Inhaled RB042 in Healthy Adult Volunteers and Healthy Adult Smokers

RAGE Bio

Status and phase: Enrolling; Phase 1

Conditions: Healthy Smoker; Healthy

Treatments: Drug: RB042; Drug: Placebo inhalation solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT07285122

RB042_1001

Details and patient eligibility

About

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

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 8 patient groups

Cohort A1

Experimental group

Description:

Participants will receive RB042 (Dose Level A1) or matching placebo on Day 1.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort A2

Experimental group

Description:

Participants will receive RB042 (Dose Level A2) or matching placebo on Day 1.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort A3

Experimental group

Description:

Participants will receive RB042 (Dose Level A3) or matching placebo on Day 1.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort A4

Experimental group

Description:

Participants will receive RB042 (Dose Level A4) or matching placebo on Day 1.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort B1

Experimental group

Description:

Participants will receive RB042 (Dose Level B1) or matching placebo on Days 1, 8, 15, and 22.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort B2

Experimental group

Description:

Participants will receive RB042 (Dose Level B2) or matching placebo on Days 1, 8, 15, and 22.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort B3

Experimental group

Description:

Participants will receive RB042 (Dose Level B3) or matching placebo on Days 1, 8, 15, and 22.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042

Cohort C1

Experimental group

Description:

Participants will receive RB042 (Dose Level C1) or matching placebo on Days 1, 8, 15, and 22.

Treatment:

Drug: Placebo inhalation solution

Drug: RB042