Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624001220550
Ethics application status
Approved
Date submitted
11/09/2024
Date registered
4/10/2024
Date last updated
4/10/2024
Date data sharing statement initially provided
4/10/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of SION-719 in healthy participants - Part C
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 - Part C
Secondary ID [1] 312794 0
SION-719-101
Universal Trial Number (UTN)
Trial acronym
Linked study record
Parts A & B are listed on previously registered trial ACTRN12624000739516

Health condition
Health condition(s) or problem(s) studied:
Cystic fibrosis 334855 0
Condition category
Condition code
Human Genetics and Inherited Disorders 331409 331409 0 0
Cystic fibrosis
Respiratory 331767 331767 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, open-label study designed to evaluate the effect of food on the pharmacokinetics (PK) of SION-719, and the bioequivalence of a solid oral formulation compared with oral suspension formulation in healthy participants.

This study will include a Screening Period, a Treatment Period, and an End of Study (EoS) phone call. 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, This study will be open label.

Participants will be admitted to the Clinical Research Unit (CRU) on Day -1. On Day -1 or Day 1, each participant will be randomised to 1 of 3 open-label SION-719 treatment sequences (each consisting of 3 separate dose periods that will be given in a pre-specified order) and will receive the first dose of SION-719 in Period 1, dose to be determined (TBD); a dose will be selected at or below a dose that has been safe and well tolerated in the prior single ascending dose (SAD) study part (not exceeding 160 mg). Following a washout period of approximately 72 hours (actual duration will be determined prior to the start of this study, participants will receive the second dose of SION-719 in Period 2 of the sequence (Day 5). Following a washout period of approximately 72 hours (actual duration will be determined prior to the start of this study), participants will receive the third dose of SION-719 in Period 3 of the sequence (Day 9). The washout period between doses may be extended based on emerging PK data, in which case the day of dosing in Period 2 and Period 3 will be adjusted accordingly. Approximately 8 to 12 participants per cohort will be enrolled in this study. It may include up to 2 cohorts at 2 dose levels using doses equal to or less than doses that have been tested (in the prior SAD study) and found to be safe and well tolerated. In each dose period participants will receive one of the following treatments: Treatment I a single oral dose of SION-719 given as a tablet under fasted conditions. Treatment II a single oral dose of SION-719 given as a suspension under fasted conditions (as above) and Treatment III. a single oral dose of SION-719 given as a tablet dosed 30 minutes after the start of a standardised high-fat meal.
For the fasted dosing in Treatment I and II participants will be fasted for at least 10 hours pre-dose and 4 hours post-dose (if dose 1), or for 2 hours pre-dose and 2 hours post dose (if subsequent dose) depending on the treatment sequence. In Treatment III the high fat meal will consist of the following with no substitutions:
o 2 eggs fried in butter
o 2 strips of bacon
o 2 slices of toast with butter
o 227 grams of hash brown potatoes
o 236 mls of whole milk
Participants need to consume at least 75% of the high fat meal.

Participants will remain at the CRU for at least 72 hours following administration of their last dose (Day 9) for safety monitoring and collection of blood samples for PK analysis. The duration of participant follow up may be extended as the study proceeds if needed based on emerging PK data. All participants will be contacted by telephone for an EoS visit/Day 16 (+/- 1 day) 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. Each participant will be given only the study drug preparation carrying his/her study number.
Intervention code [1] 329319 0
Treatment: Drugs
Comparator / control treatment
SION-719 suspension in equal parts Ora-Blend® flavoured suspending vehicle and Purified Water
Control group
Active

Outcomes
Primary outcome [1] 339157 0
To evaluate the effect of food on the PK profile of SION-719 in healthy participants
Timepoint [1] 339157 0
Plasma PK samples will be collected as follows:
Day 1 pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0 hours post-dose, Days 2 to 4 at 24, 36, 48, 60 and 72 hours, Day 5 pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0 hours post-dose, Days 6-8 at 24, 36, 48, 60 and 72 hours, Day 9 pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0 hours post-dose, and Days 10-12 at 24, 36, 48, 60, and 72 hours, and Early Termination (if applicable).
Secondary outcome [1] 438821 0
To assess the bioequivalence of SION-719 when administered as a solid oral formulation compared with suspension formulation in healthy participants
Timepoint [1] 438821 0
Plasma PK samples will be collected as follows:
Day 1 pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0 hours post-dose, Days 2 to 4 at 24, 36, 48, 60 and 72 hours, Day 5 pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0 hours post-dose, Days 6-8 at 24, 36, 48, 60 and 72 hours, Day 9 pre-dose and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0 hours post-dose, and Days 10-12 at 24, 36, 48, 60 and 72 hours, and Early Termination (if applicable).

