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A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders (CLIN-011)

Primary Purpose

Mild Cognitive Impairment, Lewy Body Dementia, Parkinson's Disease Rapid Eye Movement Sleep Behavior Disorder, Parkinson's Disease Dementia

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CST-103, CST-107, matching placebo
Sponsored by
CuraSen Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment, Lewy Body Dementia, Parkinson's Disease Rapid Eye Movement Sleep Behavior Disorder, Parkinson's Disease Dementia

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with RBD+PD:

  • Male or female subjects ≥ 40 and ≤ 80 years of age, at time of informed consent.
  • Diagnosed with Parkinson's Disease, as defined by the United Kingdom Parkinson Disease Brain Bank criteria, associated with REM sleep behavior disorder (RBD+PD)
  • Modified Hoehn & Yahr ≥ stage 1 and ≤ stage 3 during "On" period as documented in the 3 months prior to Screening or completed at Screening.
  • Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 28.
  • Hospital Anxiety and Depression Scale (HADS) Depression Sub-score ≥ 8.

Subjects with MCI:

  • Male or female subjects ≥ 50 and ≤ 80 years of age, at time of informed consent.
  • Meet the criteria for amnestic Mild Cognitive Impairment (MCI) as per the National Institute on Aging-Alzheimer's Association core clinical criteria.
  • Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 26.
  • No dementia according to the International Classifications of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV.
  • Memory complaint reported by the subject or his/her partner, family member or caregiver.
  • Score of greater than or equal to one standard deviation below age and educational norms in the Digit Symbol Substitution Test (DSST) during Screening.
  • Cognitive decline not primarily caused by vascular, traumatic, or medical problems.
  • HADS Depression Sub-score ≥ 8.

Subjects with Dementia with Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD):

  • Male or female subjects ≥ 50 and ≤ 80 years of age, at time of informed consent.
  • Diagnosis of dementia associated with Dementia with Lewy Bodies or Parkinson's disease (PDD).
  • Documented cognitive fluctuations endorsed on the Dementia Cognitive Fluctuation Scale (DCFS) with a combined score of ≥8 in items 4, 11, 12 and 14.
  • Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 26.
  • Have informant or caregiver throughout the study who will submit written consent to cooperate with this study, who routinely accompanies and/or 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.
  • Modified Hoehn & Yahr ≥ stage 1 and ≤ stage 3 during "On" period as documented in the 3 months prior to Screening or completed at Screening.
  • Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI.

For ALL Subjects:

  • 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.
  • 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 reliable 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/m2, inclusive at Screening.
  • Stable medical conditions for 3 months 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. Subjects who are unable to provide consent may use a Legally Authorized Representative.

Exclusion Criteria:

  • Poorly controlled hypertension despite lifestyle modifications and/or pharmacotherapy.
  • Pulmonary disease, including asthma if requiring the use of a β2-Adrenergic bronchodilator, 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 frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, or Babinski sign.
  • 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.
  • Evidence of any significant clinical disorder or laboratory finding (or in the case of potassium levels below normal range) that renders the participant unsuitable for receiving an investigational drug.
  • 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).
  • Any clinically significant illness or disease as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening.
  • 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.
  • Calculated creatinine clearance of ≤70 mL/min according to the Cockcroft-Gault equation.
  • Current use of any prohibited prescription medication, over-the-counter medication, or herbal supplements/products.
  • 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.
  • Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse.
  • Active suicidal ideation within 3 months prior to study Screening.
  • 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).
  • Positive screening test for human immunodeficiency virus (HIV).
  • Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • Contraindications to wearing the BioStamp digital device sensors, which include but are not limited to implanted pacemakers, defibrillators, or other active implantable devices.
  • Known allergies or hypersensitivities to adhesives or hydrogel.
  • Other reasons for which the PI considers it is not in the best interest of the participant to undertake the study.

Sites / Locations

  • The University of Sydney
  • Wesley Medical Research Ltd
  • Royal Melbourne Hospital
  • NZBRI
  • MAC
  • MAC
  • MAC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

CST-103/CST-107 to Placebo

Placebo to CST-103/CST-107

Arm Description

Subjects will receive daily doses of CST-103 co-administered with CST-107 for 14 days, followed by a washout period of no drug for 14 days, followed by matching placebo for CST-103 and matching placebo for CST-107 for 14 days.

