 weeks after the last dose
- •Surgery or hospitalization during the 4 weeks prior to screening
- •Planned procedure or surgery during the study
- •Blood transfusion within 8 weeks prior to screening
- •Donation or loss of blood (excluding the volume of blood that will be drawn during screening procedures) as follows: 50-499 milliliters (mL) of blood within 30 days or greater than (\>) 499 mL of blood within 56 days prior to study drug administration
- •Poor peripheral venous access
- •Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody
Arms & Interventions
Multiple Dose Placebo IV
Healthy participants or participants with Alzheimer's disease will receive multiple doses of matching placebo IV QW, a total of 4 doses.
Intervention: Placebo
Multiple Dose RO7105705 IV
Healthy participants or participants with Alzheimer's disease will receive multiple doses of RO7105705 IV QW, a total of 4 doses.
Intervention: RO7105705
Single Dose RO7105705 SC
Healthy participants will receive a single dose of RO7105705 SC on Day 1.
Intervention: RO7105705
Single dose Placebo IV
Healthy participants will receive a single dose of placebo IV on Day 1.
Intervention: Placebo
Single dose RO7105705 IV
Healthy participants will receive a single dose of RO7105705 IV on Day 1.
Intervention: RO7105705
Outcomes
Primary Outcomes
Change from Baseline in Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score
Time Frame: Baseline, up to approximately 134 days
Number of Participants with Adverse Events
Time Frame: Screening up to Day 134
Number of Participants with Dose Limiting Adverse Events (DLAEs)
Time Frame: Day 1 up to Day 36
Secondary Outcomes
- 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)
- 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)
- 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)