Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001117606
Ethics application status
Approved
Date submitted
21/09/2023
Date registered
27/10/2023
Date last updated
27/10/2023
Date data sharing statement initially provided
27/10/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1 single and multiple ascending dose study of YA-101 in Healthy Subjects
Scientific title
A Double-Blind, Placebo-Controlled, Single Dose and Multiple Ascending Dose, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of YA-101 in Healthy Subjects
Secondary ID [1] 310597 0
YA-101-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple System Atrophy
 331473 0
Condition category
Condition code
Neurological 328200 328200 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase 1 study consisting of Part 1~Part 2. Besides the one food effect (FE) cohort, each cohort in Part 1~Part 2 is randomized, placebo-controlled, double-blinded to establish safety and tolerability in healthy volunteers (HV) following single ascending dose (SAD) and multiple ascending dose (MAD). FE is a single cohort, cross-over, 2-period study planned to evaluate the effect of food on the PK profile of open-label YA-101.

- Part 1 will assess the safety, tolerability, and PK of YA-101 administered to healthy adult volunteers as a single-ascending dose (HV SAD)
- Part 2 will assess the safety, tolerability, and PK of YA-101 administered to healthy adult volunteers as multiple-ascending doses (HV MAD), and as a single dose administered with and without food to assess food effect (HV FE).

Investigational Product: YA-101
Dose form: Suspension
Route of Administration: Oral
Dose (mg/day): Starting dose for HV SAD Cohort 1 is based on the human equivalent dose (HED) calculated from the NOAEL reported in the 28-day GLP rat toxicity study, with application of an appropriate safety factor.

SAD: Starting dose for Cohort 1 is starting at 900mg and escalating to a maximum of 9600mg of YA-101.
Subsequent dose levels for Cohort 2 and Cohort 3 will be determined based on the emerging safety, tolerability, and PK data in the preceding cohort(s).Dose frequency: once per day

FE: HV FE doses will be determined based on the emerging safety, tolerability, and PK data from SAD cohorts. In the fed state, a high-fat (approximately 50% of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal is provided before dosing. YA-101 suspension will be administered within 30 minutes after the completion of meal. (Dose frequency: once per day on Day 1 and Day 4)

MAD: HV MAD doses will be determined based on the emerging safety, tolerability, and PK data from SAD cohorts. The dosing time of Part 1 is separated from the first dosing time of Part 2 by greater than 1 week. Participants from Part 1 may also participate in Part 2.

Dose frequency: twice daily for 14 days. On Day 14, subjects will only take the morning dose.

Placebo: YA-101 matching placebo will be provided for each cohort in SAD and MAD.

Study drug administration will take place on-site with oversight by study staff. Furthermore, the study drug must be dispensed under the supervision of the investigator or an authorized designee, and it should be dispensed exclusively to study subjects. The designated site staff or pharmacist will maintain records of the study drug received, dispensed to subjects, and any returned quantities.
Intervention code [1] 327006 0
Treatment: Drugs
Comparator / control treatment
Placebo: The placebo is a powder mixed with liquid, having the same concentration and suspension dosage form as YA-101, and is stored at 2-8 degrees Celsius.
Route of administration: Oral.

FE: In the fasted state, the comparator group for the food effect cohort, following an overnight fast of at least 10 hours, subjects will be administered YA-101 suspension.
Control group
Placebo

Outcomes
Primary outcome [1] 336077 0
To evaluate the safety and tolerability of YA-101 following single ascending oral administration in healthy volunteers.

These will be assesed by monitoring-
-Incidence and severity of AES - AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product) by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events (CTCAE) (V5.0) as 5 grades.

