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Trial registered on ANZCTR


Registration number
ACTRN12620000671965
Ethics application status
Approved
Date submitted
11/03/2020
Date registered
12/06/2020
Date last updated
12/06/2020
Date data sharing statement initially provided
12/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An open-label study of combination therapy of CNSA-001 with levodopa in patients with Parkinson's Disease for the treatment of motor and non-motor symptoms of Parkinson's Disease.
Scientific title
A Phase 2a Open-Label Study of CNSA-001 in Patients with Parkinson’s Disease
Secondary ID [1] 300309 0
PDS-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease 315912 0
Condition category
Condition code
Neurological 314184 314184 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 2 open-label study to assess the safety and tolerability of oral doses of 60 mg/kg CNSA-001 in patients with Parkinson's Disease who may need additional therapy to levodopa.

Eligible patients will take CNSA-001 daily with food for 14 days. Patients will be given a dosing diary to record all doses taken at home. Patients will also be asked to return all used dosing bottles to confirm compliance.

Following the completion of dosing, three follow-up visits will be conducted by phone on 1-3 days after the last dose, 7-10 days after the last dose, and 30 days after the last dose.
Intervention code [1] 316612 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322608 0
The primary objective is to assess the safety and tolerability of multiple oral daily doses of CNSA-001 60 mg/kg with food
Timepoint [1] 322608 0
Vital signs, physical examinations, and adverse events will be collected at Screening, Day 1, Day 2, and Day 14. Adverse events will be monitored as well on each of the phone follow-up visits.

Clinical safety laboratory tests will be collected at Screening, Day 1, and Day 14.
Secondary outcome [1] 379034 0
To assess changes from baseline of homovanillic acid (HVA) in cerebrospinal fluid (CSF) after multiple oral doses of CNSA-001.
Timepoint [1] 379034 0
A lumbar puncture for the collection of CSF will be performed pre-dose on Day 1 and 3-4 hours post-dose on Day 14.
Secondary outcome [2] 379035 0
To measure the pharmacokinetics (PK) of CNSA-001 and BH4 in patients with Parkinson's Disease following the administration of CNSA-001. PK parameters at a minimumn will include AUC, Cmax, Tmax, t1/2, and Ke.
Timepoint [2] 379035 0
Blood samples for PK analysis will be collected at the following timepoints of the treatment period:
Day 1 - Within 30 minutes before dosing or simultaneously with the lumbar puncture and 0.5 hr, 1 hr, 2 hr, 4 hr, and 8 hr post-dose
Day 2 - prior to the administration of the Day 2 dose
Day 14 - immediately before or simultaneously with lumbar puncture
Secondary outcome [3] 379036 0
The evaluate changes from baseline and Day 14 in Total Daily OFF Time after CNSA-001 treatment
Timepoint [3] 379036 0
Patients will be asked to complete a 3-day diary during Screening and each week of treatment and record occurrences of OFF time
Secondary outcome [4] 379038 0
To evaluate the effect of CNSA-001 on the improvement of movement disorders after the administration of multiple oral doses of CNSA-001.
Timepoint [4] 379038 0
Patients will complete the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale MDS-UPDRS at Screening, Day 1 pre-dose, and Day 14 of the treatment period.
Secondary outcome [5] 379039 0
To evaluate the effect of CNSA-001 as a change from baseline in serotonin after the administration of multiple oral doses of CNSA-001
Timepoint [5] 379039 0
Blood samples for serotonin will be collected at Screening, Day 1, and Day 14 of the treatment period
Secondary outcome [6] 381623 0
To assess changes from baseline in BH4 and sepiapterin measured in plasma after multiple oral doses of CNSA-001
Timepoint [6] 381623 0
Blood samples for BH4 and sepiapterin measurements will be collected at the same time, or immediately before, the CSF collection at pre-dose on Day 1 and 3-4 hours post-dose on Day 14.
Secondary outcome [7] 381624 0
To evaluate the effect of CNSA-001 as a change from baseline in dopamine after the administration of multiple oral doses of CNSA-001
Timepoint [7] 381624 0
Blood samples for dopamine will be collected at Screening, Day 1, and Day 14 of the treatment period
Secondary outcome [8] 383674 0
To assess changes from baseline of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) after multiple oral doses of CNSA-001.
Timepoint [8] 383674 0
A lumbar puncture for the collection of CSF will be performed pre-dose on Day 1 and 3-4 hours post-dose on Day 14.
Secondary outcome [9] 383675 0
To assess changes from baseline of tetrahydrobiopterin (BH4) in cerebrospinal fluid (CSF) after multiple oral doses of CNSA-001.
Timepoint [9] 383675 0
A lumbar puncture for the collection of CSF will be performed pre-dose on Day 1 and 3-4 hours post-dose on Day 14.
Secondary outcome [10] 383676 0
To assess changes from baseline of dihydrobiopterin (BH2) in cerebrospinal fluid (CSF) after multiple oral doses of CNSA-001.
Timepoint [10] 383676 0
A lumbar puncture for the collection of CSF will be performed pre-dose on Day 1 and 3-4 hours post-dose on Day 14.
Secondary outcome [11] 383677 0
To assess changes from baseline of sepiapterin in cerebrospinal fluid (CSF) after multiple oral doses of CNSA-001.
Timepoint [11] 383677 0
A lumbar puncture for the collection of CSF will be performed pre-dose on Day 1 and 3-4 hours post-dose on Day 14.
Secondary outcome [12] 383678 0
To assess changes from baseline of neopterin in cerebrospinal fluid (CSF) after multiple oral doses of CNSA-001.
Timepoint [12] 383678 0
A lumbar puncture for the collection of CSF will be performed pre-dose on Day 1 and 3-4 hours post-dose on Day 14.

