Clinical Trials

BMS-986446 for Early Alzheimer’s Disease.

BMS-986446 is a monoclonal antibody directed against extracellular tau protein, thereby slowing the toxic spread of this protein in Alzheimer’s disease. This phase 2 study will evaluate the safety, tolerability, and efficacy of BMS-986446 in participants ages 50-80 years with early Alzheimer’s disease for 76 weeks. Participants will be randomly assigned in a 4:3:3 ratio to receive either 1400 mg or 4200 mg of BMS-986446 or placebo (70% probability of receiving active BMS-986446). Infusions will occur every 4 weeks. All participants will receive 5 MRI scans and will also undergo 3 tau PET scans. Participants who complete the double-blind treatment phase may be eligible to enter a 96-week open-label extension study in which all subjects will receive BMS-986446. Permits concurrent treatment with cholinesterase inhibitors and/or memantine, providing they have been on a stable dose for at least 12 weeks prior to baseline. HIC# 2000037714.

CT1812 for Early Alzheimer’s Disease

CT1812 is a sigma-2 receptor modulator that is thought to displace and reduce binding of toxic beta-amyloid oligomers to neuronal synapses, with the potential to provide clinical benefit in Alzheimer’s disease. This is a Phase 2, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of CT1812 in participants aged 50 to 85 with early Alzheimer’s disease. Participants will be randomly assigned in a 1:1:1 ratio to receive either 100mg or 200mg of CT1812 or placebo daily for 18 months (67% chance of receiving active study drug). All participants will receive 3 MRI scans and will also undergo either an amyloid PET scan or a lumbar puncture to confirm the presence of cerebral Aβ accumulation. Participants will have the option of participating in amyloid PET and/or cerebrospinal fluid (CSF) lumbar puncture substudies. Permits concurrent treatment with cholinesterase inhibitors and memantine. HIC# 2000035336.

BAN2401 for Individuals at Risk for Alzheimer’s Dementia (AHEAD, A3-45 Study)

A stage of “preclinical Alzheimer’s disease” has recently been defined based on biomarker evidence of amyloid-β pathology before the stage of clinical symptoms. Clinically “normal” older individuals with elevated Aβ pathology (by PET scan) are at increased risk for cognitive decline and progression to Alzheimer’s dementia. BAN2401 is a humanized monoclonal antibody with high selectivity for soluble amyloid-β protofibrils. This is a 4-year, double-blind, placebo-controlled, phase 3 study to evaluate the safety, tolerability, and efficacy of BAN2401 in cognitively normal participants ages 55-80 years who are at risk of developing Alzheimer’s dementia. Participants with intermediate (A3 study) or elevated (A45 study) levels of brain amyloid on a screening PET scan will be randomized to receive intravenous BAN2401 or placebo (50% probability of receiving active BAN2401). A3 study participants will receive BAN2401 (titrated up to 10mg/kg) or placebo every four weeks. A45 study participants will receive BAN2401 (titrated up to 10mg/kg) or placebo every 2 weeks for the first 96 weeks, then every four weeks for the remainder of the study. Participants will be required to have at least 12 MRI scans, three amyloid (18F-NAV4694) PET scans, and three tau (18F-MK6240) PET scans. Participants can also participate in an optional lumbar puncture substudy. Does NOT permit concurrent treatment with cholinesterase inhibitors and memantine. HIC# 2000027712.

BAN2401 for Prodromal or Mild Alzheimer’s Disease

BAN2401 is a humanized monoclonal antibody with high selectivity for soluble amyloid-β protofibrils. This is a Phase 3, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of BAN2401 in participants ages 50-90 years with early (prodromal or mild) Alzheimer’s disease. Participants will be randomized to receive BAN2401 (10 mg/kg) or placebo that will be administered intravenously (50% probability of receiving active BAN2401). Participants will have up to 7 brain MRI scans and up to 2 18F-florbetaben PET scans or 1 lumbar puncture. Additionally, participants will have the option of participating in 7 additional PET scans (4 18F-florbetaben and 3 18F-MK-6240) and 2 additional lumbar punctures provided with study participation. Finally, participants who complete the double-blind phase will have the option of participating in a 2-year study extension in which all participants will receive BAN2401. Permits concurrent treatment with cholinesterase inhibitors and/or memantine, providing they have been on a stable dose at least 4 weeks prior to screening. (MMSE ≥22). HIC# 2000026162.

Donanemab for Prodromal or Mild Alzheimer’s Disease

Donanemab is an antibody directed at the pyroglutamate modification of the third amino acid of amyloid beta (N3pG Aβ) epitope that is present only in brain amyloid plaques. This is a Phase 2, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of donanemab in participants ages 60-85 years with prodromal or mild Alzheimer’s disease. Participants will be randomized to receive donanemab (1400 mg) or placebo that will be administered intravenously (50% probability of receiving active donanemab). Participants will have up to five brain MRI scans, up to four 18F-florbetapir PET scans, and two 18F-flortaucipir PET scans. Permits concurrent treatment with cholinesterase inhibitors and/or memantine, providing they have been on a stable dose at least 4 weeks prior to baseline. (MMSE ≥20). HIC# 2000028807

JNJ-63733657 for Prodromal or Mild Alzheimer’s Disease

JNJ-63733657 is a monoclonal antibody directed against extracellular tau protein, thereby slowing the toxic spread of this protein in Alzheimer’s disease. This phase 2 study will evaluate the safety, tolerability, and efficacy of JNJ-63733657 in participants ages 55-80 years with prodromal or mild Alzheimer’s disease for 128 weeks. Participants will be randomized to receive study drug (1000 mg or 3000 mg) or placebo that will be administered intravenously (67% probability of receiving active JNJ-63733657). Infusions will occur every 4 weeks. Participants will have up to 6 brain MRI scans, up to 3 Tau PET scans, and up to 3 optional lumbar punctures with study participation. After completing the double-blind study, participants may have the option of continuing in a long-term extension study in which all subjects will receive JNJ-63733657. Permits concurrent treatment with cholinesterase inhibitors and/or memantine, providing they have been on it for at least 4 months and on a stable dose at least 2 months prior to screening. HIC# 2000029685.

