A Study of RO7105705 in Healthy Participants and Participants With Mild-to-Moderate Alzheimer's Disease

NCT02820896 | Completed Phase 1

• 1 other identifier: GN39058
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (6)

• 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: 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

Study Arms (5)

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.

Drug: Placebo

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.

Drug: RO7105705

Single Dose RO7105705 SC

EXPERIMENTAL

Healthy participants will receive a single dose of RO7105705 SC on Day 1.

Drug: RO7105705

Single dose Placebo IV

PLACEBO COMPARATOR

Healthy participants will receive a single dose of placebo IV on Day 1.

Drug: Placebo

Single dose RO7105705 IV

EXPERIMENTAL

Healthy participants will receive a single dose of RO7105705 IV on Day 1.

Drug: RO7105705

Interventions

Placebo DRUG

Participants will receive single or multiple doses of RO7105705 matching placebo IV.

Multiple Dose Placebo IV; Single dose Placebo IV

RO7105705 DRUG

Participants will receive single or multiple doses of RO7105705 IV or SC.

Multiple Dose RO7105705 IV; Single Dose RO7105705 SC; Single dose RO7105705 IV

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Participants who enroll into a cohort that requires lumbar puncture
• No contraindication to lumbar dural puncture, including coagulopathy, concomitant anticoagulation, thrombocytopenia, prior lumbar spinal surgery, or other factor that precludes safe lumbar puncture in the opinion of the investigator
• Participants with Alzheimer's disease
• Ages 50-80 years, inclusive
• The participant should be capable of completing assessments either alone or with the help of the caregiver

You may not qualify if:

• 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
• Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Administration of any herbal or nutritional supplements (with the exception of standard vitamins and calcium supplements) within 7 days prior to study dose
• Past history of seizures, prior traumatic brain injury, schizophrenia, schizoaffective disorder, or bipolar disorder
• At risk of suicide in the opinion of the investigator
• Serious infection requiring oral and IV antibiotics within 30 days prior to screening

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• 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.

  PMID: 39513754 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 1, 2016
• Study Start: June 29, 2016
• Primary Completion: June 26, 2017
• Study Completion: June 26, 2017
• Last Updated: July 21, 2017

Record last verified: 2017-07

Locations

US (1)