Clinical trial NCT05104463: A Study of CST-2032 and CST-107 in Subjects With Mild Cognitive Impairment or Mild Dementia Due to Parkinson's or Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Dementia
Lead sponsor: CuraSen Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-03
Enrollment: 64
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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 ≤ 26.
* 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.
* Body weight greater or equal to 50 kg and body mass index (BMI) between 18 and 35 kg/m\^2, inclusive at Screening.
* Stable medical conditions for 30 days prior to Screening visit (e.g., controlled hypertension, dyslipidemia).
* Willing to follow the protocol requirements and comply with protocol restrictions.
* Capable of providing informed consent and complying with study procedures.
* Able to speak, understand and read English.

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.
* Prior and/or concurrent treatment with any investigational drug ≤90 days prior to dosing (Day 1), or ≤5 half-lives of the drug (whichever is longer), or current enrollment in any other study treatment or disease study, except for observational studies.
* Prior and/or concurrent treatment with any beta-AR agonists or beta-AR blockers (includes oral meds, IV or inhaled) or any meds that impact adrenergic signaling within the last month prior to Screening. Participants may be on stable doses of serotonin-noradrenaline reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs), or any treatment for ADHD including noradrenaline reuptake inhibitors (NRIs), or amphetamines within the last month prior to Screening.
* A history of heart failure, sinus bradycardia, second- or third-degree heart block, hypokalemia, attack of unconsciousness possibly associated with torsades de points or family history of Long QT Syndrome.
* Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse at Screening or Day -1.
* Suicidal ideation with actual intent or plan ("Yes" answer on the C-SSRS ideation items 4 or 5) within 3 months prior to study Screening.
* Positive screening test for human immunodeficiency virus (HIV), 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 surface antibody \[HbsAb\]) are eligible to participate in the study.
* Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
* Females who are breastfeeding.
* Any other reason for which the PI considers it is not in the best interest of the participant to undertake the study.

Primary outcomes:
measure: Treatment-emergent Adverse Events
timeFrame: Change from Baseline after 14 days of treatment
measure: Vital Signs
timeFrame: Change from Baseline after 14 days of treatment respectively (4 hours post dose)
measure: Electrocardiograms (ECGs)
timeFrame: Change from Baseline after 14 days of treatment respectively (4 hour post-dose)
Secondary outcomes:
measure: Change From Baseline in DSST Score
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in DSST Total Incorrect
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in CANTAB Stop Signal Reaction Time
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in CANTAB 5-Choice Reaction Time
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in CANTAB Paired Associates Learning Tool - Total Adjusted Errors
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in CANTAB Delayed Verbal Recognition
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in CANTAB Adaptive Tracking Mean Level of Difficulty Achieved
timeFrame: Change from Baseline after 7 and 14 days of treatment respectively.
measure: Change From Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT)
timeFrame: Change from Baseline after 14 days of treatment.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CuraSen Investigational Site
state: Arizona
city: Lafayette
country: United States
facility: CuraSen Investigational Site
state: California
city: Boca Raton
country: United States
facility: CuraSen Investigational Site
state: Florida
city: Bradenton
country: United States
facility: CuraSen Investigational Site
state: Florida
city: Lady Lake
country: United States
facility: CuraSen Investigational Site
state: Florida
city: Miami
country: United States
facility: CuraSen Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: CuraSen Investigational Site
state: Florida
city: Winter Park
country: United States
facility: CuraSen Investigational Site
state: Florida
city: New York
country: United States
facility: CuraSen Investigational Site
state: New York
city: Cincinnati
country: United States
facility: CuraSen Investigational Site
state: Ohio
city: Houston
country: United States
facility: CuraSen Investigational Site
state: Texas
city: Round Rock
country: United States
facility: CuraSen Investigational Site
state: Texas
city: Stafford
country: United States
facility: CuraSen Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: CuraSen Investigational Site
state: Utah
city: Christchurch
country: New Zealand
facility: CuraSen Investigational Site
Study officials:
affiliation: CuraSen Therapeutics, Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: