Industry Sponsored Pharma Trials

 1.       A4 Study: Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss (A4)

 Description: The A4 study is a clinical trial for older individuals who have evidence of amyloid plaque build-up in their brains who may be at risk for memory loss and cognitive decline due to Alzheimer's disease. The A4 study will test an anti-amyloid investigational drug in older individuals who do not yet show symptoms of Alzheimer's disease cognitive impairment or dementia with the aim of slowing memory and cognitive decline. The A4 study will also test whether anti-amyloid treatment can delay the progression of AD related brain injury on imaging and other biomarkers.

Sponsor/Funder: Eli Lilly & Company

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT02008357

2.       Graduate: A Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants With Alzheimer's Disease (AD)

Description: This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 116. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.

Study Sponsor/Funder: Hoffmann-La Roche

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT04374253

3.       Post-Graduate: A Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants with Alzheimer's Disease (AD)

Description: This is an open-label, multicenter, rollover study to evaluate the safety, tolerability, and efficacy of long-term administration of open-label gantenerumab in participants with AD who completed Study WN29922 or WN39658, either the double-blind or open-label extension (OLE) part. Participants who were in the active arm in the double blind part and those who have completed OLE part in the parent study, will continue receive open-label gantenerumab 510 mg sub-cutaneously (SC) every 2 weeks (Q2W). Participants who are naive to gantenerumab treatment will be required to undergo the 3 step up titration scheme as in the parent study before receiving target dose of open label gantenerumab.

Study Sponsor/Funder: Hofmann-La Roche

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT04374253

4.       Trailblazer: A Study of Donanemab (LY3002813) in Participants with Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)

Description: TRAILBLAZER-ALZ 2 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of N3pG antibody (donanemab) in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) with the presence of brain tau pathology. Following the double-blind 76-week main study period, a double-blind 78-week long-term extension period is added to further evaluate donanemab efficacy and safety over time. Participants from the addendum safety cohort are not eligible for the extension period.

Study Sponsor/Funder: Eli Lilly & Company

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT04437511

5.       Icon/UCB: A Study to Test the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Patients with Mild Cognitive Impairment or Mild Alzheimer's Disease (AD)

Description: The purpose of the study is to investigate the effect of bepranemab versus (vs) placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) up to Week 80 in study participants with prodromal or mild Alzheimer's disease (AD). Upon completion of the 80-week Double-blind Treatment Period, study participants will be eligible to enter a 48-week Open-label Extension Period with planned treatments of bepranemab for 44 weeks, followed by a Safety Follow-up Visit 20 weeks after the last infusion of investigational medicinal product.

Study Sponsor/Funder: UCB Biopharma SRL

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT04867616

6.       Evoke & Evoke plus: A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease

Description: This study is done to find out whether the medicine, semaglutide, has a positive effect on early Alzheimer's disease. Participants will either get semaglutide or placebo (a "dummy" medicine which does not contain any study medicine) - which treatment participants get is decided by an equal chance. The study will last for up to 173 weeks (about 3 years and 4 months). Participants will have 17 clinic visits and 1 phone call with the study doctor. The study includes various tests and scans. At 10 of the clinic visits participants will have blood samples taken. Participants must have a study partner, who is willing to take part in the study. Women cannot take part if pregnant, breastfeeding or plan to become pregnant during the study period. A cerebrospinal fluid (CSF) sub-study will be performed as a part of the study. The sub-study will be performed on a selection of sites based on their experience with CSF sampling and willingness to participate in this sub-study. The endpoints related to this sub-study are exploratory only.

Study Sponsor/Funder: Novo Nordisk

ClinicalTrials.gov links:

https://clinicaltrials.gov/ct2/show/NCT04777396

https://clinicaltrials.gov/ct2/show/results/NCT04777409

7.       AHEAD: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid

Description: The primary purpose of this study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial).

Study Sponsor/Funder: Eisai Inc.

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT04468659

8.       EMBARK: A Study to Evaluate Safety and Tolerability of Aducanumab in Participants With Alzheimer's Disease Who Had Previously Participated in the Aducanumab Studies 221AD103, 221AD301, 221AD302 and 221AD205

Description: The primary objective is to evaluate the safety and tolerability of aducanumab over 100 weeks of treatment after a wash-out period imposed by discontinuation of feeder studies in participants who had previously received aducanumab (i.e. previously treated participants) or who had previously received placebo (i.e. treatment-naïve participants).