Eligibility
Key inclusion criteria
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 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
1. Participant has clinically significant, in the opinion of the Investigator, 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 1 year.
3. Participant has clinically significant abnormalities in the opinion of the Investigator, on ECG, physical examination, or vital sign assessment at Screening or Day -1.
4. Participant has any single reading of QTcF greater than 470ms (females) or greater than 450ms (males) at Screening or Day -1.
5. Chronic or habitual alcohol (more than 10 standard drinks per week) or tobacco (more than 10 cigarettes per week) use or use of recreational drugs (greater than 1 use per month). The Investigator may exclude a participant with lower levels of alcohol, tobacco or recreational drug use based on discretion and the pattern or history of use.
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 prophylactic doses of vitamin/mineral supplements and occasional paracetamol or ibuprofen, which are allowed.
8. Participant has clinically significant abnormalities, in the opinion of the Investigator, at Screening or Day -1 on safety laboratory tests including serum chemistry, haematology, coagulation (coagulation done at screening only) tests, and urinalysis.
a. Participant must have an estimated glomerular filtration rate greater than 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 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. Healthy volunteers who have no evidence of cirrhosis and have completed a curative intent regimen for HCV, with a negative HCV polymerase chain reaction (PCR) test, will not be excluded.
10. Participant has a positive test for Coronavirus Disease 2019 (COVID-19) at 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 (with the exception of caffeine; see Inclusion Criterion 3), 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 CYP450 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 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 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, or any of the stated ingredients (including OraBlend® and hypromellose polymer).
17. Females who are breastfeeding or planning to breastfeed within 90 days of the EoS Visit.
18. Participant has an inability to follow a standardised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis
The food effect and bioequivalence cohort(s) will be evaluated by analysis of variance, with terms for sequence, period, and treatment as fixed effects and participant within sequence as a random effect for the SION-719 parameters Cmax and AUC8 (or AUCt if AUC8 cannot be calculated). The exposure measurements (AUC and Cmax) will be log-transformed prior to analysis. For the assessment of food effect, the 90% confidence interval (CI) for the ratio of population geometric means between tablet fed and tablet fasted will be provided for AUCt, AUC8 and Cmax. For the assessment of bioequivalence, the 90% CI for the ratio of population geometric means between test (tablet fasted) and reference conditions (suspension fasted) will be provided for AUCt, AUC8 and Cmax.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
18/12/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26967 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 43042 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 317225 0
Commercial sector/Industry
Name [1] 317225 0
Sionna Therapeutics, Inc
Country [1] 317225 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] 319503 0
Commercial sector/Industry
Name [1] 319503 0
Avance Clinical Pty Ltd
Address [1] 319503 0
Country [1] 319503 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315962 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315962 0
Ethics committee country [1] 315962 0
Australia
Date submitted for ethics approval [1] 315962 0
28/08/2024
Approval date [1] 315962 0
13/09/2024
Ethics approval number [1] 315962 0

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

Contacts
Principal investigator
Name 136358 0
Dr Gloria Wong
Address 136358 0
Nucleus Network Brisbane, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 136358 0
Australia
Phone 136358 0
+61737072720
Fax 136358 0
Email 136358 0
[email protected]
Contact person for public queries
Name 136359 0
Dr Gloria Wong
Address 136359 0
Nucleus Network Brisbane, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 136359 0
Australia
Phone 136359 0
+61 1800243733
Fax 136359 0
Email 136359 0
[email protected]
Contact person for scientific queries
Name 136360 0
Dr Gloria Wong
Address 136360 0
Nucleus Network Brisbane, Level 5, 300C Herston Road, Herston, Queensland, 4006
Country 136360 0
Australia
Phone 136360 0
+61 1800243733
Fax 136360 0
Email 136360 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.