Testing SION-451 combined with SION-2222 or SION-109 in healthy adults

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

This study tests whether combining the experimental drugs SION-451 with either SION-2222 or SION-109 is safe and how the body handles them in healthy adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 144 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Sionna Therapeutics Inc. (Industry-sponsored)
• Locations: 2 sites (Brisbane, Queensland and 1 other locations)
• Trial ID: NCT07035990 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, randomized, double-blind, placebo-controlled study focusing on Parts D and E, which will give multiple doses of SION-451 together with either SION-2222 (Part D) or SION-109 (Part E) to healthy adult participants. The main goals are to measure safety, tolerability, and pharmacokinetics of these combinations after repeated dosing. Parts A–C of the overall program have completed dosing, and these parts extend testing to combination regimens. Healthy volunteers will be closely monitored at clinical sites in Australia with standard safety labs, vital signs, and drug-level sampling.

Who should consider this trial

Good fit: Ideal candidates are healthy men or women aged 18–55 with BMI 18.0–32.0 kg/m2, weighing at least 45 kg, able to follow study restrictions (including temporary abstinence from alcohol, caffeine, smoking and certain foods), and willing to provide informed consent.

Not a fit: People with cystic fibrosis, those outside the 18–55 age range, or anyone with significant medical conditions are unlikely to receive direct benefit from participating in this healthy-volunteer study.

Why it matters

Potential benefit: If successful, this work could define safe dosing and drug behavior that help advance combination modulator therapies for people with cystic fibrosis.

How similar studies have performed: Other CF modulator combinations have produced major clinical benefits in patients, but these particular SION compounds are novel and the specific combination dosing is being tested for the first time in these parts.

Eligibility criteria

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.

Where this trial is running

Brisbane, Queensland and 1 other locations

• Nucleus Network — Brisbane, Queensland, Australia (Recruiting)
• Nucleus Network — Melbourne, Victoria, Australia (Recruiting)

Study contacts

• Principal investigator: Philip Ryan, MBBS, BMedSc, PhD, DPM, FFPM — Nucleus Network
• Study coordinator: Cecile LeCamus

Conditions Cystic Fibrosis