Study Sponsor/Funder: Biogen

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT04241068

9.       Envision: A Study to Verify the Clinical Benefit of Aducanumab in Participants with Early Alzheimer's Disease (ENVISION)

Description:  The purpose of this Phase 3b/4 confirmatory study is to verify the clinical benefit of aducanumab compared with placebo in participants with Alzheimer’s disease, including those with MCI due to Alzheimer’s disease or mild Alzheimer’s disease dementia. Participants will be assigned to 1 of 2 treatment groups in a 2:1 ratio of aducanumab or placebo administered IV Q4W, respectively. Treatment is initiated via titration, which has been demonstrated to result in a lower incidence of ARIA. Titration will start at 1 mg/kg and will escalate to 3, 6 and 10 mg/kg

Study Sponsor/Funder: Biogen

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT05310071

10.    LAKD: A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1)

Description: TRAILRUNNER-ALZ 1 is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of remternetug in participants with early symptomatic AD. Participants will receive remternetug or placebo administered via subcutaneous injection or intravenous infusion.

Following the 52-week main study period, participants will continue participation for up to an additional 52 weeks in an extension period. Participants who previously received remternetug will receive placebo and participants who previously received placebo will receive remternetug. Thus, all participants will receive remternetug if they complete the study.

An additional 600 participants with early Alzheimer's disease will be enrolled to an addendum safety cohort. The participants will be administered open label remternetug via intravenous infusion. Participants from the addendum safety cohort are not eligible for the extension period.

Study Sponsor/Funder: Eli Lilly

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT05463731

11.    MK-1942-008: Efficacy and Safety of MK-1942 as an Adjunct Therapy in Participants with Mild to Moderate Alzheimer's Disease Dementia (MK-1942-008)

Description: This is a randomized, placebo-controlled, parallel-group, multisite, double-blind study of MK-1942 as adjunctive therapy in participants with mild to moderate AD dementia. The study population will consist of male and female participants aged 55 to 90 years with mild to moderate AD dementia according to clinical criteria (NINCDS-ADRDA) [McKhann, G.,et al 1984]. Participants will continue taking their stable background AD therapy during the study. Approximately 408 participants will be randomized in a 1:1:1 ratio to treatment with either (1) MK-1942 5 mg bid, (2) MK-1942 15 mg bid, or (3) placebo bid, respectively (Section 1.2). MK-1942 or matching placebo will be administered as oral capsules, all of which are the same image. No more than ~ 60% of participants are to be enrolled in each of 2 MMSE strata (MMSE ≤16, ≥17).

Study Sponsor/Funder: Merck Sharp & Dohme LLC

ClinicalTrials.gov link: https://www.clinicaltrials.gov/ct2/show/NCT05602727

Non-Pharma Studies

1.       CCNA-COMPASS ND: The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) Study

Description: COMPASS-ND is Canada’s largest dementia study that aims to better understand various cognitive conditions in the aging population. For the first time, this study will integrate a wide range of measures (e.g. clinical, neuropsychological, imaging data) to address the causes, diagnosis, management, treatment, and prevention of these conditions.

Study Type: Observational, cross-sectional and longitudinal in nature; Study Sponsor-CCNA

Study Link: https://ccna-ccnv.ca/compass-nd-study/

2.       SARTAN: Telmisartan vs. Perindopril in Mild-Moderate Alzheimer's Disease Patients

Description: The SARTAN-AD study is comparing the effects of two approved medications for high blood pressure – Telmisartan and Perindopril – on their ability to maintain brain function in people with mild to moderate Alzheimer’s disease.

Study Type: Health Canada Regulated, longitudinal in nature; Study Sponsor-Sunnybrook Research Institute

ClinicalTrials.gov link: https://clinicaltrials.gov/ct2/show/NCT02085265

3.       ADHD: Adult ADHD: Risk factor for dementia or phenotypic mimic?

Description: Attention-deficit hyperactivity disorder (ADHD) and mild cognitive impairment (MCI) often present with similar cognitive complaints, such as difficulties with controlling attention and impulses. As a result, many older adults with ADHD can be misdiagnosed as having MCI rather than ADHD. This study will compare participants with MCI and ADHD to help improve our ability to distinguish between the two conditions in older adults. The study has 4-hour visits once a year over 3 years.

