This Phase II, open-label extension (OLE), multicenter study will evaluate the long-term safety and tolerability of crenezumab in participants with mild to moderate Alzheimer's disease who have participated in and completed the treatment period of the Phase II Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578). Participants who received placebo in Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578) will receive crenezumab. Anticipated time on study treatment is 144 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
360
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
Percentage of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. . An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Up to 50 months
Percentage of Participants by Nature of AEs
A serious adverse event (SAE) is any AE that meets any of the following criteria: fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect in a neonate/infant. Non-SAE of special interest for this study include the following: cerebral vascular edema, Superficial siderosis of central nervous system, cerebral micro-hemorrhages or macro-hemorrhages, pneumonia, liver injury.
Time frame: Up to 50 months
Percentage of Participants by Severity of AEs
AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 was used for assessing adverse event severity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1) mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2) moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3) severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4) life-threatening consequences; urgent intervention indicated, Grade 5) death related to AE.
Time frame: Up to 50 months
Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Banner Alzheimer's Institute
Phoenix, Arizona, United States
Mayo Clinic
Scottsdale, Arizona, United States
Banner Sun Health Research Insitute
Sun City, Arizona, United States
Pharmacology Research Inst
Encino, California, United States
Margolin Brain Institute
Fresno, California, United States
Univ of CA San Diego; Neurosciences Comp.Alzheimer's
La Jolla, California, United States
USC School of Medicine
Los Angeles, California, United States
University of California Los Angeles (UCLA)
Los Angeles, California, United States
Pharmacology Research Inst
Newport Beach, California, United States
Pacific Neuroscience Med Grp
Oxnard, California, United States
...and 76 more locations
ATA is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. Percentage of participants at post-baseline with positive results for ATA against crenezumab are reported.
Time frame: Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)
Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E)
Alzheimer's disease (AD) is associated with ARIA. The occurrence of imaging abnormalities believed to represent cerebral vasogenic edema, has been reported in association with the investigational use of compounds that are intended to treat Alzheimer's disease by reducing Abeta in the brain. Here, the percentage of participants with symptomatic and asymptomatic ARIA-E were reported.
Time frame: Baseline, Weeks 23, 47, 71, 97, 121 and 153
Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H)
AD is associated with ARIA. Cerebral micro-hemorrhages (microbleeds \[MBs\]) are radiologically defined as small dot-like foci of signal loss observed on magnetic resonance imaging (MRI) sequences sensitive for paramagnetic tissue properties. The occurrence of MBs has also been identified as an adverse event in anti-amyloid vaccination trials, and together with superficial siderosis, they have been termed ARIA-H.
Time frame: Baseline, Weeks 23, 47, 71, 97, 121 and 153