A Study of CST-2032 in Subjects With Cognitive Impairment

NCT05033912 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CST2032-CLIN-007
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Mild Cognitive Impairment (MCI); Parkinson Disease (PD)

Outcome Measures

Primary Outcomes (3)

• 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

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

• 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

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

• 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

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

Secondary Outcomes (7)

• Change from Baseline in CANTAB Reaction Time Task

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

• Change from Baseline in CANTAB Paired Associates Learning Test

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

• Change from Baseline in CANTAB Verbal Recognition Memory

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

• Change from Baseline in CANTAB Rapid Visual Information Processing

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

• Change from Baseline in CANTAB Adaptive Tracking Task

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

Study Arms (4)

Treatment Sequence 1

EXPERIMENTAL

Subjects 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.

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

Treatment Sequence 2

EXPERIMENTAL

Subjects 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.

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

Treatment Sequence 3

EXPERIMENTAL

Subjects 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.

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

Treatment Sequence 4

EXPERIMENTAL

Subjects 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.

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

Interventions

CST-2032, matching placebo for CST-2032, CST-107 DRUG

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

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• CuraSen Therapeutics, Inc.: lead

MeSH Terms

Conditions

Cognitive Dysfunction; Parkinson Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Chief Medical Officer

  CuraSen Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: September 5, 2021
• Study Start: October 1, 2021
• Primary Completion: March 1, 2022
• Study Completion: May 1, 2022
• Last Updated: October 28, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share