Subjects will receive daily doses of matching placebo for CST-103 co-administered with matching placebo for CST-107 for 14 days, followed by a washout period of no drug for 14 days, followed by daily doses of CST-103 co-administered with CST-107 for 14 days.

Outcomes

Primary Outcome Measures

Change from Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT)
Faces with six different basic emotions (happiness, fear, anger, disgust, sadness, surprise) are briefly displayed on a screen and participants are required to indicate the expression of the face via a button-press.
Change from Baseline in Cognitive Fluctuations
Electroencephalogram (EEG), Activity Tracking, Pupil measurements, Dementia Cognitive Fluctuation Scale (DCFS)

Secondary Outcome Measures

Change from Baseline in CANTAB Cognitive Assessments
Measures changes in cognition by testing psychomotor speed, attention, and memory via a touch tablet
Digital wearable device (BioStamp)
A wireless device that measures physical activity and sleep while at home

Full Information

First Posted
January 29, 2021
Last Updated
May 30, 2023
Sponsor
CuraSen Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04739423
Brief Title
A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders
Acronym
CLIN-011
Official Title
A Phase II, Randomized, Placebo-Controlled, Double-Blind, Crossover, Study of the Pharmacodynamic Effects of CST-103 Co-administered With CST-107 on the Central Nervous System in Subjects With Neurodegenerative Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 28, 2021 (Actual)
Primary Completion Date
July 4, 2022 (Actual)
Study Completion Date
July 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CuraSen Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase II, randomized, placebo-controlled, double-blind, crossover study on the CNS and pharmacodynamic effects of CST-103 co-administered with CST-107 in 4 subject populations with Neurodegenerative Disorders.
Detailed Description
Approximately 40 subjects with Parkinson's Disease (PD) with REM Sleep Behavior Disorder (RBD) and Depressive Symptoms, Mild Cognitive Impairment (MCI) with Depressive Symptoms, Dementia with Lewy Bodies (DLB) with Cognitive Fluctuations, and Parkinson's Disease Dementia (PDD) with Cognitive Fluctuations will be enrolled in a 2 period, 2-way crossover design following study eligibility confirmation during the screening period. The number of subjects enrolled in each cohort may change as emerging data are reviewed from this and other studies. During each treatment period, subjects will receive daily doses of CST-103 co-administered with CST-107 or matching placebo for 14 days. Each treatment period will be separated by a washout period of 14 days (+5-day window). All subjects will complete clinical and pharmacodynamic assessments during each treatment period and PK blood samples will be collected prior to, during and after study medication administration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Lewy Body Dementia, Parkinson's Disease Rapid Eye Movement Sleep Behavior Disorder, Parkinson's Disease Dementia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Two 14-day periods, 2-way crossover design
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-Blind
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CST-103/CST-107 to Placebo
Arm Type
Experimental
Arm Description
Subjects will receive daily doses of CST-103 co-administered with CST-107 for 14 days, followed by a washout period of no drug for 14 days, followed by matching placebo for CST-103 and matching placebo for CST-107 for 14 days.
Arm Title
Placebo to CST-103/CST-107
Arm Type
Experimental
Arm Description
Subjects will receive daily doses of matching placebo for CST-103 co-administered with matching placebo for CST-107 for 14 days, followed by a washout period of no drug for 14 days, followed by daily doses of CST-103 co-administered with CST-107 for 14 days.
Intervention Type
Drug
Intervention Name(s)
CST-103, CST-107, matching placebo
Intervention Description
CST-103 and matching placebo orange capsules; CST-107 and matching placebo white capsules
Primary Outcome Measure Information:
Title
Change from Baseline in Negative Emotional Bias in the Facial Expression Recognition Task (FERT)
Description
Faces with six different basic emotions (happiness, fear, anger, disgust, sadness, surprise) are briefly displayed on a screen and participants are required to indicate the expression of the face via a button-press.
Time Frame
Days 1, 7, and 14 of each Treatment Period (Two 14-day periods)
Title
Change from Baseline in Cognitive Fluctuations
Description
Electroencephalogram (EEG), Activity Tracking, Pupil measurements, Dementia Cognitive Fluctuation Scale (DCFS)
Time Frame
Screening, Days 1 and 14 of each Treatment Period (Two 14-day periods)
Secondary Outcome Measure Information:
Title
Change from Baseline in CANTAB Cognitive Assessments
Description
Measures changes in cognition by testing psychomotor speed, attention, and memory via a touch tablet
Time Frame
Screening, Days 1, 7, 14 of each Treatment Period (Two 14-day periods)
Title
Digital wearable device (BioStamp)
Description
A wireless device that measures physical activity and sleep while at home
Time Frame
