Inhaled RB042 in Healthy Adult Volunteers and Healthy 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 is a 3-part, randomised, double-blind, placebo-controlled, first in human study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of inhaled RB042.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Healthy Smoker
• Intervention / Treatment: Drug: RB042; Drug: Placebo inhalation solution

Detailed Description

The purpose of this study is to measure the safety, tolerability, PK, and PD of inhaled RB042 compared with inhaled placebo in healthy adult volunteers and healthy adult smokers.

Study details include:

• Overall study duration of up to 14 months.
• Participants in Part A (healthy adult volunteers) will be required to visit the study site for assessments on 11 occasions, including a 4-day in-house stay, over 4 months.
• Participants in Parts B (healthy adult volunteers) and C (healthy adult smokers) will be required to visit the study site for assessments on 13 occasions, including a 17-day (Day -1 to 16) and 3-day (Day 21 to 24) in-house stay, over 5 months.
• Participants will be administered a single dose (Part A) or multiple doses (Parts B and C) of study intervention.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chief Medical Officer; Phone Number: 1800312514; Email: clinicaltrialdisclosure@ragebio.com

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1; Participants will receive RB042 (Dose Level A1) or matching placebo on Day 1.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort A2; Participants will receive RB042 (Dose Level A2) or matching placebo on Day 1.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort A3; Participants will receive RB042 (Dose Level A3) or matching placebo on Day 1.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort A4; Participants will receive RB042 (Dose Level A4) or matching placebo on Day 1.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort B1; Participants will receive RB042 (Dose Level B1) or matching placebo on Days 1, 8, 15, and 22.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort B2; Participants will receive RB042 (Dose Level B2) or matching placebo on Days 1, 8, 15, and 22.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort B3; Participants will receive RB042 (Dose Level B3) or matching placebo on Days 1, 8, 15, and 22.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.
Experimental: Cohort C1; Participants will receive RB042 (Dose Level C1) or matching placebo on Days 1, 8, 15, and 22.	Drug: RB042; A single or multiple doses of RB042 will be administered via a nebuliser.; Drug: Placebo inhalation solution; A single or multiple doses of placebo will be administered via a nebuliser.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and frequency of treatment-emergent adverse events (TEAEs)	To assess the safety and tolerability of single and multiple doses of RB042 when administered via a nebuliser to healthy adult volunteers and healthy adult smokers	From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax)	To characterize the Cmax of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers	From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B)
Time to maximum concentration (Tmax)	To characterize the Tmax of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers	From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B)
Terminal elimination half-life (t½)	To characterize the t½ of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers	From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B)
Area under the concentration-time curve (AUC)	To characterize the AUC of RB042 following single and multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers	From Day 1 until the end of the study (Day 85 for Part A; Day 106 for Parts A and B)
Trough concentration	To characterize the AUC of RB042 following multiple doses of RB042 administered via a nebuliser to healthy adult volunteers and healthy adult smokers	On Days 7, 14, and 21

Collaborators and Investigators

• Sponsor: RAGE Bio

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: December 3, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: RB042_1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No