-Changes in clinical laboratory parameters including blood tests for hematology, blood biochemistry and coagulation; using urine sample for urinaurinalysis

-Changes in the elctrocardiogram (ECG) findings

-Change in vital signs measurements. Vital signs will include mesurement of heart rate, respiration rate, systolic and diastolic blood pressure, and oral temperature using EarlyVue VS30 or Vital Signs Monitor 53NTO devices.
Timepoint [1] 336077 0
Adverse Events (AEs) and Serious Adverse events (SAEs) : SAD- Screening, Day -1, Day 1, Day 2, and Day 8 post last dose administration;

Safety Laboratory assessments: SAD- Screening, Day -1, Day 1, Day 2, and Day 8 (±2) post last dose administration or Early Termination (ET);

ECG: SAD- Screening, Day -1, Day 1, Day 2, and Day 8 (±2) post last dose administration or ET;

Vital Signs: SAD- Screening, Day -1, Day 1, Day 2, and Day 8 (±2) post last dose administration or ET;

Primary outcome [2] 336090 0
To evaluate the effect of food on the PK profile of YA-101 following a single dose of YA-101 in healthy volunteers in fed and fasted states determined by the changes in the plasma and urine PK parameters.

Plasma parameters tthat will be assesses include Tmax(time to reach maximum plasma concentration), Cmax (mamximum plasma concentration), and AUC0-last (Area under curve from 0 to last measurable concentration).
Urine PK parameter include cumulative amount of drug excreted in urine (Ae), percent fraction of drug recovered in urine (Fe) and renal clearance (CLr)
Timepoint [2] 336090 0
Plasma PK samples to be collected at the following time points: pre-dose Day 1, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours Day 1 post-dose. Day 2 collection is the 24 hours post Day 1 collection for PK. PK samples will also be collected at pre-dose Day 4, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours Day 4 post-dose. Day 5 collection is the 24 hours post Day 4 collection for PK.

PK urine collection: will be collected on Day 1 and Day 4 pre-dose at (-6 to 0 hours), and at (0-6), (6-12), (12-24) hour intervals post-dose.
Primary outcome [3] 336280 0
To evaluate the safety and tolerability of YA-101 following multiple ascending oral administration in healthy volunteers.

These will be assesed by monitoring-
-Incidence and severity of AES - AEs and SAEs will be assessed for severity and causality (relationship of the event to the investigational product) by the study investigator using the specified grading definitions Common Terminology Criteria for Adverse Events (CTCAE) (V5.0) as 5 grades.

-Changes in clinical laboratory parameters including blood tests for hematology, blood biochemistry and coagulation; using urine sample for urinaurinalysis

-Changes in the elctrocardiogram (ECG) findings

-Change in vital signs measurements. Vital signs will include mesurement of heart rate, respiration rate, systolic and diastolic blood pressure, and oral temperature using EarlyVue VS30 or Vital Signs Monitor 53NTO devices.
Timepoint [3] 336280 0
Adverse Events (AEs) and Serious Adverse events (SAEs) : MAD- Screening, Day -1, Days 1 to 15, and Day 21 post first-dose administration.

Safety Laboratory assessments: MAD- Screening, Day -1, Days 1 to 15, and Day 21 post first-dose administration.

ECG: MAD- Screening, Day -1, Days 1 to 15, and Day 21 (±2) post first-dose administration or ET.

Vital Signs: MAD- Screening, Day -1, Days 1 to 15, and Day 21 (±2) post first-dose administration or ET.
Secondary outcome [1] 426816 0
Characterize the pharmacokinetic (PK) prole of YA-01 in healthy participants after single ascending doses with urine and plasma samples.
Plasma parameters which will be assessed include - t1/2 (apparent terminal half-life ), Tmax (time to reach maximum plasma concentration), Cmax (mamximum plasma concentration), and AUC0-last (Area under curve from 0 to last measurable concentration)

Urine PK parameters including, but not limited to, cumulative amount of drug excreted in urine (Ae), percent fraction of drug recovered in urine (Fe) and renal clearance (CLr) will be assessed.
Timepoint [1] 426816 0
For the SAD cohorts-
-Blood samples for PK analyses will be collected at pre-dose, and at 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose. Day 2 collection is the 24 hours post Day 1 collection for PK.
-urine sample will be collected on Day 1 pre-dose at (-6 to 0 hours), and at (0-6), (6-12), (12-24) hour intervals post-dose.
Secondary outcome [2] 427629 0
Characterize the pharmacokinetic (PK) prole of YA-01 in healthy participants after multiple ascending doses with urine and plasma samples.
Plasma parameters which will be assessed include - t1/2 (apparent terminal half-life ), Tmax (time to reach maximum plasma concentration), Cmax (mamximum plasma concentration), and AUC0-last (Area under curve from 0 to last measurable concentration)

