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Mild Cognitive Impairment (MCI)Phase 1NCT05033912

A Study of CST-2032 in Subjects With Cognitive Impairment

A Phase 1 study of Mild Cognitive Impairment (MCI) and Parkinson Disease (PD), run by CuraSen Therapeutics, Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study will evaluate the effects of CST-2032 when administered with pre-administered CST-107 on safety, tolerability, cognition, cerebral perfusion, and cerebral metabolism in patients with cognitive impairment. Read more about this study

Who is it for?
Ages 45 to 75 years
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Oct 2021to May 2022
Phase
Phase 1
Are there results?
None posted in the registry

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 45 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female aged 45-75 years at the time of informed consent.
  • Unless confirmed to be azoospermic (vasectomized or secondary to medical cause), males must agree to use a male condom plus partner use of an additional contraceptive method from the start of confinement or Day -1 up to 90 days after the last study drug administration when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant. Sperm donation is not allowed during this period. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a condom during each episode of penile-vaginal penetration.
  • Females of childbearing potential must have a negative serum pregnancy test during Screening and a negative urine pregnancy test before first dose of study drug. In addition, they must be willing to abstain from egg collection or donation from start of Screening through 90 days after the last study drug administration.
  • Females of childbearing potential (i.e., not postmenopausal or surgically sterile) who have a male partner must agree to one of the following options from signing of informed consent through 90 days after the last study drug administration: use of a highly effective method of birth control, or confirmed sterilization of a monogamous partner, or practice abstinence.
  • Females of non-childbearing potential may be enrolled if they are postmenopausal or have documented evidence of surgical sterilization.
  • Stable medical conditions for at least 3 months prior to Screening visit (e.g., hypertension, dyslipidemia)
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  • Stable use of vitamin E (up to 400 IU daily), estrogens, aspirin (75-300 mg daily), blood pressure medications (except for adrenergic agents), and cholesterol-lowering agents for at least 3 months prior to screening is allowed.
  • In generally good health based on medical and surgical history, BMI, physical examination, vital signs, 12-lead ECG and laboratory values, including hematology and chemistry values.
  • Clinical laboratory values within normal limits or, if abnormal, must be judged to be clinically insignificant.
  • Able to understand and sign the written Informed Consent Form (ICF).
  • Willing to follow the protocol requirements and comply with protocol restrictions.
  • In addition, for subjects with MCI:
  • Must meet the criteria for amnestic Mild Cognitive Impairment (MCI), as per the National Institute on Aging-Alzheimer's Association core clinical criteria.
  • No dementia according to International Classifications of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV.
  • A score of greater than or equal to one standard deviation below age and educational norms in the Digit Symbol Substitution Test (DSST) during screening.
  • A memory complaint reported by the subject or his/her partner.
  • Cognitive decline not primarily caused by vascular, traumatic, or medical problems.
  • Preserved basic activities of daily living and no more than minimal impairment.
  • In addition, for subjects with PD:
  • Parkinson's disease (PD) defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes, and without any other known or suspected cause of Parkinsonism
  • Modified Hoehn \& Yahr stage ≤ 3 during "On" period as documented in the 3 months prior to Screening.
  • Mini Mental Status Examination (MMSE) score ≥26.
  • If taking medications for PD, subjects on stable (≥3 months prior to Day 1) levodopa/carbidopa or levodopa/benserazide, monoamine oxidase type B inhibitors, dopamine agonists or catechol-O-methyltransferase inhibitors are allowed. Subjects on β-antagonists are not allowed.