Study Type: Observational; Study sponsor- Sunnybrook Research Institute

4.       Novel Biomarkers: Novel Biomarkers for Dementia: Arterial stiffness, Cerebrovascular reactivity, Retinal vessels, Gait, Microbiome, Functional Reserve, and Sleep Assessment

Description: This research is to look at new ways of detecting disease. We want to compare new methods (eye assessment, CVR mapping, gut microbiome, gait and balance, and tonometry) with other methods regularly used (cognitive testing and MRI exams). In additions, there is a questionnaire to measure the functional reserve and a sleep assessment using wearable technology.

5.       OPTINA: Validating the Potential of Retinal Imaging with the Optina 4CTM Mydriatic Hyperspectral Retinal Camera to Screen for the Presence and Absence of Amyloid on Brain PET Imaging or Cerebrospinal Fluid Analysis in Aging and the Common Dementias

Description: The study’s objective is to test whether a new camera (MHRC) can detect a protein amyloid-beta (Aß) in the eye in older individuals or those with problems in memory or thinking that may be related to a neurodegenerative condition such as Alzheimer’s, Parkinson’s, or cerebrovascular diseases. 

Study Type: Health Canada Regulated, device trial, observational - Sponsor: OPTINA Diagnostics Inc.

6.       Telomere: A Prospective Cross-sectional, Quantitative 3D Telomeric Imaging Study of Buccal Cells in Mild Alzheimer’s Disease Patients

Description:  The purpose of this study is to determine whether properties of telomeres obtained from cheek cells can be used as a way to detect and diagnose Alzheimer’s disease (AD) in human subjects. Alzheimer’s disease often develops over many years and effective disease management requires early intervention.  A piece of the detection puzzle may lie in the study of biomarkers such as telomeres. Each human cell contains a bundle of DNA called a chromosome, which has a small tail at the end called a “telomere”.  Telomeres are known to become shorter with aging and also to aggregate (cluster) in particular ways, and have other unique characteristics in various diseases.  There is preliminary evidence supporting marked differences in telomere length and characteristics in patients with AD, but some telomere features have not been investigated in the mild stage of AD.  The purpose of this study is to further investigate the telomere patterns in cell samples from the mouth obtained from buccal or cheek swabs, from cognitively normal older adults and from patients with mild AD.

Study Type: Observational – Funder- University of Manitoba

7.       TRIC VCI: Trial of Remote Ischemic pre-Conditioning in Vascular Cognitive Impairment (TRIC-VCI)

Description: The purpose of this study is to determine whether RIC performed once a day on one arm or twice a day on one arm can be implemented successfully by patients, and whether it will improve cognition, brain imaging and blood markers. Remote ischemic conditioning (RIC) is a technique to increase blood flow to the brain. It is intended to be performed daily by patients at home. Each session consists of inflating a blood-pressure cuff around an arm to a pressure sufficient to reduce blood flow to the arm for 5 minutes after which it is kept deflated for 5 minutes to restore normal blood flow. This is repeated four times in each treatment. Inducing this brief period of cut off of blood flow (“ischemia”) in an organ (the arm) that is far away (“remote”) from the brain, may “condition” the brain to increase blood flow and make the brain less vulnerable to problems like new little strokes. There are no treatments for mild vascular cognitive impairment that are approved by Health Canada. This is the first step in a program intended to see if RIC will be an effective treatment for mild vascular cognitive impairment. Thousands of patients have undergone RIC as part of other research studies, and no major harmful effects have been reported.

Study Type: Health Canada Regulated, device trial – Study sponsor- University of Calgary

8.       Alkahest: Blood Samples to Assay Leukotriene B4 Plasma Levels

Description:  The purpose of this study is to collect approximately 10 mL (about 2 teaspoons) of fresh blood from participants. The blood collected in this trial will be analyzed in laboratory research studies to learn more about the levels of specific proteins in the blood. These proteins, called leukotriene B4 (LTB4) and leukotriene A4 hydrolase (LTBA4H), are linked to inflammation and are found in higher levels in older patients. From this study, Alkahest is trying to better understand how these proteins may be related to patients who have been diagnosed with CADASIL and/or other diseases. Learning more about these proteins may help guide future clinical trials in patients with CADASIL or other patient population(s).

Study Type: Observational – Study sponsor-Alkahest Inc.

9.       ADNI 3: Alzheimer’s Disease Neuroimaging Initiative 3

Description:  The ADNI study is an observational research study designed look at the relationship between clinical, cognitive, imaging, genetic and biomarker tests over time, in order to understand the full spectrum of Alzheimer’s disease (AD) from its earliest stages.  The data from this research study will be used in the development of future research studies that will focus on the treatment of AD.  ADNI 4 will be launching soon.

