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A Study of the Effects of CY6463 in Participants With Alzheimer's Disease With Vascular Pathology

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04798989
Recruitment Status : Recruiting
First Posted : March 16, 2021
Last Update Posted : June 10, 2022
Sponsor:
Information provided by (Responsible Party):
Cyclerion Therapeutics

Brief Summary:
This study is being conducted to test the safety, tolerability, and pharmacokinetics of the investigational drug CY6463 compared with placebo in individuals who are aged 60 years or older and have Alzheimer's disease (AD) along with common cardiovascular risk factors.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease With Vascular Pathology Drug: CY6463 Drug: Placebo Phase 2

Detailed Description:

CY6463 is an investigational drug being developed as a symptomatic and potentially disease-modifying therapy for Alzheimer's disease (AD) and other serious central nervous system disorders. As a soluble guanylate cyclase (sGC) stimulator, CY6463 can cross the blood-brain barrier and boosts the activity of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway. This signaling pathway is important in many aspects of brain health, including in the control of blood flow in the brain, how brain cells use energy, and how those cells communicate with one another. Impairment of this pathway is a critical part of the origin of many neurodegenerative diseases that can cause a loss of brain function including memory and decision-making abilities. There are clear links between disrupted NO signaling and impaired brain function in patients with AD and vascular pathology (ADv). ("Vascular pathology" refers to abnormalities of the blood vessels that are more likely to occur when a person has cardiovascular risk factors like high blood pressure, diabetes, and/or obesity.) It is hypothesized that CY6463 may help patients with ADv maintain or recover some of their original cognitive function.

In this study, participants will be randomized to receive approximately 87 sequential days (~3 months) of study drug (CY6463 or placebo) once daily (QD) and will complete 7 scheduled site visits over the course of the study, from Screening through Follow up.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CY6463 When Administered to Participants With Alzheimer's Disease and Vascular Pathology
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CY6463 Drug: CY6463
CY6463 Oral Tablet

Placebo Comparator: Placebo Drug: Placebo
Placebo Oral Tablet




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) from study drug initiation through Follow-up [ Time Frame: From first dose of study treatment through ~14 (±4) days after the final dose ]
    TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of the Follow-up period



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provide written informed consent prior to the performance of any protocol-specified procedure or, if unable to provide informed consent due to cognitive status, provides assent to participate, with a legally authorized representative (LAR) providing written informed consent on behalf of the participant.
  2. 60 years of age or older
  3. Meets core clinical criteria for probable AD dementia according to the 2011 National Institute on Aging-Alzheimer's Associated guidelines. Can be based on medical history.
  4. Mini-Mental State Examination (MMSE) score of 20 to 26 (inclusive)
  5. Confirmation of AD pathophysiology
  6. At least 2 cardiovascular risk factors per protocol criteria
  7. Magnetic resonance imaging (MRI) scan (existing MRI obtained ≤6 months before Screening is acceptable) findings of mild-to-moderate subcortical small-vessel disease
  8. If receiving concomitant or chronic medication(s), has had no change for ≥4 weeks before study drug initiation and has no plans to alter the regimen(s) during the study
  9. If male, agrees to refrain from donating sperm from the Screening visit through 90 days after taking the final study drug dose
  10. If male, agrees to use protocol-specified, effective contraception methods from the signing of the informed consent form (ICF) until ≥90 days after taking the final study drug dose.
  11. If female, is postmenopausal/not of reproductive potential defined per protocol
  12. Agrees to the study procedures, including undergoing lumbar puncture for cerebrospinal fluid (CSF) samples

Exclusion Criteria:

  1. Severe visual, auditory, social, or cognitive impairment
  2. Dementia-related disorder other than AD or vascular dementia (eg, Parkinson's disease, Huntington's disease, frontotemporal dementia, schizophrenia, Lewy body dementia)
  3. Symptomatic large-vessel disease, symptomatic carotid artery disease, large vessel infarcts, or strategic lacunar infarcts or infarcts>15 mm
  4. History of significant central nervous system (CNS) trauma that has affected brain function
  5. Low blood pressure (BP), defined as systolic BP ≤90 mmHg or diastolic BP ≤60 mmHg.
  6. Orthostatic hypotension.
  7. Unable to undergo MRI
  8. Unable to undergo lumbar puncture procedure
  9. Unable to participate in electroencephalography (EEG) protocol due to hearing impairment or inability to tolerate EEG cap or headphones
  10. Uncontrolled or unstable chronic disease
  11. Kidney impairment requiring dialysis; history of renal transplant
  12. Needs continuous direct medical care and nursing supervision.
  13. Family history of short QT syndrome or long QT syndrome
  14. Clinically significant cardiac involvement
  15. History of cancer. Exceptions: localized cutaneous basal or squamous cell carcinoma in the last 5 years, low-grade localized prostate/cervical cancers, or previous localized prostate/cervical cancers that have a low likelihood of recurrence
  16. Is not suited for study participation in the clinical judgment of the investigator

Additional inclusion and exclusion criteria apply, per protocol.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04798989


Contacts
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Contact: Meghan Bratton 857-338-3339 mbratton@cyclerion.com

Locations
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United States, Arizona
Clinical Endpoints Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Donnell Carmichael    480-566-9090    dcarmichael@clinicalendpoints.com   
United States, Florida
Optimus U Corp Recruiting
Miami, Florida, United States, 33125
Contact: Fermin Nieto    305-702-0024    fermin@optimusu.com   
United States, Hawaii
Hawaii Pacific Neurosciences, LLC Recruiting
Honolulu, Hawaii, United States, 96817
Contact: Catherine Mitchell    808-564-6141    cmitchell@hawaiineuroscience.com   
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Kimberly Hope    859-257-6507    Kimberly.Hope@uky.edu   
Contact: Keisha Jones    (859) 218-4980    kcl.jones@uky.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kate Cropp    617-643-4802    actrustudies@mgh.harvard.edu   
Contact: Kate LaCasse    617-634-4047    klacasse1@mgh.harvard.edu   
Sponsors and Collaborators
Cyclerion Therapeutics
Investigators
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Study Director: Chad Glasser, PharmD Cyclerion Therapeutics
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Responsible Party: Cyclerion Therapeutics
ClinicalTrials.gov Identifier: NCT04798989    
Other Study ID Numbers: C6463-202
First Posted: March 16, 2021    Key Record Dates
Last Update Posted: June 10, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cyclerion Therapeutics:
Alzheimer's disease
AD
ADv
CY6463
Subcortical small-vessel disease
Elderly
60 and older
Probable AD dementia
Vascular dementia
Mixed dementia
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders