Inhaled RB042 in healthy adults and adult smokers

A Phase I, Randomised, Double Blind, Placebo-controlled, Dose-escalating Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of RB042 Administered Via Inhalation to Healthy Adult Volunteers and Healthy Adult Smokers

This trial will try an inhaled medicine called RB042 to see if it is safe and how the body handles it in healthy adults and current adult smokers.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: RAGE Bio (Industry-sponsored)
• Locations: 1 site (Nedlands, Western Australia)
• Trial ID: NCT07285122 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, randomized, double-blind, placebo-controlled, three-part Phase 1 trial of inhaled RB042 focused on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Part A administers a single dose to healthy volunteers, while Parts B and C give multiple doses to healthy volunteers and to healthy adult smokers, respectively. Participants will attend multiple site visits and include inpatient stays (4 days in Part A; up to 17 days plus a short rehospitalization in Parts B and C) with follow-up over several months. Primary endpoints are safety and tolerability, with PK/PD sampling to characterize systemic and pulmonary exposure.

Who should consider this trial

Good fit: Healthy adults (and a separate group of current adult smokers with ≥10 pack-years) with normal lung function (FEV1 ≥80% predicted and FEV1/FVC ≥0.7), BMI 18.0–32.0 kg/m2, not pregnant or lactating, and willing to use effective contraception are the intended participants.

Not a fit: People with significant medical conditions, abnormal lung function, recent or chronic respiratory disease, pregnant or breastfeeding individuals, or those otherwise excluded by the protocol are unlikely to benefit from participating.

Why it matters

Potential benefit: If RB042 is safe and shows predictable lung exposure, it could enable development of a new inhaled therapy approach for respiratory conditions in the future.

How similar studies have performed: This is the first-in-human trial of RB042 specifically, although randomized, placebo-controlled inhaled PK/PD Phase 1 trials are a standard and established step in respiratory drug development.

Eligibility criteria

Inclusion Criteria:

* Participants must be overtly healthy as determined by medical evaluation
* Part C only: have a ≥10 pack years smoking history, have smoked tobacco products (cigarettes, cigars, or equivalent) regularly for the past 12 months, and currently smoke daily.
* Have forced expiratory volume (FEV1) ≥80% predicted and FEV1 to FVC ratio (FEV1/FVC) ≥0.7 at Screening and on Day -1
* Body weight at least 50 kg and have a body mass index (BMI) within the range 18.0 and 32.0 kg/m2 (inclusive)
* Women of childbearing potential (WOCBP) must have a negative pregnancy test and must not be lactating.
* Participants must agree to use an approved method(s) of highly effective contraception as defined in the protocol.

Exclusion Criteria:

* Clinically significant history or presence of gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, neurologic, hematologic, metabolic, autoimmune, or oncologic disorders that may affect safety or study outcomes.
* Chronic or active respiratory disease (e.g., asthma, COPD) or history of angioedema within 3 years.
* Active or chronic liver disease, or abnormal liver function tests (ALT, AST, or bilirubin outside reference range, except Gilbert's syndrome).
* QTcF \>450 msec (males) or \>470 msec (females).
* Renal impairment (creatinine clearance \<90 mL/min) or thrombocytopenia (\<150 × 10⁹/L).
* Positive test for hepatitis B surface or core antigen, hepatitis C (unless HCV-RNA negative), or HIV.
* Active respiratory infection within 5 days before study start.
* Recent or concurrent use of medications, herbal supplements, vaccines, or blood products that could interfere with study safety or interpretation.
* Participation in another investigational study within 30 days, or blood donation \>400 mL within 30 days.
* Parts A and B only: Regular smoking (≥1 day per week) within 6 months prior to dosing, or a positive urine cotinine test at screening or Day -1.
* Excessive alcohol consumption (\>21 drinks/week for males or \>14 for females).
* History of severe drug reaction or anaphylaxis.
* Contraindication to, or unwillingness to undergo, bronchoscopy.
* Any psychiatric or medical condition that, in the investigator's opinion, could compromise safety or compliance.

Where this trial is running

Nedlands, Western Australia

• Linear Clinical Research — Nedlands, Western Australia, Australia (Recruiting)

Study contacts

• Study coordinator: Chief Medical Officer

Conditions Healthy; Healthy Smoker