Who cannot join

  • Female subjects who are pregnant or lactating.
  • History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, metabolic, psychological, or musculoskeletal disease.
  • Subjects with a history of malignant disease, including solid tumours and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
  • Calculated creatinine clearance of ≤60 mL/min.
  • Positive screening test for human immunodeficiency virus (HIV).
  • Positive screening test for hepatitis C antibody (HCV Ab) or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] at Screening). Subjects with immunity to hepatitis B (defined as negative HBsAg and positive hepatitis B core antibody [anti-HBc]) are eligible to participate in the study.
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  • Positive test for and current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening, or evidence of possible ongoing infection based on body temperature (> 37.3 oC), blood oxygen (<90 %) at the start of first confinement or Day -1.
  • History of epilepsy, seizure disorder or any unexplained black-outs.
  • Suicidal ideation with actual intent or plan ("Yes" answer on the Columbia-Suicide Severity Rating Scale [C-SSRS] ideation items 4 or 5) within 3 months prior to study Screening.
  • History of drug or alcohol abuse ≤12 months prior to Screening.
  • History of tobacco use including cigarettes, cigars, vapes or e-cigarettes ≤6 months prior to Screening.
  • A positive test for drugs of abuse, cotinine or alcohol during Screening or prior to dosing.
  • Unwilling or unable to abstain from alcohol or caffeine for 48 hours prior to dosing until end of each confinement or dosing period.
  • Current use of any prohibited medication, over-the-counter medication, or herbal supplements/products.
  • History of relevant cardiovascular disease including angina, hypertension (unless currently under control with stable medications), heart failure, coronary insufficiency, cardiac arrhythmias, diabetes mellitus, hyperthyroidism, convulsion disorders, bronchial asthma, clinically significant sinus bradycardia and greater than first degree conduction block.
  • Clinically significant abnormal clinical laboratory test values.
  • Clinically significant abnormalities in 12-lead ECG, including marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration of a QTcF interval >450 msec) at Screening.
  • Prior treatment with any investigational drug ≤30 days prior to dosing (Day 1), or ≤5 half-lives of the drug (whichever is longer), or current enrolment in any other study treatment or disease study.
  • Vaccinations ≤14 days prior to dosing.
  • Donation or loss of ≥500 mL of blood or plasma within 30 days prior to dosing.
  • Inability to undergo a clinical MRI of the brain without contrast.
  • Clinically significant brain abnormalities based on T1 weighted MRI during screening.
  • Any other reason which prompts the Principal Investigator to consider that it is not in the best interest of the subject to participate in the study.

About this study

Official title: An Open-Label Ascending Single-Dose, and Randomized, Double-blind, Placebo-controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CST-2032 in Healthy Volunteers and Subjects With Mild Cognitive Impairment or Parkinson's Disease

This study will evaluate the effects of CST-2032 when administered with pre-administered CST-107 on safety, tolerability, cognition, cerebral perfusion, and cerebral metabolism in patients with cognitive impairment.

Read the detailed description

This is a phase1, randomized sequence of placebo, low-, mid- and high-dose CST-2032 in Subjects with cognitive impairment. Sixteen (16) subjects with cognitive impairment will be enrolled. The first subject enrolled will be dosed as a sentinel. If no significant safety issues are noted in the sentinel subject, the remaining subjects will be dosed starting 24 hours after the Day 4 dose for the sentinel subject.

Subjects will have the option to attend all study visits as outpatients or be admitted for a 4-5-night confinement period at the research facility. Subjects will receive matching placebo for CTS-2032, 1mg, 3mg, and 9 mg CST-2032 two hours after a pre-administered dose of 3 mg CST-107 in a randomized sequence on Days 1, 2, 3 and 4.

Cognitive assessments (CANTAB) and a verbal fluency test will be administered daily. If operationally feasible, subjects will also undergo arterial spin labeling (ASL) magnetic resonance (MRI) imaging of the brain on Days 1 and 4.

Being tested
CST-2032, matching placebo for CST-2032, CST-107
Medical subject headings
Cognitive Dysfunction, Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CST-2032, matching placebo for CST-2032, CST-107Drug

    CST-2032 and matching placebo oral liquid; CST-107 white capsules

Study groups in NCT05033912
Study groupRoleWhat they receive
Treatment Sequence 1ExperimentalSubjects will receive daily doses of matching placebo for CST-2032 and CST-107 on Day 1, 1mg CST-2032 \& 3mg CST-107 on Day 2, 3mg CST-2032 \& 3mg CST-107 on Day 3, \& 9mg CST-2032 and 3mg CST-107 on Day 4.
Receives: Drug: CST-2032, matching placebo for CST-2032, CST-107
Treatment Sequence 2ExperimentalSubjects will receive daily doses of 1mg CST-2032 \& 3mg CST-107 on Day 1, 3mg CST-2032 \& 3mg CST-107 on Day 2, \& 9mg CST-2032 and 3mg CST-107 on Day 3, and matching placebo for CST-2032 and CST-107 on Day 4.
Receives: Drug: CST-2032, matching placebo for CST-2032, CST-107
Treatment Sequence 3ExperimentalSubjects will receive daily doses of 3mg CST-2032 \& 3mg CST-107 on Day 1, \& 9mg CST-2032 and 3mg CST-107 on Day 2, matching placebo for CST-2032 and CST-107 on Day 3, and 1mg CST-2032 \& 3mg CST-107 on Day 4.
Receives: Drug: CST-2032, matching placebo for CST-2032, CST-107
Treatment Sequence 4ExperimentalSubjects will receive daily doses of 9mg CST-2032 and 3mg CST-107 on Day 1, matching placebo for CST-2032 and CST-107 on Day 2, 1mg CST-2032 \& 3mg CST-107 on Day 3, and 3mg CST-2032 \& 3mg CST-107 on Day 4.
Receives: Drug: CST-2032, matching placebo for CST-2032, CST-107