Eligibility
Key inclusion criteria
Key inclusion criteria include:
1. Confirmed diagnosis of Parkinson’s Disease
2. Males and females greater than or equal to 18 years
3. Females must be either postmenopausal for at least 1 year, or surgically sterile for at least 6 months or, if of childbearing potential and not abstinent, willing to use a combination method of contraception from screening through 30 days after the last dose of study drug
4. Males (if sexually active and nonsterile) with female partners of childbearing potential must agree to use barrier contraceptive with spermicidal foam from screening through 90 days after the last dose of study drug.
5. The patient is clinically stable on therapy for management of Parkinson’s Disease, on a stable dose of levodopa or dopamine replacement equivalent medication, but needs more levodopa or dopamine replacement equivalent to control disease.
6. The patient is willing to refrain from tobacco use
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Key exclusion criteria include:
1. Weight > 110 kg
2. Diagnosis of functional (psychogenic) movement disorders
3. Significant chronic medical illness other than Parkinson’s Disease
4. Gastrointestinal disease that could affect absorption of the study drug
5. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy
6. Inability to tolerate oral medication
7. Any medical condition or history that would prohibit the patient from completing a MRI
8. History of surgical intervention for Parkinson’s Disease
9. Currently taking an antifolate including, but not limited to, methotrexate, pemetrexed, or trimetrexate



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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Data from approximately 6 patients will be used for the statistical analysis of this study.

Four study populations will be used to summarize data:
• The safety population defined as all patients who received any amount of study drug. All safety summaries will be conducted in this population.
• The PD population defined as all patients who enroll, receive any amount of study drug, with an available baseline CSF sample and 1 post Treatment CSF sample. All PD analyses will be conducted in this population.
• The efficacy population defined as all patients who enroll, receive any amount of study drug, have an available baseline and at least 1 post-Treatment Day 1 efficacy assessment. All efficacy analyses will be conducted in this population.
• The PK population is defined as all subject who received at least 1 dose of study drug and had at least 1 blood sample collected for analysis of CNSA-001 or BH4 concentrations.

Enrollment, protocol deviations, demographics (age, sex, race/ethnicity), and medical history will be summarized with descriptive statistic in the safety, PD, and efficacy populations. All efficacy and PD parameters will also be summarized with summary statistics

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 15677 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 29096 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304730 0
Commercial sector/Industry
Name [1] 304730 0
Censa Pharmaceuticals Australia Pty Ltd
Address [1] 304730 0
Floor 19, HWT Tower
40 City Road
Southbank, VIC 3006

Country [1] 304730 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Censa Pharmaceuticals Australia Pty Ltd
Address
Floor 19, HWT Tower
40 City Road
Southbank, VIC 3006

Country
Australia
Secondary sponsor category [1] 305045 0
Commercial sector/Industry
Name [1] 305045 0
InClin Pty Ltd
Address [1] 305045 0
25 Berry Street, Suite 210,
North Sydney, NSW, 2060
Country [1] 305045 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305154 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 305154 0
North Terrace
Adelaide, SA, 5000
Ethics committee country [1] 305154 0
Australia
Date submitted for ethics approval [1] 305154 0
30/08/2019
Approval date [1] 305154 0
06/01/2020
Ethics approval number [1] 305154 0

Summary
Brief summary
This is a single-site phase 2 open-label study to assess the effects of CNSA-001 in patients with Parkinson’s Disease who need adjunctive treatment in combination with levodopa. The study will enroll approximately 6 patients.

The total study duration is up to 65 days, which includes a 21-day screening window, 14 days of treatment with CNSA-001 and a 30-day follow up period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99422 0
Prof Guy Ludbrook
Address 99422 0
Level 4G.1 East, Royal Adelaide Hospital,
Port Road, Adelaide,
South Australia, Australia 5000.
Country 99422 0
Australia
Phone 99422 0
+61 08 7074 1544
Fax 99422 0
Email 99422 0
Guy.Ludbrook@sa.gov.au
Contact person for public queries
Name 99423 0
Mr Taylor Kilfoil
Address 99423 0
InClin Pty Ltd
25 Berry Street, Suite 210
North Sydney, NSW 2060
Australia
Country 99423 0
Australia
Phone 99423 0
+61 408 880 403
Fax 99423 0
Email 99423 0
taylorkilfoil@inclin.com
Contact person for scientific queries
Name 99424 0
Mr Neil Smith
Address 99424 0
Censa Pharmaceuticals Australia Pty Ltd
Floor 19, HWT Tower,
40 City Road, Southbank,
VICTORIA, 3006
Country 99424 0
Australia
Phone 99424 0
+1 317 443 2706
Fax 99424 0
Email 99424 0
nsmith@censapharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data to remain confidential
What supporting documents are/will be available?
No other documents available
Summary results
No Results