Safety, Tolerability, and Pharmacokinetics of Multiple Dose Combinations of SION-451 and Complementary Modulators SION-2222 and SION-109 in Healthy Participants.

NCT07035990 | Recruiting Phase 1

• 3 other identifiers: SION-451-101ACTRN12624000849895ACTRN12624000848505
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of Parts D and E of this Phase 1 study are to evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants.

Conditions

Cystic Fibrosis (CF)

Outcome Measures

Primary Outcomes (2)

• To evaluate the incidence of treatment emergent adverse events [Safety and Tolerability] of SION-451 and SION-109 when administered in combination to healthy participants

  Adverse reactions to the study drug combination SION-451 and SION-109 will be measured.

  From Day 1 through day 21

• To evaluate the incidence of treatment emergent adverse events [Safety and Tolerability] of SION-451 and SION-2222 when administered in combination to healthy participants

  Adverse events to the study drug combination SION-451 and SION-2222 will be measured

  From Day 1 through day 21

Secondary Outcomes (12)

• Cmax of SION-451 and SION-2222 in plasma when administered in combination to healthy participants

  From Day 1 through day 17

• Tmax of SION-451 and SION-2222 in plasma when administered in combination to healthy participants

  From Day 1 through day 17

• AUC of SION-451 and SION-2222 in plasma when administered in combination to healthy participants

  From Day 1 through day 17

• t1/2 of SION-451 and SION-2222 in plasma when administered in combination to healthy participants

  From Day 1 through day 17

• Volume of distribution of SION-451 and SION-2222 in plasma when administered in combination to healthy participants

  From Day 1 through day 17

Study Arms (4)

SION-451 + SION-2222

EXPERIMENTAL

All participants who receive SION-451 in combination with SION-2222

Drug: SION-451; Drug: SION-2222

Placebo matched to SION-451 and SION-2222

PLACEBO COMPARATOR

Drug: Placebo SION-451; Drug: Placebo SION-2222

SION 451 + SION 109

EXPERIMENTAL

All participants who receive SION-451 in combination with SION-109

Drug: SION-451; Drug: SION-109

Placebo matched to SION-451 and SION-109

PLACEBO COMPARATOR

Drug: Placebo SION-451; Drug: Placebo SION-109

Interventions

SION-451 DRUG

* Pharmaceutical form: tablet * Route of administration: oral

SION 451 + SION 109; SION-451 + SION-2222

SION-2222 DRUG

* Pharmaceutical form: capsule * Route of administration: oral

SION-451 + SION-2222

SION-109 DRUG

* Pharmaceutical form: tablet * Route of administration: oral

SION 451 + SION 109

Placebo SION-451 DRUG

Placebo matched to SION-451

Placebo matched to SION-451 and SION-109; Placebo matched to SION-451 and SION-2222

Placebo SION-2222 DRUG

Placebo matched to SION-2222

Placebo matched to SION-451 and SION-2222

Placebo SION-109 DRUG

Placebo matched to SION-109

Placebo matched to SION-451 and SION-109

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female adult participants aged 18 to 55 years, inclusive, at the time of consent.
• Weight of at least 45 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
• 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.
• Participant has read, understood, and voluntarily provided written informed consent
• Participant has an understanding, ability, and willingness to fully comply with study procedures and restrictions.

You may not qualify if:

• 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.
• 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.
• Participant has clinically significant abnormalities, in the opinion of the investigator, on ECG, physical examination, or vital sign assessment at Screening or Day -1.
• Participant has any single reading of QTcF \>470 ms (females) or \>450 ms (males) at Screening or Day -1.
• 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.

Sponsors & Collaborators

• Sionna Therapeutics Inc.: lead

Study Sites (2)

Nucleus Network

Brisbane, Queensland, 4006, Australia

RECRUITING

Nucleus Network

Melbourne, Victoria, 3004, Australia

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Philip Ryan, MBBS, BMedSc, PhD, DPM, FFPM

  Nucleus Network

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cecile LeCamus

CONTACT

617-819-1389; medinfo@sionnatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: June 25, 2025
• Study Start: July 23, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-08

Locations

AU (2)