Clinical trial NCT02820896: A Study of RO7105705 in Healthy Participants and Participants With Mild-to-Moderate Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-01
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

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
* Availability of a person (caregiver) who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits, which require partner input for scale completion, and signs the necessary consent form
* Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing
* Clinical diagnosis of probable Alzheimer's disease dementia based on National Institute on Aging-Alzheimer's Association criteria
* Screening mini-mental state examination (MMSE) score of 16-28 points, inclusive
* Screening Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1.0, or 2.0
* Positive florbetapir amyloid positron emission tomography (PET) scan by qualitative read
* If already taking cholinesterase inhibitor and/or memantine therapy for Alzheimer's disease, on a stable dose for at least 4 weeks prior to screening. There should be no intent to, discontinue, or alter the dose of any Alzheimer's disease therapy for the duration of the study

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
* 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
* Any serious medical condition or abnormality in clinical laboratory tests; systemically, clinically immunocompromised because of continuing effects of immune-suppressing medication

Participants with Alzheimer's disease

* History or presence of clinically evident vascular disease potentially affecting the brain
* History or presence of stroke within the previous 2 years or documented history of transient ischemic attack within the previous 12 months
* History or presence of intracranial tumor that is clinically relevant in the opinion of the investigator
* Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
* History or presence of central nervous system (CNS) or systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
* History or presence of a neurologic disease other than Alzheimer's disease that may affect cognition
* Magnetic resonance imaging (MRI) evidence of 1) more than two lacunar infarcts, 2) any territorial infarct less than (\>) 1 centimeters (cm), or 3) significant fluid attenuated inversion recovery (FLAIR) hyperintense lesions in the cerebral white matter that may, in the investigator's opinion, contribute to cognitive dysfunction

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Screening up to Day 134
measure: Number of Participants with Dose Limiting Adverse Events (DLAEs)
timeFrame: Day 1 up to Day 36
measure: Change from Baseline in Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Baseline, up to approximately 134 days
Secondary outcomes:
measure: Change From Baseline to Week 19 in Global Function as Assessed Using the Clinical Dementia Rating (CDR) Global Score in Alzheimer's Disease Participants
timeFrame: Baseline, Week 19
measure: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs)
timeFrame: Baseline, Days 29, 57, 113
measure: Serum Concentration of RO7105705 - Single Dose Cohorts: IV Administration
timeFrame: 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
measure: Serum Concentration of RO7105705 - Single Dose Cohorts: SC Administration
timeFrame: Pre-dose, Hour 4, 8, 12 on Day 1, Days 2, 3, 4, 6, 8, 15, 29, 43, 57, 85, 113
measure: Serum Concentration of RO7105705 - Multiple Dose Cohorts: IV Administration
timeFrame: 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
measure: Change From Baseline to Week 19 in Cognitive Function as Assessed Using the Mini-Mental State Examination (MMSE) in Alzheimer's Disease Participants
timeFrame: Baseline, Week 19
Other outcomes:
Locations:
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: