A Phase 2a, Randomized, Placebo-Controlled, Double-Blind, Crossover Study to Evaluate the Safety, Tolerability and Effects of CST-2032 and CST-107 on Cognition in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease
Overview
- Phase
- Phase 2
- Intervention
- CST-2032, matching placebo for CST-2032, CST-107, matching placebo for CST-107
- Conditions
- Mild Cognitive Impairment
- Sponsor
- CuraSen Therapeutics, Inc.
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Treatment-emergent Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 2a, randomized, placebo-controlled, double-blind, crossover study to evaluate the effects CST-2032 administered with CST-107 on cognition in participants with Mild Cognitive Impairment (MCI) or mild dementia.
Detailed Description
Approximately 60 participants will be enrolled in a 2 period, 2-way crossover design following study eligibility confirmation during the screening period. During each treatment period, subjects will receive daily doses of CST-2032 administered with CST-107 or matching placebo for 14 days. Each treatment period will be separated by a washout period of at least 7 days and up to 21 days. All participants will complete clinical, cognitive and pharmacodynamic assessments during each treatment period. PK blood samples will be collected prior to, during and after study medication administration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female participants ≥ 50 and ≤ 85 years of age at time of informed consent.
- •Diagnosis of mild cognitive impairment OR mild dementia due to either: Parkinson's disease associated with REM sleep behavior disorder (RBD+PD) and positive response to the RBD Single-Question Screen (RBD1Q) and without hallucinations; OR Alzheimer's Disease (AD).
- •For participants taking medications: stable dose and regimen for at least 30 days (90 days for anti-psychotic medications) prior to Day -1 and the dose must remain unchanged through the End of Study Visit unless required for management of adverse events (AEs).
- •Cognitive decline not primarily caused by vascular, traumatic, or medical problems (alternative causes of cognitive decline are ruled out).
- •Adequate visual and auditory abilities and motor skills to perform all aspects of the cognitive and functional assessments.
- •Has a spouse or caregiver who can accompany the subject at specified study visits (if required based on cognitive function).
- •Montreal Cognitive Assessment (MoCA) score ≥ 14 and ≤
- •Unless confirmed to be azoospermic (vasectomized or secondary to medical cause), males must agree to use a male condom from Day -1 until the End of Study visit when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant. 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 until after the End of Study Visit.
- •Females of childbearing potential (i.e., not postmenopausal or surgically sterile) who have a male partner must have a negative serum pregnancy test result and must agree to one of the following from start of Screening through 30 days after the last study medication administration: use a highly effective method of birth control; or monogamous relationship with a male partner of confirmed sterility; or practice complete abstinence.
- •Females of non-childbearing potential may be enrolled if it is documented that they are postmenopausal.
Exclusion Criteria
- •Participants with poorly controlled hypertension despite lifestyle modifications and/or pharmacotherapy.
- •Participants with pulmonary disease, including asthma, or evidence of clinically significant moderate or severe pulmonary symptoms.
- •Clinical signs indicating syndromes such as corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontotemporal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, or Babinski sign.
- •Current evidence of epilepsy, focal brain lesion, head injury with loss of consciousness or meeting DSM-V diagnostic criteria for psychotic disorders, such as schizophrenia or bipolar disorder, or have unstable concomitant psychiatric symptomatology (participants with psychotic disorders may be enrolled if their condition is effectively managed, i.e., must be receiving stable doses of anti-psychotic medications(s) 90 days prior to randomization and must remain on that dose throughout both treatment periods.)
- •Evidence of any significant clinical disorder or laboratory finding (e.g., potassium levels below normal range) that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, moderate and severe impairment of hepatic function (as defined by the National Cancer Institute Organ Dysfunction Working Group), cardiovascular, pulmonary, gastrointestinal, endocrine (including thyrotoxicosis, excluding managed hypo and hyperthyroidism), immunologic, dermatologic, neurologic, musculoskeletal, metabolic, renal, or other systemic disease or laboratory abnormality.
- •Participants with a history of malignant disease within 5 years, including solid tumors and hematologic malignancies (exceptions: \[a\] basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured; \[b\] low-grade adenocarcinoma of the prostate, which are slow growing, and are unlikely to progress or metastasize during the clinical trial).
- •Any clinically significant medical condition or disease as determined by medical history, physical examination 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted that, in the view of the Principal Investigator, will interfere with participation in the study or interpretation of results.
- •Clinically significant abnormalities of 12-lead ECG (as determined by a central reader), including QTcF \> 440 ms, for males and females, and/or HR \< 50 beats per minute, or evidence of bundle branch blocks, as indicated on the Mean ECG Analysis Report during the screening Period.
- •A calculated creatinine clearance of ≤60 mL/min according to the Cockcroft-Gault equation.
- •Current use of any prohibited prescription medication, over-the-counter medication, or herbal supplements including green tea products during Screening or throughout study, unless approved by both the Investigator and the Sponsor Medical Monitor.
Arms & Interventions
CST-2032 (3mg)/CST-107 (3mg) to Placebo
Participants will receive daily doses of CST-2032 (3mg) co-administered with CST-107 (3mg) for 14 days, followed by a washout period of no drug for 7 days, followed by matching placebo for CST-2032 and matching placebo for CST-107 for 14 days.
Intervention: CST-2032, matching placebo for CST-2032, CST-107, matching placebo for CST-107
Placebo to CST-2032 (3mg)/CST-107 (3mg)
Participants will receive matching placebo for CST-2032 and matching placebo for CST-107 for 14 days followed by a washout period of no drug for 7 days, followed by daily doses of CST-2032 (3mg) co-administered with CST-107 (3mg) for 14 days.
Intervention: CST-2032, matching placebo for CST-2032, CST-107, matching placebo for CST-107
Outcomes
Primary Outcomes
Treatment-emergent Adverse Events
Time Frame: Change from Baseline after 14 days of treatment
The number of participants experiencing treatment-emergent adverse events after receiving 3mg CST-2032 co-administered with 3mg CST-107 compared to placebo
Vital Signs
Time Frame: Change from Baseline after 14 days of treatment respectively (4 hours post dose)
Change from Baseline in supine blood pressure (diastolic blood pressure and systolic blood pressure) after CST-2032 co-administered with CST-107 compared to placebo
Electrocardiograms (ECGs)
Time Frame: Change from Baseline after 14 days of treatment respectively (4 hour post-dose)
Change from Baseline in QTc interval using the Fredericia (QTcF) corrections after treatment with CST-2032 co-administered with CST107 compared to placebo
Secondary Outcomes
- Change From Baseline in DSST Score(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in DSST Total Incorrect(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in CANTAB Stop Signal Reaction Time(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in CANTAB 5-Choice Reaction Time(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in CANTAB Paired Associates Learning Tool - Total Adjusted Errors(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in CANTAB Delayed Verbal Recognition(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in CANTAB Adaptive Tracking Mean Level of Difficulty Achieved(Change from Baseline after 7 and 14 days of treatment respectively.)
- Change From Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT)(Change from Baseline after 14 days of treatment.)