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Trial registered on ANZCTR


Registration number
ACTRN12624000739516
Ethics application status
Approved
Date submitted
10/05/2024
Date registered
14/06/2024
Date last updated
14/06/2024
Date data sharing statement initially provided
14/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 study to evaluate the safety and pharmacokinetics of single and multiple doses of SION-719 in healthy participants
Scientific title
A Phase 1 randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses and multiple ascending doses of SION-719 in healthy participants
Secondary ID [1] 311966 0
SION-719-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 333569 0
Condition category
Condition code
Human Genetics and Inherited Disorders 330253 330253 0 0
Cystic fibrosis
Respiratory 330758 330758 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, randomised, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single ascending dose (SAD) and multiple ascending dose (MAD) of SION-719 in healthy participants. Study drug (SION-719 and placebo) will be administered as an oral suspension.
This study is comprised of 2 parts: Part A (SAD) and Part B (MAD). Each study part will include a Screening Period, a Treatment Period, and an End of Study (EoS) Telephone Contact.
Participants to be included in this study will be healthy male and female adults 18 to 55 years of age, inclusive, with no clinically significant concomitant medical conditions and who are not taking any concomitant medications.
All potential participants will be screened a maximum of 28 days (Day -28) prior to Check-in (Day -1) to assess their eligibility to enter the study and dosing will be initiated on Day 1. Participants will generally be fasted prior to each dose of study drug but some cohorts may be dosed fed at the discretion of the Sponsor and with confirmation by the Safety Review Committee (SRC).
Participants will be randomised 6:2 to active:placebo, and treatment assignments will be blinded.

SAD (Part A)
Participants in Part A of the study will be admitted to the Clinical Research Unit (CRU) on Day -1. On the following morning (Day 1), participants will receive a single dose of study drug (active or placebo depending on their randomised treatment assignment) in a fasted state (at least 10 hours pre-dose and 4 hours post-dose). Sentinel dosing will be employed for each Part A dose escalation cohort such that the first 2 participants will be enrolled and randomised 1:1 to active drug or placebo; if no stopping rules are met after 48 hours of monitoring, the remaining participants in the cohort will be randomised. Each cohort will enrol approximately 8 participants randomised 6:2 to active:placebo. Approximately 6 SAD cohorts are planned and dosing will begin at 20mg (Cohort 1) up to 160mg (Cohort 4). Dose levels for Cohorts 5 and 6 will be determined based on SRC review of safety and PK data from previous cohorts.

All participants will remain in the CRU until 72 hours following their final dose of study drug (Day 1) for safety monitoring and collection of blood samples for PK analysis. All participants will be contacted by phone for an EOS visit 7 (+/-1 day) after the last dose of study drug.

MAD (Part B)
Part B dosing will not begin until the SRC has reviewed the available safety data from at least the first 3 SAD cohorts and determines it is safe to proceed. A unique group of participants enrolled in Part B of the study will be admitted to the CRU on Day -1. Participants will receive a single dose level of study drug (active or placebo based on their randomised treatment assignment) administered twice daily (BID) for up to 10 days.
Participants will fast for at least 10 hours pre-dose and 4 hours post-dose for the first dose on Day 1 and for the last dose given on the morning of Day 10; for all other doses, participants will fast for at least 2 hours pre-dose and 2 hours post-dose.
Each cohort will enrol approximately 8 participants randomised 6:2 to active:placebo. The SRC may recommend lower or intermediate dose levels be explored, provided the selected dose or a higher dose has been declared safe and well tolerated in Part A. In addition, the SRC may recommend adjustment of the dosing frequency from BID based on the available safety and PK data. Approximately 6 MAD cohorts are planned, with dose escalation cohorts enrolled consecutively. Planned dose cohorts for the MAD part of the study will start at 20mg (Cohort 1), up to 160mg (Cohort 4). Dose levels for Cohorts 5 and 6 will be determined based on SRC review of safety and PK data from previous cohorts.

Participants will remain at the CRU for at least 72 hours following administration of their last dose (Day 13) for safety monitoring and collection of blood samples for PK analysis. All participants will be contacted by telephone for an EoS visit 7 (± 1) days after the last dose of study drug.

Clinical facility staff will administer the study drug only to participants included in this study following the procedures set out in the study protocol. Administration of study drugs will be recorded in the appropriate drug accountability records and the eCRF. Administration of study drug will be verified by a second staff member. Each participant will be given only the study drug preparation carrying his/her study number.
Intervention code [1] 328426 0
Treatment: Drugs
Comparator / control treatment
Placebo: SION-719 Placebo is composed of hypromellose
Control group
Placebo

Outcomes
Primary outcome [1] 338000 0
To assess the safety and tolerability of SION-719 when administered as single ascending oral doses in healthy participants
Timepoint [1] 338000 0
Adverse Events: AEs will be assessed continuously as they are reported or observed and reviewed daily at Screening, Day -1 (study check-in), Day 1, Day 2, Day 3, Day 4 (study check-out), Day 8 (End of Study) or Early Termination Visit (if applicable).

