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Trial registered on ANZCTR


Registration number
ACTRN12624000848505
Ethics application status
Approved
Date submitted
1/07/2024
Date registered
9/07/2024
Date last updated
9/07/2024
Date data sharing statement initially provided
9/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public 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-451 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-451 in healthy participants - Part C
Secondary ID [1] 312431 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 334247 0
Condition category
Condition code
Human Genetics and Inherited Disorders 330912 330912 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, randomised, open label study designed to evaluate the effect of food on the pharmacokinetics (PK) of SION-451, and the bioequivalence of a solid oral formulation compared to an oral suspension.

This study will include a Screening Period, a Treatment Period, and an End of Study (EoS) visit. 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 CRU on Day -1. On the following morning (Day 1), each participant will be randomised to 1 of 3 open-label SION-451 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-451 in Period 1, dose to be determined (TBD); a dose not exceeding 750mg will be selected at or below a dose that has been safe and well tolerated in the prior single ascending dose (SAD) study. Following a washout period of at least 72 hours (actual duration will be determined prior to the start of this study, participants will receive the second dose of SION-451 in Period 2 of the sequence (Day 5). Following a washout period of at least 72 hours (actual duration will be determined prior to the start of this study), participants will receive the third dose of SION 451 in Period 3 of the sequence (Day 9). The day of dosing in Periods 2 and 3 will be adjusted if needed, to enable the washout period. 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 1 a single oral dose of SION-451 given as a tablet under fasted conditions. Treatment II a single oral dose of SION-451 given as a suspension under fasted conditions (as above) and Treatment III, a single oral dose 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 will be extended as the study proceeds if needed based on emerging PK data. 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 the 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 electronic case report form (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] 328937 0
Treatment: Drugs
Comparator / control treatment
Placebo: SION-451 oral suspension in Ora Blend and purified water
Control group
Active

Outcomes
Primary outcome [1] 338677 0
To evaluate the effect of food on the PK profile of SION-451 in healthy participants
Timepoint [1] 338677 0
Plasma samples for food effect on PK will be collected as follows:
Day 1 pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12 and 16 hours post-dose, Days 2 through 4 at 24, 36 48, 60 and 72 hours, Days 6 through 8 at 24, 36 48, 60 and 72 hours, Days 10 through 12 at 24, 36 48, 60 and 72 hours and Early Termination (if applicable)
Secondary outcome [1] 436993 0
To assess the bioequivalence of SION-451 when administered as a tablet formulation compared with suspension formulation in healthy participants
Timepoint [1] 436993 0
Plasma samples for PK will be collected as follows:
Day 1 pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12 and 16 hours post-dose, Days 2 through 4 at 24, 36 48, 60 and 72 hours, Days 6 through 8 at 24, 36 48, 60 and 72 hours, Days 10 through 12 at 24, 36 48, 60 and 72 hours and Early Termination (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 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. 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 >470 ms (females) or >450 ms (males) at Screening or Day -1.
5. Chronic or habitual alcohol (>10 standard drinks per week) or tobacco (>10 cigarettes per week) use or use of recreational drugs (>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 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. 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. Please refer to private notes for additional exclusion criteria.
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), 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 End of Study 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 End of Study Telephone Contact visit.
15. Participant has donated or lost greater than 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 go days of the End of Study 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
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-451 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 test (fed) and reference conditions (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 (fasted tablet) and reference conditions (fasted suspension) will be provided for AUCt, AUC8 and Cmax.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
9/07/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26746 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 42793 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 316848 0
Commercial sector/Industry
Name [1] 316848 0
Sionna Therapeutics, Inc
Country [1] 316848 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] 319080 0
Commercial sector/Industry
Name [1] 319080 0
Avance Clinical Pty Ltd
Address [1] 319080 0
Country [1] 319080 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315611 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315611 0
Ethics committee country [1] 315611 0
Australia
Date submitted for ethics approval [1] 315611 0
05/06/2024
Approval date [1] 315611 0
01/07/2024
Ethics approval number [1] 315611 0

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

Contacts
Principal investigator
Name 135246 0
Dr Philip Ryan
Address 135246 0
Nucleus Network Melbourne, 235 Ryrie Street, Geelong, 3220, Victoria
Country 135246 0
Australia
Phone 135246 0
+61 3 85939801
Fax 135246 0
Email 135246 0
p.ryan@nucleusnetwork.com.au
Contact person for public queries
Name 135247 0
Nucleus Network Melbourne
Address 135247 0
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 135247 0
Australia
Phone 135247 0
+61 1800 243 733
Fax 135247 0
Email 135247 0
melbourne@nucleusnetwork.com
Contact person for scientific queries
Name 135248 0
Nucleus Network Melbourne
Address 135248 0
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne, Victoria, 3004
Country 135248 0
Australia
Phone 135248 0
+61 1800 243 733
Fax 135248 0
Email 135248 0
melbourne@nucleusnetwork.com

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.