Protocol H8A-MC-LZAZ (a) / ADC-040-A4
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)
Alzheimers disease (AD) is an age-related neurodegenerative disorder characterized by progressive decline in cognitive function and ability to perform activities of daily living,and ultimately can lead to death due to complications of the disease. Pathologic hallmarks of AD identified at autopsy include the presence of neuritic amyloid-B (AB) plaques. The AB plaques are protein deposits that accumulate outside and around neurons. The AB hypothesis for AD, which states that the production and deposition of AB (later forming neuritic AB plaques) is an early and necessary event in the pathogenesis of AD, suggests that treatments that slow the synthesis or deposition of AB, or that increase clearance, might be expected to slow the progression of AD. One such treatment is immunotherapy. Solanezumab is a monoclonal antibody that is being developed as a passive immunization therapy to reduce AB burden. Converging evidence from both genetic at risk and age at risk cohorts suggests that the pathophysiological process of AD begins well more than a decade before the clinical stage now recognized as AD dementia, and that neurodegenerationis already apparent by the stage of Mild Cognitive Impairment (MCI) / prodromal AD. The A4 study will target those participants with evidence of brain amyloid pathology on PET amyloid imaging who are still clinically normal but at high risk for cognitive decline (defined as preclinical AD).Objectives: The primary objective of this study is to test the hypothesis that solanezumab, administered as an intravenous infusion at a dose of 400 mg every 4 weeks for 3 years, will slow the cognitive decline with placebo in participants with preclinical AD. Study Design: This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing 400-mg solanezumab with placebo given as infusions once every 4 weeks 3 years in approximately 1150 outpatients with preclinical AD. Diagnosis and Main Criteria for Inclusion and Exclusions: Participants will be males and females 65 to 85 years old with preclinical AD. The study population is defined as participants with preclinical AD who have an MMSE score between 25 and 30, a Logical Memory test, part IIa score between 6 and 18, and a global CDR of 0; and having screening florabetapir PET scan indicating brain amyloid pathology.Efficacy: Preclinical Alzheimer Cognitive Composite (ADCS-PACC)Primary Analysis: The primary endpoint ADCS-PACC will be analyzed using an MMRM analysis.
Amyloid Imaging in Vascular Cognitive Impairment
Florbetapir F 18 is a radioactive drug approved in April, 2012, by the Food and Drug Administration (FDA) that may allow doctors to image changes in the brain using a PET (Positron Emission Tomography) scan machine. The purpose of this study is to further evaluate the safety and imaging characteristics of florbetapir F 18, especially in normal aging and in persons with vascular risk factors.Florbetapir F 18 binds to amyloid- peptide that accumulates in the brain with aging and in Alzheimer disease. These accumulations are called amyloid plaques. Florbetapir F 18 binds to amyloid plaques in the brain and emits a low level of gamma rays which can be detected by a PET camera. In this research study, up to 42 subjects, will be enrolled in order to evaluate the safety and imaging characteristics of florbetapir F 18 and to clarify if there is a relationship between vascular risk factors and amyloid- peptide. Participant will be older than age 70 years and will be recruited into 6 groups: cognitive normal (n=9) versus cognitively impaired (n=33). Each group will be further stratified by vascular risk (low, medium, high) based on the Framingham Cardiovascular Risk Factor Profile obtained in the Aging Brain Research Study (HS18-00114).Imaging results will be qualitative, semiquantitative, and quantitative. Qualitative assessment of image (A+ or A-); semiquantitative rating (0-4); Quantitative assessment (SUVR) will be measured in the following brain regions: Frontal cortex, temporal cortex, parietal cortex, posterior cingulate cortex, anterior cingulate, andprecuneus, Global average of all of the aboveAll values will be summarized by diagnostic groups. Frequency distributions including counts and percents will be included for all categorical outcomes. Summary statistics including mean, standard deviation, median, minimum and maximumvalues will be presented for all continuous outcomes. Associations will be sought between vascular risk (low, medium, high) and Florbetapir uptake (positive versus negative).
Recruiting | Intracerebral Hemorrhage | Not Multisite
Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase I
Rationale: The first clinical trial to evaluate the safety and tolerability of allopregnanolone (Allo), a naturally occurring brain steroid, in mild cognitive impairment and Alzheimers disease participants. Allo is an investigational drug molecule shown in animal studies to stimulate the birth of new neurons, rescue cognition and lower indicators of Alzheimers disease. Objectives: 1) The first group of participants in the trial will be given one dose of Allo once per week for 12 weeks, only increasing the dose for the next group of participants when the lower dose has been shown to be safe. The primary goal is to determine the highest dose that is safe and tolerated by participants. 2) Analysis will also be done on blood samples taken from participants at the beginning and end of the trial to determine how the body responds to the drug molecule. 3) As per FDA requirements, the trial will investigate potential safety concerns including blood vessel changes via brain imaging. Secondary goals are to assess the short-term effects of Allo treatment on learning and memory as well as detect changes via MRI brain imaging to help researchers prepare for a larger-scale clinical trial. Study Population: The trial will enroll 24 participants (12 post-menopausal women, 12 men) diagnosed with mild cognitive impairment (MCI) or early Alzheimers disease. Participants must be 55 years of age or older, have a score on the Mini-Mental State Examination greater than 20, and be able to provide informed consent. Study Methodology: Participants will be given Allo or placebo intravenously once per week for 12 weeks. Description of Study Arms: Each dose (low to high) will have a separate, gender balanced group of 8 participants. 6 participants will be given Allo and 2 will be given placebo. At the end of the study, 18 participants will have received Allo and 6 will have received placebo. Endpoints: To determine the safety and tolerability of Allo, the trial will evaluate 1) if any, how much sedation after each dose of Allo; 2) if any, how many side-effects participants report; 3) any clinically significant changes in participants (for example: blood tests, weight, heart rate, heart monitor, brain scan, tests of memory) and 4) changes in brain imaging.