Vital Signs: the following will be assessed, blood pressure using a sphygmomanometer, heart rate and respiratory rate and temperature by thermometer. Assessed at Screening; at Day -1 (study check-in), Day 1, Day 2, Day 3, Day 4 (study check-out) and Early Termination Visit (if applicable).

Clinical Laboratory Evaluations: chemistry (includes liver function tests), haematology, coagulation study (screening only), and urinalysis. Blood draws and urine samples will be completed at Screening, Day -1, Day 1, Day 2, Day 3, Day 4 and Early Termination Visit (if applicable).

12-Lead ECG: ECG recordings will be obtained in triplicate at the following timepoints: Screening, Day -1 (study check-in), Day 1, Day 2, Day 3, Day 4 (study check-out) and Early Termination Visit (if applicable).

Physical Examinations: complete physical examination will be performed at Screening and Day -1 (study check-in). Subsequent physical examinations will be performed on Day 1, Day 2, Day 3, Day 4 (study check-out) and Early Termination Visit (if applicable) as clinically indicated to assess AEs.
Primary outcome [2] 338001 0
To assess the safety and tolerability of SION-719 when administered as multiple ascending oral doses in healthy participants
Timepoint [2] 338001 0
Adverse Events: AEs will be assessed continuously as they are reported or observed and reviewed at Screening, Day -1 (study check-in), Days 1 through 13 (study check-out), Day 17 (End of Study) or Early Termination Visit (if applicable) until resolution.

Vital Signs: the following will be assessed, blood pressure using a sphygmomanometer, heart rate and respiratory rate, and temperature by thermometer. Assessed at Screening; at Day -1 (study check-in), Days 1 through 13 (study check-out) and Early Termination Visit (if applicable).

Clinical Laboratory Evaluations: chemistry (includes liver function tests), haematology, coagulation study (screening only), and urinalysis. Blood draws and urine samples will be completed at Screening, Day -1 (study check-in), Days 1 through 13 (study check-out) and Early Termination Visit (if applicable).

12-Lead ECG: ECG recordings will be obtained in triplicate at the following timepoints: Screening, Day -1 (study check-in) , Days 1 through 13 (study check-out) and Early Termination Visit (if applicable).

Physical Examinations: complete physical examination will be performed at Screening and Day -1 (study check-in). Subsequent physical examinations will be performed on Days 1 through 13 (study check-out) and Early Termination Visit (if applicable) as clinically indicated to assess AEs.
Secondary outcome [1] 434075 0
To assess the single dose pharmacokinetics (PK) of SION-719 in healthy participants.
Timepoint [1] 434075 0
Plasma PK samples will be collected as follows:
Day 1, Day 2, Day 3, Day 4 and Early Termination Visit.
Secondary outcome [2] 434076 0
To assess the multiple dose pharmacokinetics (PK) of SION-719 in healthy participants.
Timepoint [2] 434076 0
Plasma samples for PK will be collected as follows:
Days 1, 2, 4, 6, 8, 10, 11, 12, 13 and Early Termination Visit (if applicable).
Secondary outcome [3] 435455 0
To assess the single dose potential metabolites of SION-719 in healthy participants.
Timepoint [3] 435455 0
Plasma samples for potential metabolites will be collected as follows:
Day 1, Day 2 and Early Termination Visit (if applicable).
Secondary outcome [4] 435458 0
To assess the multiple dose metabolites of SION-719 in healthy participants.
Timepoint [4] 435458 0
Plasma samples for potential metabolites will be collected as follows:
Days 1, 2, 4, 6, 8, 10, 11 and Early Termination Visit (if applicable).

