Alzheimer's Disease With Vascular PathologyPhase 2NCT04798989
A Study of the Effects of CY6463 in Participants With Alzheimer's Disease With Vascular Pathology
A Phase 2 study testing CY6463 in people with Alzheimer's Disease With Vascular Pathology, run by Tisento Therapeutics at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Alzheimer's Disease With Vascular Pathology
- What is being tested?
- CY6463
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 5 sitesUnited States
- Study dates
- 2 Nov 2021to 28 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 60 years of age or older
- 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.
- Mini-Mental State Examination (MMSE) score of 20 to 26 (inclusive)
- Confirmation of AD pathophysiology
- At least 2 cardiovascular risk factors per protocol criteria
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- Magnetic resonance imaging (MRI) scan (existing MRI obtained ≤6 months before Screening is acceptable) findings of mild-to-moderate subcortical small-vessel disease
- 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
- If male, agrees to refrain from donating sperm from the Screening visit through 90 days after taking the final study drug dose
- 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.
- If female, is postmenopausal/not of reproductive potential defined per protocol
- Agrees to the study procedures, including undergoing lumbar puncture for cerebrospinal fluid (CSF) samples
Who cannot join
- Severe visual, auditory, social, or cognitive impairment
- Dementia-related disorder other than AD or vascular dementia (eg, Parkinson's disease, Huntington's disease, frontotemporal dementia, schizophrenia, Lewy body dementia)
- Symptomatic large-vessel disease, symptomatic carotid artery disease, large vessel infarcts, or strategic lacunar infarcts or infarcts>15 mm
- History of significant central nervous system (CNS) trauma that has affected brain function
- Low blood pressure (BP), defined as systolic BP ≤90 mmHg or diastolic BP ≤60 mmHg.
- Orthostatic hypotension.
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- Unable to undergo MRI
- Unable to undergo lumbar puncture procedure
- Unable to participate in electroencephalography (EEG) protocol due to hearing impairment or inability to tolerate EEG cap or headphones
- Uncontrolled or unstable chronic disease
- Kidney impairment requiring dialysis; history of renal transplant
- Needs continuous direct medical care and nursing supervision.
- Family history of short QT syndrome or long QT syndrome
- Clinically significant cardiac involvement
- 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
- Is not suited for study participation in the clinical judgment of the investigator
- Additional inclusion and exclusion criteria apply, per protocol.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Hawaii Pacific Neurosciences, LLC
Honolulu, Hawaii, 96817
University of Kentucky
Lexington, Kentucky, 40536
Optimus U Corp
Miami, Florida, 33125
Clinical Endpoints
Scottsdale, Arizona, 85258
About this study
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
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.
Read the 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.
- Being tested
- CY6463, Placebo
- Keywords
- Alzheimer's disease, AD, ADv, CY6463, Subcortical small-vessel disease, Elderly, 60 and older, Probable AD dementia, Vascular dementia, Mixed dementia
- Medical subject headings
- Alzheimer Disease, Dementia, Vascular, Mixed Dementias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CY6463Drug
Also called IW-6463, zagociguat
CY6463 Oral Tablet
PlaceboDrug
Placebo Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| CY6463 | Experimental | CY6463 once daily (QD) for approximately 87 sequential days. Receives: Drug: CY6463 |
| Placebo | Placebo comparator | Placebo QD for approximately 87 sequential days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-emergent Adverse Events (TEAEs) From Study Drug Initiation Through Follow-up
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
Measured: From first dose of study treatment through ~14 (±4) days after the final dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2021
- Study start2 Nov 2021
- Primary completion28 Nov 2022
- Study completion28 Nov 2022
Why it stopped: Due to enrollment challenges
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's Disease With Vascular PathologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tisento Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Tisento Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04798989
- Sponsor's protocol ID
- C6463-202
- Status last verified
- Oct 2024
- First submitted
- 11 Mar 2021
- Last updated
- 30 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04798989
- Acronym / sponsor ID
- C6463-202
- Keywords
- Alzheimer's disease, AD, ADv, CY6463, Subcortical small-vessel disease, Elderly, 60 and older, Probable AD dementia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to enrollment challenges
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Tisento TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2021 (actual)
- Primary completion
- 28 Nov 2022 (actual)
- Study completion
- 28 Nov 2022 (actual)
- First posted
- 16 Mar 2021 (actual)
- Results
- Posted 30 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CY6463 | Experimental | Drug: CY6463CY6463 once daily (QD) for approximately 87 sequential days. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo QD for approximately 87 sequential days. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- 60 years of age or older
- 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.
- Mini-Mental State Examination (MMSE) score of 20 to 26 (inclusive)
- Confirmation of AD pathophysiology
Key exclusion criteria (17 listed)
- Severe visual, auditory, social, or cognitive impairment
- Dementia-related disorder other than AD or vascular dementia (eg, Parkinson's disease, Huntington's disease, frontotemporal dementia, schizophrenia, Lewy body dementia)
- Symptomatic large-vessel disease, symptomatic carotid artery disease, large vessel infarcts, or strategic lacunar infarcts or infarcts>15 mm
- History of significant central nervous system (CNS) trauma that has affected brain function
- Low blood pressure (BP), defined as systolic BP ≤90 mmHg or diastolic BP ≤60 mmHg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CY6463Also: IW-6463, zagociguatCY6463 Oral Tablet | Drug | CY6463 |
| PlaceboPlacebo Oral Tablet | Drug | Placebo |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Tisento Therapeutics
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CY6463 in people with Alzheimer's Disease With Vascular Pathology, run by Tisento Therapeutics at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2024.