Study Type: Observational in nature; Study sponsor/Funder- University for Southern California

10.    ALEVIATE I-II: Task-related hippocampal activation in healthy individuals

Description: Changes in the brain associated with Alzheimer's disease (AD) begin years before people start showing symptoms. One of these early changes involves an abnormal increase in activity (hyperactivity) in the hippocampus (the memory area of the brain) that is caused by the toxic protein amyloid. This increase in activity can be described as small, silent, local seizures, similar to those seen in epilepsy but on a smaller, unrecognizable scale. A recent study found that levetiracetam (LEV), an antiepileptic drug, can reduce this hyperactivity to the same level seen in normal controls when given in small doses to people with amnestic Mild Cognitive Impairment (aMCI), the phase of AD when people first begin showing symptoms. A larger study is currently underway in patients with aMCI to confirm these findings.

Our study team would like to see if this hyperactivity can be detected and treated even earlier, before people start showing any changes in memory. For this purpose, we are going to conduct two studies. In ALEVIATE-1 (the current study), we are going to define the normal levels of activation in people with no symptoms and low risk of developing AD, since this information has not been published to date. We will then use these normal values in the second study, ALEVIATE-2, to find people with no symptoms but with hyperactivation and enroll them in a brief treatment trial with levetiracetam. ALEVIATE-1 will enroll 30 participants who are normal on cognitive testing and are negative for several key risk factors for AD (no APOE4 gene, and either no amyloid or no family history of dementia). These participants will have their hippocampal activation levels measured using functional magnetic resonance imaging (fMRI) while doing a memory task. We will also measure activity with combined electroencephalography (EEG) and magnetoencephalography (MEG), which is specialized for detecting subclinical hyperactivity.

Once we know what the normal levels of activation are, we will find people with higher levels (hyperactivation) and enroll them into ALEVIATE-2. We will look for these people among cognitively normal individuals who are at risk of Alzheimer’s disease. People enrolled into the study will be randomly allocated to one of two groups. One group will receive treatment with LEV for 4 weeks, then have a break of 4 weeks, then receive treatment with placebo for 4 weeks. The other group will have treatment with placebo for 4 weeks, then a break of 4 weeks, then treatment with LEV for 4 weeks. Hippocampal activation levels will be measured using fMRI at the start and end of each treatment period, along with cognitive tests and EEG-MEG. To reduce the potential for bias, the study staff and participants will not know which participant is in which group. Participants will also receive an amyloid PET scan to see if there is a correlation between the hyperactivity seen on fMRI and the amount of amyloid in their brain, as well as blood tests for genes and blood biomarkers potentially related to Alzheimer’s disease.

11.    REPHRASE: A Retinal Deep Phenotyping.TM Platform for Cerebral Amyloid Status Evaluation: A validation study

Description: This research study involves the evaluation of an investigational medical instrument, the Mydriatic Hyperspectral Retinal Camera (MHRC), as a simple and non-invasive way to image the retina to diagnose risk for Alzheimer’s disease. Investigational means that this device has not been approved by the United States Food and Drug Administration (FDA) or Health Canada (HC) for this purpose. The camera produces multiple images of the retina when exposed to light in very specific colors (over 90 specific colors). Alzheimer’s disease affects memory and attention. Alzheimer’s disease is identified by the presence of beta-amyloid plaques and neurofibrillary tangles (commonly known as tau tangles) found in the brain. These plaques and tangles contribute to the deterioration of certain brain functions.  The retina, the light sensitive layer lining the interior of your eye, is part of the central nervous system (directly connected to the brain), and this opens the possibility that a sign of Alzheimer’s disease may be detected in the eye. This research study will evaluate the possibility that Optina Diagnostics’ MHRC camera can detect the status of brain beta-amyloid plaques as determined by brain imaging (PET scan; see below). An eye examination will be conducted by an eye specialist (ophthalmologist or optometrist), and a series of retinal images will be captured using Optina Diagnostics’ MHRC. The study will compare the results from the PET scan with those from the Optina Diagnostics’ MHRC Camera (investigational device).

Study Type: Health Canada Regulated, device trial-Study Sponsor- OPTINA Inc.

12.    ADNI 4: (Study Status- awaiting protocol from sponsor)