Bepranemab for Prodromal or Mild Alzheimer’s Disease

Bepranemab (UCB0107) is a monoclonal antibody targeting the mid-domain of the tau peptide that is being developed to block and reduce the cell-to-cell spread of tau pathology. This is a Phase 2, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of bepranemab in individuals with prodromal or mild Alzheimer’s disease. Participants will be randomly assigned in a 1:1:1 ratio to receive bepranemab at one of two active doses or placebo, administered intravenously every 4 weeks for up to 80 weeks (67% chance of receiving active study drug). All participants will undergo either a 18F-Florbetapir PET scan or a lumbar puncture (as part of an optional CSF substudy) to confirm the presence of cerebral Aβ accumulation. All participants will also receive 4 MRI scans and 3 18F-GTP1 tau PET scans. Participants will have the option of continuing in an open-label extension period after completion of the double-blind treatment period. Permits concurrent treatment with cholinesterase inhibitors and memantine. HIC# 2000031213

Longitudinal PET Imaging of Biomarkers in Alzheimer’s Disease

Since synaptic loss is a robust and consistent component of Alzheimer’s disease (AD) pathology, direct measurement of synaptic density could be an important step for understanding disease progression and monitoring therapeutic interventions. We recently developed 11C UCB-J, a PET tracer for quantitative measurement of a vesicle membrane protein present in virtually all synapses. The purpose of this research is to examine these synapses, as measured using Positron Emission Tomography (PET) scanning and the tracer 11C UCB-J, and to integrate this information with other biomarkers of disease, including Aβ and tau deposition. Participants will include individuals between the ages of 50 and 85 with mild cognitive impairment (MCI) or dementia due to AD, as well as participants without cognitive impairment. Additionally, the sample will include participants aged 40 to 75 years with and without a first-degree family history of AD. The study procedures include medical history and physical exam, blood and urine samples, memory testing, an MRI scan, and up to 4 PET scans every two years over the course of 10 years. Length of participation is approximately 10 years. HIC#2000024532.

PET Imaging of Synaptic Density in Alzheimer’s Disease

Since synaptic loss is a robust and consistent component of Alzheimer’s disease (AD) pathology, direct measurement of synaptic density could be an important step for understanding disease progression. We recently developed [11C]APP311, a PET tracer for quantitative measurement of a vesicle membrane protein present in virtually all synapses. The purpose of this research is to examine these synapses, as measured using Positron Emission Tomography (PET) scanning and the tracer [11C]APP311, in participants between the ages of 55 and 90 with mild cognitive impairment (MCI) or dementia due to AD, as well as participants without cognitive impairment. The study procedures include medical history and physical exam, blood and urine samples, memory testing, an MRI scan, and up to 3 PET scans. Length of participation is approximately 6 months. Participants will be compensated up to $800 for their time. HIC#1608018300

Alzheimer’s Disease Neuroimaging Initiative 4 (ADNI 4).

At present, the development of drugs for patients with Alzheimer’s disease is costly and time consuming. The validation of suitable biomarkers that track the progression of the disease and reflect underlying pathology is critical to streamlining this process. This is a multi-center observational research study designed to look at the relationships between clinical, cognitive, imaging, genetic, and biomarker tests in order to understand the full spectrum of Alzheimer’s disease (AD) from its earliest stage. It will enroll about 1500 participants ages 55 – 90 (inclusive) across three cohorts: cognitively normal, mild cognitive impairment, and mild AD dementia. Approximately 750 of those participants will have also been in the ADNI-3 study. At least 50-60% of newly enrolled participants will come from populations that have been underrepresented in earlier iterations of ADNI (e.g., Black, Latinx, and persons with less than 12 years of education) to enhance the generalizability of results. Study participation will last for about 4-5 years based on cohort (up to 6 visits total). All subjects will undergo MRI scans and up to 8 PET scans and can participate in optional lumbar puncture procedures (up to 3 lumbar punctures). They will also have the option to participate in a brain donation program. HIC#2000034800.

Apolipoprotein E and Other Genetic Factors in Alzheimer’s Disease

Apolipoprotein E (ApoE) is the major genetic risk factor for AD. The purpose of this research is to determine whether ApoE is related to differences among patients with AD, for example in the rate of progression, associated symptoms, and brain imaging features. We may also study other genes thought to be related to AD or brain function. Subjects participating in other studies in the ADRU may also participate in this study by providing a blood sample for genetic testing. HIC# 0505008171

Alzheimer’s Disease Research Center (ADRC) – Clinical Core

The goal of the Clinical Core of the Yale ADRC is to perform research diagnostic evaluations for a large clinical population and to follow participants longitudinally to provide data for a broad range of studies related to Alzheimer’s disease and other dementias. This research will also focus on biomarkers and their utility in the earliest stages of disease. The Clinical Core will evaluate and enroll approximately 100 participants annually from the following categories: cognitively normal individuals—both with and without a first-degree family history of Alzheimer’s disease, individuals with Mild Cognitive Impairment, individuals with mild-moderate Alzheimer’s dementia, individuals with other neurodegenerative dementias. Participants will have an initial evaluation, including cognitive tests, blood samples, and a physical and neurological examination. Participants will be asked to return for annual follow-up visits in which these assessments will be repeated. Subjects will also have the option to participate in substudies involving lumbar puncture, MRI scans, and brain autopsy. HIC#1505015818