Screening, Days 1-14 of each Treatment Period (Two 14-day periods)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with RBD+PD: Male or female subjects ≥ 40 and ≤ 80 years of age, at time of informed consent. Diagnosed with Parkinson's Disease, as defined by the United Kingdom Parkinson Disease Brain Bank criteria, associated with REM sleep behavior disorder (RBD+PD) Modified Hoehn & Yahr ≥ stage 1 and ≤ stage 3 during "On" period as documented in the 3 months prior to Screening or completed at Screening. Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 28. Hospital Anxiety and Depression Scale (HADS) Depression Sub-score ≥ 8. Subjects with MCI: Male or female subjects ≥ 50 and ≤ 80 years of age, at time of informed consent. Meet the criteria for amnestic Mild Cognitive Impairment (MCI) as per the National Institute on Aging-Alzheimer's Association core clinical criteria. Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 26. No dementia according to the International Classifications of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Memory complaint reported by the subject or his/her partner, family member or caregiver. Score of greater than or equal to one standard deviation below age and educational norms in the Digit Symbol Substitution Test (DSST) during Screening. Cognitive decline not primarily caused by vascular, traumatic, or medical problems. HADS Depression Sub-score ≥ 8. Subjects with Dementia with Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD): Male or female subjects ≥ 50 and ≤ 80 years of age, at time of informed consent. Diagnosis of dementia associated with Dementia with Lewy Bodies or Parkinson's disease (PDD). Documented cognitive fluctuations endorsed on the Dementia Cognitive Fluctuation Scale (DCFS) with a combined score of ≥8 in items 4, 11, 12 and 14. Montreal Cognitive Assessment (MoCA) score ≥ 18 and ≤ 26. Have informant or caregiver throughout the study who will submit written consent to cooperate with this study, who routinely accompanies and/or 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. Modified Hoehn & Yahr ≥ stage 1 and ≤ stage 3 during "On" period as documented in the 3 months prior to Screening or completed at Screening. Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI. For ALL Subjects: 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. 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 reliable 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/m2, inclusive at Screening. Stable medical conditions for 3 months 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. Subjects who are unable to provide consent may use a Legally Authorized Representative. Exclusion Criteria: Poorly controlled hypertension despite lifestyle modifications and/or pharmacotherapy. Pulmonary disease, including asthma if requiring the use of a β2-Adrenergic bronchodilator, 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 frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, or Babinski sign. 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. Evidence of any significant clinical disorder or laboratory finding (or in the case of potassium levels below normal range) that renders the participant unsuitable for receiving an investigational drug. 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). Any clinically significant illness or disease as determined by medical and surgical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory assessments conducted at Screening. 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. Calculated creatinine clearance of ≤70 mL/min according to the Cockcroft-Gault equation. Current use of any prohibited prescription medication, over-the-counter medication, or herbal supplements/products. 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. Known or suspected alcohol or substance abuse within the past 12 months and/or positive test for alcohol or drugs of abuse. Active suicidal ideation within 3 months prior to study Screening. 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). Positive screening test for human immunodeficiency virus (HIV). Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Contraindications to wearing the BioStamp digital device sensors, which include but are not limited to implanted pacemakers, defibrillators, or other active implantable devices. Known allergies or hypersensitivities to adhesives or hydrogel. Other reasons for which the PI considers it is not in the best interest of the participant to undertake the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chief Medical Officer
Organizational Affiliation
CuraSen Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The University of Sydney
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2006
Country
Australia
Facility Name
Wesley Medical Research Ltd
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
QLD 4066
Country
Australia
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
NZBRI
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
MAC
City
Tankersley
State/Province
Barnsley
ZIP/Postal Code
S75 3DL
Country
United Kingdom
Facility Name
MAC
City
Blackpool
State/Province
Lancashire
ZIP/Postal Code
FY2 0JH
Country
United Kingdom
Facility Name
MAC
City
Manchester
ZIP/Postal Code
M13 9NQ
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Study of CST-103 Co-administered With CST-107 in Subjects With Neurodegenerative Disorders

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