A study to investigate if CST-103 and CST-107 has an effect on the brain in patients with progressive disease of the nervous system.

Phase 1

• Conditions: Patients with Parkinson’s Disease with REM sleep behaviour disorder, Mild Cognitive Impairment, Dementia with Lewy Bodies and Parkinson’s Disease Dementia.; MedDRA version: 24.0Level: LLTClassification code 10012284Term: Dementia due to Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 21.1Level: LLTClassification code 10009846Term: Cognitive impairmentSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: PTClassification code 10067889Term: Dementia with Lewy bodiesSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-006067-28-BE
• Lead Sponsor: CuraSen Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-18
• Last Update Posted: 7 February 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Cohort A:Subjects with RBD+PD:
1.Male or female subjects = 40 and = 80 years of age, at time of informed consent.
2.Subject diagnosed with Parkinson’s Disease, as defined by the United Kingdom Parkinson Disease Brain Bank criteria, associated with REM sleep behaviour disorder (RBD+PD), diagnosed according to the International Classification of Sleep Disorders, Third Edition (ICSD-3) (albeit documentation by polysomnography is not required) and positive response to the REM Sleep Behaviour Disorder Single-Question Screen (RBD1Q).
3.Subject who is Modified Hoehn & Yahr = stage 1 and = stage 3 during On” period as documented in the 3 months prior to Screening or completed at Screening.
4.Montreal Cognitive Assessment (MoCA) score = 18 and = 28.
5. Intentionally left blank
Subjects with MCI:
6.Male or female subjects = 50 and = 80 years of age, at time of informed consent.
7.Subjects who meet the criteria for amnestic Mild Cognitive Impairment (MCI) as per the National Institute on Aging-Alzheimer's Association core clinical criteria.
8.Montreal Cognitive Assessment (MoCA) score = 18 and = 26.
9.No dementia according to the International Classifications of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV.
10.A memory complaint reported by the subject or his/her partner, family member or caregiver
11.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.
12.Cognitive decline not primarily caused by vascular, traumatic, or medical problems (alternative causes of cognitive decline are ruled out).
13.Intentionally left blank

Cohort B: Subjects with Dementia with Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD):
14.Male or female subjects = 50 and = 80 years of age, at time of informed consent.
15.A diagnosis of dementia associated with Dementia with Lewy Bodies.
16.Documented cognitive fluctuations endorsed on the Dementia Cognitive Fluctuation Scale (DCFS) with a combined score of >8 in items 4, 11, 12 and 14.
17.Montreal Cognitive Assessment (MoCA) score = 18 and = 26.
18.Subject having informant or caregiver throughout the study who will submit written consent to cooperate with this study, who routinely stays with subject 12 hours or more a week, assists with treatment compliance, provides assessments and is able to escort the subject on required visits to study institution.
19.Subject who is Modified Hoehn & Yahr = stage 1 and = stage 3 during On” period as documented in the 3 months prior to Screening or completed at Screening.
20.Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI.

For ALL Subjects:
21.Unless confirmed to be azoospermic (vasectomized or secondary to medical cause), males must agree to use a male condom from Day 1 throughout the study 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 Follow-Up Visit.
22.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:
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Exclusion Criteria

1.Subjects with poorly controlled hypertension despite lifestyle modifications and/or pharmacotherapy.
2.Subjects with pulmonary disease, including asthma if requiring use of a ß2-adrenergic bronchodilator, or evidence of clinically significant moderate or severe pulmonary symptoms.
3.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.
4.Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or meeting DSM-IV diagnostic criteria for psychotic disorders, such as Schizophrenia or Bipolar Disorder, or have unstable concomitant psychiatric symptomatology that is not believed by the Investigator to be associated with PDD or DLB.
5.Evidence of any significant clinical disorder or laboratory finding (or in the case of potassium levels below the normal range)that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine (excluding managed hypo and hyperthyroidism), metabolic, renal or other systemic disease or laboratory abnormality.
6.Participants with a history of malignant disease, including solid tumors and hematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
7.Any clinically significant illness or disease (apart from those typically associated with NDD) as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening.
8.Clinically significant abnormalities of ECG, including QTcF > 450 ms, for males and QTcF > 470 ms for females, and/or HR < 50 beats per minute, or evidence of clinically significant bundle branch blocks, as indicated by 12-lead ECG in a supine position at Screening or during the Lead-In Period.
9.A calculated creatinine clearance of =70 mL/min according to the Cockcroft-Gault equation.
10.Current use of any prohibited prescription medication, over-the-counter medication, or herbal supplements/products (listed in protocol section 5.4), during Screening or throughout study, unless approved by both the Investigator and the Sponsor Medical Monitor.
11. Known hypersensitivity to Spiropent (clenbuterol), Corgard (nadolol) or intolerance to lactose. Subjects with hereditary galactose intolerance (e.g., galactosemia, lactase deficiency or glucose galactose malabsorption) should be excluded.
12.Prior 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.
13.Prior treatment with any ß-AR agonists or ß-AR blockers (includes oral meds, IV or inhaled) or any meds that impact adrenergic signalling within the last month prior to Screening.
14.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.
15.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.
16.Po

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified