Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000467134
Ethics application status
Approved
Date submitted
14/03/2019
Date registered
20/03/2019
Date last updated
2/04/2019
Date data sharing statement initially provided
20/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An Imaging Study to Determine Changes in Brain Glucose Metabolism and Cerebral Blood Flow after Single-Dose of CST-101 in Healthy Subjects and Patients with Mild Cognitive Impairment
Scientific title
An Open-Label, Brain Imaging Study Using Positron Emission Tomography with 18F-FDG and MRI with Arterial Spin Labeling to Determine Changes in Brain Glucose Metabolism and Cerebral Blood Flow after Single-Dose Intravenous Administration of CST-101 in Healthy Subjects and Patients with Mild Cognitive Impairment
Secondary ID [1] 297672 0
None
Universal Trial Number (UTN)
U1111-1227-9693
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 311948 0
Condition category
Condition code
Neurological 310529 310529 0 0
Studies of the normal brain and nervous system
Neurological 310638 310638 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Interventions include the following:
Arm 1 - single-dose intravenous administration of 300 µg CST-101
Arm 2 - single-dose intravenous administration of 900 µg CST-101
Arm 3 - single-dose intravenous administration of 1800 µg CST-101
Arm 4 - single-dose intravenous administration of 1800 µg CST-101 with 40 mg CST-107 oral tablet
Arm 5 - single-dose intravenous administration of 2400 µg CST-101 with 80 mg CST-107 oral tablet

CST-101 and CST-107 will be administered at the clinic.

The first group of 4 healthy volunteers (cohort 1) will receive treatment arms 1 and 2.

The second group of 4 healthy volunteers (cohort 2) will receive treatment arms 3 and 4.

The third group of 4 healthy volunteers (cohort 3) will receive treatment arm 5.

The fourth group of 4 patients with Mild Cognitive Impairment (cohort 4) will receive treatment arm 5.
Intervention code [1] 313906 0
Treatment: Drugs
Comparator / control treatment
Multiple treatment arms in the healthy volunteers will be compared with the treatment arm in patients with mild cognitive impairment
Control group
Active

Outcomes
Primary outcome [1] 319387 0
Change in cerebral blood flow in pre-specified ROI (frontal cortex) as measured by Arterial Spin Labeling (ASL) MRI scan after CST-101 IV administration in healthy subjects
Timepoint [1] 319387 0
Day 1 and Day 3
Primary outcome [2] 319388 0
Change in regional metabolism at specified regions of interest (ROI) (frontal cortex), as reflected by Arterial Spin Labeling (ASL) MRI scan after CST-101 IV administration in MCI patients
Timepoint [2] 319388 0
Day 3
Primary outcome [3] 319485 0
Change in regional metabolism at specified regions of interest (ROI) (frontal cortex), as reflected by 18F-FDG PET after CST-101 IV administration in MCI patients
Timepoint [3] 319485 0
Day 3
Secondary outcome [1] 367996 0
Change in the brain % resting state network strength as measured by blood oxygenation level dependent (BOLD) MRI, after CST-101 IV administration in healthy subjects
Timepoint [1] 367996 0
Day 1 and Day 3
Secondary outcome [2] 367997 0
Adverse events (AE), electrocardiograms (ECGs), vital signs, laboratory safety tests (hematology, chemistry and urinalysis) in healthy subjects and MCI patients
Timepoint [2] 367997 0
Days 1 through Day 3
Secondary outcome [3] 367998 0
Change in brain 18F-FDG PET signal in pre-specified ROI (frontal cortex) after CST-107 by mouth administration
Timepoint [3] 367998 0
Day 3
Secondary outcome [4] 367999 0
Effects of CST-101 on heart rate (using ambulatory blood pressure monitoring device) in the absence or presence of CST-107 PO in healthy subjects and MCI patients
Timepoint [4] 367999 0
Day 3
Secondary outcome [5] 368000 0
Change in brain 18F-FDG PET signal in pre-specified ROI (frontal cortex) after CST-101 intravenous administration in patients with MCI
Timepoint [5] 368000 0
Day 3
Secondary outcome [6] 368380 0
Change in brain ASL MRI signal in pre-specified ROI (frontal cortex) after CST-107 by mouth administration
Timepoint [6] 368380 0
Day 3
Secondary outcome [7] 368387 0
Effects of CST-101 on blood pressure (using ambulatory blood pressure monitoring device) in the absence or presence of CST-107 by mouth administration in healthy subjects and MCI patients
Timepoint [7] 368387 0
Day 3

Eligibility
Key inclusion criteria
Healthy subject volunteers must meet the following:
- Male aged 18-70 years
- Free from clinical significantly illness or disease
- No current use of any prescription medications, over-the-counter medications or nutritional supplements.

MCI patients must meet the following:
- Male or female aged 50-75 years
- Women of child-bearing potential must agree to effective methods of birth control
- Meet the criteria for amnestic MCI, as per the National Institute on Aging-Alzheimer's Association core clinical criteria
- Mini-Mental Status Exam (MMSE) Score greater than or equal to 26
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All subjects must not meet the following:
- History of any clinically significant disease or illness
- Clinically significant laboratory or ECG abnormality.
- Positive screening test for human immunodeficiency virus (HIV).
- Positive screening test for hepatitis C antibody (HCV Ab) or current hepatitis B infection.
- History of drug or alcohol abuse >12 months prior to Screening.
- History of nicotine use >6 months.
- A positive test for drugs of abuse or alcohol
- Contraindications for MRI and/or PET scans.

Other exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Sequential cohort enrollment with increasing doses of CST-101.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
No formal sample size estimation was performed; the sample size is based on practical considerations and is standard for these types of studies.

Statistical summaries will be descriptive in nature (e.g., means, standard deviations, and percentiles).

Safety outcomes will be listed and summarized descriptively by treatment arm, as applicable. All reported adverse events will be coded to system organ class (SOC) and preferred term (PT), using MedDRA®. Laboratory data will be listed, with values outside of normal ranges identified.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/04/2019
Actual
Date of last participant enrolment
Anticipated
28/06/2019
Actual
Date of last data collection
Anticipated
12/07/2019
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment outside Australia
Country [1] 21338 0
New Zealand
State/province [1] 21338 0
Christchurch

Funding & Sponsors
Funding source category [1] 302200 0
Commercial sector/Industry
Name [1] 302200 0
CuraSen Therapeutics, Inc.
Country [1] 302200 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
CuraSen Therapeutics, Inc.
Address
2655 Campus Drive, Suite 110
San Mateo, California 94403
Country
United States of America
Secondary sponsor category [1] 302043 0
Commercial sector/Industry
Name [1] 302043 0
Illingworth Research Group Limited
Address [1] 302043 0
St George’s House
1 St George’s Street
Macclesfield
Cheshire, SK11 6TG
Country [1] 302043 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302879 0
Health and Disability Ethics Committees
Ethics committee address [1] 302879 0
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 302879 0
New Zealand
Date submitted for ethics approval [1] 302879 0
14/02/2019
Approval date [1] 302879 0
11/03/2019
Ethics approval number [1] 302879 0
19/CEN/20

Summary
Brief summary
This is an open-label study using 18F-FDG PET and MRI scans to evaluate cerebral metabolic activity, after single-dose intravenous administration of CST-101 in healthy adult subjects and patients with MCI.

Four cohorts are planned for this study, and approximately 4 subjects will be enrolled per cohort following study eligibility confirmation during the screening period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91710 0
Dr Chris Wynn
Address 91710 0
Christchurch Clinical Studies Trust Ltd
Level 4, 265 Antigua Street,
Christchurch 8011
Country 91710 0
New Zealand
Phone 91710 0
+64 3 3729477
Fax 91710 0
Email 91710 0
[email protected]
Contact person for public queries
Name 91711 0
Dr Chris Wynn
Address 91711 0
Christchurch Clinical Studies Trust Ltd
Level 4, 265 Antigua Street,
Christchurch 8011
Country 91711 0
New Zealand
Phone 91711 0
+64 3 3729477
Fax 91711 0
Email 91711 0
[email protected]
Contact person for scientific queries
Name 91712 0
Dr Chris Wynn
Address 91712 0
Christchurch Clinical Studies Trust Ltd
Level 4, 265 Antigua Street,
Christchurch 8011
Country 91712 0
New Zealand
Phone 91712 0
+64 3 3729477
Fax 91712 0
Email 91712 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.