Eligibility
Key inclusion criteria
Participants must meet all of the following criteria to be included in the study:
1. Healthy male or female adult participants aged 18 to 55 years, inclusive, at the time of consent.
2. Weight of at least 45 kg (99 lbs) and body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
3. Participant is willing to abstain from alcohol, caffeine, smoking, and nicotine-containing products for 72 hours prior to Day -1 through the duration of the study. Participant is willing to abstain from eating cruciferous vegetables, charcoal-grilled meats, and poppy seeds for 48 hours prior to dosing throughout the duration of the study
4. Participant has read, understood and voluntarily provided written informed consent
5. Participant has an understanding, ability, and willingness to fully comply with study procedures and restrictions.
6. Female participants (sex assigned at birth) must be of non-childbearing potential or willing to comply with acceptable highly effective contraceptive requirements (including negative pregnancy tests). Male participants (sex assigned at birth) must be infertile or willing to comply with acceptable highly effective contraceptive requirements.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants who meet any of the following criteria must be excluded from the study:
1. Participant has clinically significant current or recurrent illness, such as cardiovascular (including but not limited to known structural cardiac abnormalities, family history of long QT syndrome, or cardiac syncope or recurrent, idiopathic syncope), neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality which may affect safety or clinical laboratory evaluations.
2. Participant has a history of malignancy, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of recurrence for at least 3 years.
3. Participant has clinically significant abnormalities on ECG, physical examination, or vital sign assessment at Screening or Day -1.
4. Participant has any single reading of QTcF > 470 ms (females) or > 450 ms (males) at Screening or Day -1.
5. Chronic or habitual alcohol or tobacco use or use of recreational drugs in the opinion of the Investigator.
6. Participant is positive for drug screen at Screening or Day -1. Of note, the drug screen does not include cannabis, cotinine or alcohol testing at Screening but does include this testing at study Check-in (Day -1).
7. Participant has taken any prescription or over the counter medications within 14 days (or 5 half-lives of the medication, whichever is longer) prior to dosing or requires the use of these medications during the study, including herbal or homeopathic preparations (excluding standard doses of vitamin/mineral supplements and occasional acetaminophen or ibuprofen, which are allowed).
8. Participant has abnormalities at Screening or clinically significant abnormalities, in the opinion of the Investigator, at Day -1 on safety laboratory tests including serum chemistry, haematology, coagulation tests, and urinalysis.
a. Participant must have an estimated glomerular filtration rate >90 mL/min/1.73 m2 using the CKD-EPI 2021 formula and based on individual body surface area at Screening and Day -1.
b. Participant must have ALT, AST, alkaline phosphatase, and direct bilirubin less than or equal to the ULN at Screening and Day -1.
9. Participant has a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening.
10. Participant has a positive test for Coronavirus Disease 2019 (COVID-19) during the Screening Period (including Day -1).
11. Participant has used any medication listed on the Flockhart table that is a substrate, inhibitor, or inducer of CYP3A4, or a substrate of CYP1A2, CYP2B6, CYP2C8, CYP2C19 or CYP2D6 within 28 days or 10 half-lives (whichever is longer) prior to the planned first study drug administration. Additionally, participants must not have consumed other substances known to be potent inhibitors or inducers of CYPP450 such as Seville orange, grapefruit, or cranberry juice-containing products and herbal supplements such as St. John’s Wort within 14 days before the planned first study drug administration.
12. Participant has used any other prescription or over-the-counter medication that the Investigator judges is likely to interfere with the study or pose an additional risk in participating, within 14 days or 5 half-lives (whichever is longer), or has received any vaccinations within 14 days prior to the planned first study drug administration.
13. Participant has received an investigational product within 30 days or 5 half-lives (whichever is longer) of the first study drug administration or will start any other investigational product before the planned EoS Telephone Contact visit.
14. Participant has been treated with an investigational device within 30 days prior to first study drug administration or will start an investigational device study before the planned EoS Telephone Contact visit.
15. Participant has donated or lost greater than or equal to 400 mL blood (or plasma) within the last 6 weeks preceding the first study drug administration.
16. Participant has known or suspected intolerance or hypersensitivity to the investigational product, any closely related compound, or any of the stated ingredients.
17. Participant has an inability to follow a standardized meal schedule and diet or inability to fast, as required during 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)
Masking / blinding
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/06/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
96
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26414 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 42392 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 316310 0
Commercial sector/Industry
Name [1] 316310 0
Sionna Therapeutics, Inc
Country [1] 316310 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Sionna Therapeutics, Inc
Address
Country
United States of America
Secondary sponsor category [1] 318494 0
Commercial sector/Industry
Name [1] 318494 0
Avance Clinical Pty Ltd
Address [1] 318494 0
Country [1] 318494 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315126 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315126 0
https://www.alfredhealth.org.au/research/ethics-research-governance
Ethics committee country [1] 315126 0
Australia
Date submitted for ethics approval [1] 315126 0
08/05/2024
Approval date [1] 315126 0
05/06/2024
Ethics approval number [1] 315126 0

Summary
Brief summary
This is a Phase 1, first-in-human (FIH), randomised, double-blind, placebo controlled study to evaluate the safety, tolerability, and pharmacokinetics (PK) of single ascending doses (SAD) and multiple ascending doses (MAD) of SION-719 administered as an oral suspension in healthy participants.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133746 0
Dr Gloria Wong
Address 133746 0
Nucleus Network Brisbane, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 133746 0
Australia
Phone 133746 0
+61737072720
Fax 133746 0
Email 133746 0
g.wong@nucleusnetwork.com.au
Contact person for public queries
Name 133747 0
Gloria Wong
Address 133747 0
Nucleus Network Brisbane, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 133747 0
Australia
Phone 133747 0
+61 1800243733
Fax 133747 0
Email 133747 0
g.wong@nucleusnetwork.com.au
Contact person for scientific queries
Name 133748 0
Gloria Wong
Address 133748 0
Nucleus Network Brisbane, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 133748 0
Australia
Phone 133748 0
+61 1800243733
Fax 133748 0
Email 133748 0
g.wong@nucleusnetwork.com.au

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.