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

Phase 1

Not yet recruiting

• Conditions: Cystic Fibrosis (CF)
• Interventions: Drug: Placebo SION-451; Drug: SION-451; Drug: SION-2222; Drug: Placebo SION-2222; Drug: SION-109; Drug: Placebo SION-109

• Registration Number: NCT07035990
• Lead Sponsor: Sionna Therapeutics Inc.

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.

Detailed Description

This is a Phase 1 randomized, double-blind, placebo-controlled study. Parts D and E will evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants. Parts A, B, and C of this study have completed dosing.

Part D will involve multiple dosing of SION-451 and SION-2222 in combination. Part E will involve multiple dosing of SION-451 and SION-109 in combination.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-16
• Last Update Submitted: 2025-06-16
• Study First Posted: 2025-06-25
• Last Update Posted: 2025-06-25
• Study Start: 2025-07-01
• Primary Completion: 2026-06
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 144

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.

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 >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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo matched to SION-451 and SION-2222	Placebo SION-451	-
SION-451 + SION-2222	SION-451	All participants who receive SION-451 in combination with SION-2222
SION-451 + SION-2222	SION-2222	All participants who receive SION-451 in combination with SION-2222
Placebo matched to SION-451 and SION-2222	Placebo SION-2222	-
SION 451 + SION 109	SION-451	All participants who receive SION-451 in combination with SION-109
SION 451 + SION 109	SION-109	All participants who receive SION-451 in combination with SION-109
Placebo matched to SION-451 and SION-109	Placebo SION-451	-
Placebo matched to SION-451 and SION-109	Placebo SION-109	-

Primary Outcome Measures

Name	Time	Method
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	From Day 1 through day 21	Adverse reactions to the study drug combination SION-451 and SION-109 will be measured.
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	From Day 1 through day 21	Adverse events to the study drug combination SION-451 and SION-2222 will be measured

Secondary Outcome Measures

Name	Time	Method
Apparent total clearance of SION-451 and SION-109 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
Apparent total clearance of SION-451 and SION-2222 in plasma when administered in combination to healthy participants	From Day 1 through day 17
Cmax of SION-451 and SION-109 in plasma when administered in combination to healthy participants	From Day 1 through day 17
Tmax of SION-451 and SION-109 in plasma when administered in combination to healthy participants	From Day 1 through day 17
AUC of SION-451 and SION-109 in plasma when administered in combination to healthy participants	From Day 1 through day 17
t1/2 of SION-451 and SION-109 in plasma when administered in combination to healthy participants	From Day 1 through day 17
Volume of distribution of SION-451 and SION-109 in plasma when administered in combination to healthy participants	From Day 1 through day 17
Cmax of SION-451 and SION-2222 in plasma when administered in combination to healthy participants	From Day 1 through day 17

Trial Locations

Locations (1)

Nucleus Network; 🇦🇺 Melbourne, Victoria, Australia