A Phase Ib, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel-Arm, Multiple-Dose Study to Assess The Safety, Tolerability, And Pharmacokinetics of Intravenous Crenezumab Administered in Patients With Mild to Moderate Alzheimer's Disease
Overview
- Phase
- Phase 1
- Intervention
- Crenezumab dose level 1
- Conditions
- Alzheimer Disease
- Sponsor
- Genentech, Inc.
- Enrollment
- 77
- Locations
- 13
- Primary Endpoint
- Number of participants with amyloid-related imaging abnormalities-hemorrhage (ARIA-H)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination [MMSE] 18 to 28 points, inclusive). An optional open-label extension (OLE) will be offered after the completion of initial double-blind stage.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Body weight greater than or equal (\>/=) 45 kilograms (kg) and less than or equal (\</=) 120 kg
- •Ages 50-90 years, inclusive
- •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
- •Willingness and ability to complete all aspects of the study; the participant should be capable of completing assessments either alone or with the help of the caregiver
- •Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing
- •Clinical diagnosis of probable mild to moderate AD based on the national institute on neurological and communication disease and stroke/Alzheimer's disease and related disorders association (NINCDS/ADRDA) criteria or probable major neurocognitive disorder due to AD of mild to moderate severity based on diagnostic and statistical manual of mental disorders, version 5 (DSM-5) criteria
- •Screening MMSE score of 18-28 points, inclusive
- •Screening clinical dementia rating global score (CDR-GS) of 0.5 or 1.0
- •Screening geriatric depression (GDS)-15 score less than (\<) 6
- •Positive florbetapir amyloid positron emission tomography (PET) scan by qualitative read conducted by the core/central PET laboratory
Exclusion Criteria
- •History or presence of clinically evident vascular disease potentially affecting the brain that, in the opinion of the investigator, has the potential to affect cognitive function
- •History or presence of stroke within the previous 2 years or documented history of transient ischemic attack within the previous 12 months
- •History of severe, clinically significant central nervous system trauma
- •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 systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
- •History or presence of a neurologic disease other than AD that may affect cognition
- •Presence of superficial siderosis, more than four cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage
- •Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication to MRI
- •History or presence of atrial fibrillation except if only one episode that resolved more than 1 year ago and for which treatment is no longer indicated or that in the investigator's judgment poses no risk for future stroke
Arms & Interventions
Double-blind treatment window: Crenezumab dose level 1
Participants will recieve crenezumab dose level 1 once every 4 weeks.
Intervention: Crenezumab dose level 1
Double-blind treatment window: Crenezumab dose level 2
Participants will receive crenezumab dose level 2 once every 4 weeks.
Intervention: Crenezumab dose level 2
Double-blind treatment window: Crenezumab dose level 3
Participants will receive crenezumab dose level 3 once every 4 weeks.
Intervention: Crenezumb dose level 3
Double-blind treatment window: Placebo
Participants will receive placebo matched to crenezumab once every 4 weeks.
Intervention: Placebo
Optional OLE window: Crenezumab
Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks.
Intervention: Crenezumab dose level 1
Optional OLE window: Crenezumab
Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks.
Intervention: Crenezumab dose level 2
Optional OLE window: Crenezumab
Participants will receive crenezumab dose levels 1 2, or 3 once in every 4 weeks.
Intervention: Crenezumb dose level 3
Outcomes
Primary Outcomes
Number of participants with amyloid-related imaging abnormalities-hemorrhage (ARIA-H)
Time Frame: Up to Week 13
Number of participants with of non-serious AEs of special interest
Time Frame: From baseline up to follow-up period (Week 69)
Number of participants with changes from baseline in vital signs, electrocardiogram (ECG) and clinical laboratory results
Time Frame: From baseline up to follow-up period (Week 69)
Number of participants with amyloid-related imaging abnormalities-edema/effusion (ARIA-E)
Time Frame: Up to Week 13
Number of participants with anti-crenezumab antibodies
Time Frame: From baseline up to follow-up period (Week 69)
Number of participants with suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, as determined using the columbia-cuicide severity rating scale (C-SSRS)
Time Frame: From baseline up to follow-up period (Week 69)
Number of participants with adverse events (AEs) and serious adverse events (SAEs) according to national cancer institute common terminology criteria for adverse events, version 4.0 (NCICTCAE v4.0)
Time Frame: From baseline up to follow-up period (Week 69)
Secondary Outcomes
- Serum concentration of crenezumab(Pre-dose on Day 1, 60-90 minutes (min) post infusion on Day 1, Days 2, 8, Week 2, pre-dose and 60-90 min post infusion on dosing day of Weeks 5, 9, 13, and 21; pre-dose and 60-90 min post infusion on dosing day of Weeks 25, 53, 61, and 69)