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Treatment-Emergent Adverse Events

    The number of subjects experiencing treatment-emergent adverse events after receiving CST-2032 doses of 1mg, 3mg and 9mg compared to placebo

    Measured: Day -1, Days 1-4 of the treatment period

  2. Vital Signs

    Change from Baseline in supine blood pressure (diastolic blood pressure and systolic blood pressure) after CST-2032 doses of 1mg, 3mg, and 9mg compared to placebo

    Measured: Day -1, Days 1-4 of the treatment period

  3. Electrocardiograms (ECGs)

    Change from Baseline in QTc interval using the Fredericia (QTcF) and Bazett (QTcB) corrections after CST-2032 doses of 1mg, 3mg, and 9mg compared to placebo

    Measured: Day -1, Days 1-4 of the treatment period

Secondary outcomes (7)

  1. Change from Baseline in CANTAB Reaction Time Task

    Measures changes in cognition by testing psychomotor speed (selecting a flashing circle on a touch tablet screen as quickly as possible).

    Measured: Day -1, Days 1-4 of the treatment period

  2. Change from Baseline in CANTAB Paired Associates Learning Test

    Measures changes in cognition by testing attention (remembering the location of an abstract pattern on a touch tablet screen).

    Measured: Day -1, Days 1-4 of the treatment period

  3. Change from Baseline in CANTAB Verbal Recognition Memory

    Measures changes in cognition by testing memory (recall of 18 words flashed onto a touch tablet screen).

    Measured: Day -1, Days 1-4 of the treatment period

  4. Change from Baseline in CANTAB Rapid Visual Information Processing

    Measures changes in cognition by testing sustained attention, response accuracy, target sensitivity and reaction times. Single digits appear in random order in the center of a touch tablet screen and subjects must detect a series of 3-digit target sequences and respond by touching the button at the bottom of the screen when they see the final number of the sequence.

    Measured: Day -1, Days 1-4 of the treatment period

  5. Change from Baseline in CANTAB Adaptive Tracking Task

    Measures changes in visual and motor coordination and vigilance. In this task, a small circle (target) continuously moves across the screen in a semi-randomized fashion, so as to minimize the subject's ability to predict the trajectory of the target. The subject is instructed to use his/her finger on the touch screen to move a small dot so that it is consistently within the center of the moving target on the screen. During the test, the speed of the circle is adjusted in response to the subject's ability to keep the dot in the circle, ensuring that the test is adapted to the individual subject.

    Measured: Day -1, Days 1-4 of the treatment period

  6. Change from Baseline in Verbal Fluency Test

    Measures changes in cognition by assessing executive function, and requires the generation of words from initial letters or belonging to a specific category under a time constraint. Subjects are given 1 minute to say aloud as many words they can think of that begin with the letter F, avoiding repetitions or the same words with different endings. The total score is the number of correct words generated. Subjects are also given 1 minute to say aloud as many animals they can think of, avoiding repetitions. The total score is the number of animals generated.

    Measured: Day -1, Days 1-4 of the treatment period

  7. Change from Baseline in ASL MRI scans of the brain

    Measures cerebral blood flow (CBF). CBF is defined as the volume of blood delivered to a given mass of brain tissue in a given time.

    Measured: Pre- and Post-dose on Days 1 and 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2021
  2. Study startOct 2021 (estimated)
  3. Primary completionMar 2022 (estimated)
  4. Study completionMay 2022 (estimated)

Why it stopped: Business reasons

Resources

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
This is a phase1, randomized sequence of placebo, low-, mid- and high-dose CST-2032 after a pre-administered dose of 3 mg CST-107.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05033912
Sponsor's protocol ID
CST2032-CLIN-007
Status last verified
Oct 2021
First submitted
24 Aug 2021
Last updated
28 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study of Mild Cognitive Impairment (MCI) and Parkinson Disease (PD), run by CuraSen Therapeutics, Inc..

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 23 inclusion and 23 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: withdrawn, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Treatment-Emergent Adverse Events (time frame: Day -1, Days 1-4 of the treatment period). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05033912.

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 28 Oct 2021.

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