Urine PK parameters including, but not limited to, cumulative amount of drug excreted in urine (Ae), percent fraction of drug recovered in urine (Fe) and renal clearance (CLr) will be assessed.
Timepoint [2] 427629 0
For MAD cohorts-
-Blood samples for PK analyses will be collected on Day 1, Day 3, Day 7: pre-dose, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 after the morning dose, and pre-dose.  Day 14: pre-dose, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours after the morning dose. Day 15: 24 hours after the morning dose on Day 14.;  Days 2,4-6, 8-13: pre-dose.
-Urine samples will be collected on Day 1 pre-dose at (-6 to 0 hours), and at (0-6), (6-12) hour intervals post-dose of morning dose and at (0-12) hours post-dose of evening dose. Urine samples will also be collected on Day 7 and Day 14 at (0-6), (6-12) hour intervals post-dose of morning dose and on Day 7 at (0-12) hours post-dose of evening dose.

Eligibility
Key inclusion criteria
1. Subjects 18 to 65 years of age (inclusive) and in good state of health.
2. Must be able to communicate and participate in the whole study.
3. Must provide written informed consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subject who has received any investigational drug, stem cell therapy, or inactivated/live vaccinations within 30 days.
2. Subject who is an employee or immediate family member of the Sponsor or the study site.
3. History of drug, alcohol, or smoking abuse in the past 2 years prior to screening.
4. Tested positive for drug abuse.
5. Unwilling to refrain from the use of any prescription medications.
6. Subject not suitable for multiple venipunctures.
7. Has clinically significant abnormal clinical chemistry, hematology, urinalysis, or tested positive for hepatitis B virus, hepatitis C virus, or human immunodeficiency virus at screening.
8. Has clinical history or evidence of allergic, hematological, endocrine, cardiovascular, renal, hepatic, pulmonary, gastrointestinal, neurological, psychiatric disease, or malignancy.
9. Any other condition which is deemed unsuitable for participating in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
12/10/2023
Date of last participant enrolment
Anticipated
15/01/2024
Actual
Date of last data collection
Anticipated
9/02/2024
Actual
Sample size
Target
60
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25525 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 41346 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 314810 0
Commercial sector/Industry
Name [1] 314810 0
Yoda Pharmaceuticals Aus Pty Ltd
Country [1] 314810 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Yoda Pharmaceuticals Aus Pty Ltd
Address
Level 7, 330 Collins Street, Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 316798 0
None
Name [1] 316798 0
Address [1] 316798 0
Country [1] 316798 0
Other collaborator category [1] 282810 0
Commercial sector/Industry
Name [1] 282810 0
Novotech(Australia) Pty Limited
Address [1] 282810 0
Level 19, 66 Goulburn Street, Sydney NSW 2000, Australia
Country [1] 282810 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313816 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 313816 0
Ethics committee country [1] 313816 0
Australia
Date submitted for ethics approval [1] 313816 0
02/08/2023
Approval date [1] 313816 0
26/09/2023
Ethics approval number [1] 313816 0
2023-07-903

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129434 0
Prof Sam Salman
Address 129434 0
Sir Charles Gairdner Hospital, B-Block, Hospital Avenue, Nedlands WA 6009
Country 129434 0
Australia
Phone 129434 0
+61 8 6382 5100
Fax 129434 0
Email 129434 0
[email protected]
Contact person for public queries
Name 129435 0
Jane Tseng
Address 129435 0
Yoda Therapeutics Inc., 4F-4, No. 305, Sec. 3, Zhongxiao E. Rd., Da' an Dist., Taipei City 106452, Taiwan, R.O.C.
Country 129435 0
Taiwan, Province Of China
Phone 129435 0
+1 857 468 9328
Fax 129435 0
Email 129435 0
[email protected]
Contact person for scientific queries
Name 129436 0
Jane Tseng
Address 129436 0
Yoda Therapeutics Inc., 4F-4, No. 305, Sec. 3, Zhongxiao E. Rd., Da' an Dist., Taipei City 106452, Taiwan, R.O.C.
Country 129436 0
Taiwan, Province Of China
Phone 129436 0
+1 857 468 9328
Fax 129436 0
Email 129436 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.