A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GNS-3545 in Healthy Participants

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose, Multiple Ascending Dose, and Food-effect Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GNS-3545 in Healthy Adult Subjects

This is a randomized, double-blind, placebo-controlled Phase 1 study of SAD (Part 1) and MAD (Part 2) of orally administered GNS-3545 in healthy adult subjects. The food effect will be assessed in one cohort in Part 1.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: GNS-3545; Drug: GNS-3545 Placebo

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: GNS-3545 Study Team; Phone Number: 617-494-1460; Email: GNS_Clinical@genosco.com

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Pharmaron CPC, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy, adult, male or female (of non-childbearing potential only), 18-55 years of age
• Male subjects must follow protocol specified contraception guidance
• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing
• BMI ≥ 18.0 and ≤ 32.0 kg/m2 at the screening visit and body weight of ≥ 50 kg
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, or vital signs, as deemed by the PI or designee
• No ECG findings of clinical significance as judged by the PI or qualified designee
• Understands the study procedures in the ICF and be willing and able to comply with the protocol

Exclusion Criteria:

• Is mentally or legally incapacitated or has significant emotional problems
• History or presence of clinically significant medical or psychiatric conditions
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study
• Surgical procedure or Administration of a live vaccination within 30 days prior to the first dose of the study drug
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing
• History or presence of hepatic impairment
• History or presence of significant cardiovascular conditions or risk factors
• Subjects with a higher risk of adverse events in the setting of blood pressure decreases
• History or presence of hypersensitivity to compounds related to the study drug excipients
• Allergy to non-latex band aids, adhesive dressing, or medical tape
• Female subjects of childbearing potential or Female subject with a positive pregnancy test or who is lactating
• Positive urine drug or serum alcohol results
• Positive results at the screening visit for HIV, HBsAg, or HCV, or a clinically significant history of infection within 3 months prior to screening
• Inability or unwillingness to avoid use of medications, supplements, or substances that may affect CYP enzymes, drug transporters, blood pressure, or QT/QTc interval within the specified washout periods prior to dosing
• Has been on a diet incompatible with the on-study diet, or unable to swallow multiple tablets by mouth
• Has donated or lost more than 500 mL of blood within 56 days prior to the first dosing, or Plasma donation within 7 days prior to the first dosing
• Subjects with dietary restrictions that would prevent subjects from consuming a high-fat/high-calorie meal
• Participation in another clinical study within 30 days or 5 half-lives of the product prior to the first dosing
• Any reason determined by the PI or designee, in their opinion, that would prevent the subject's participation in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GNS-3545; Part 1 (SAD): Six participants will be randomized to receive a single dose of GNS-3545 at the assigned dose level, while two participants will receive matching placebo. Part 2 (MAD): Six participants will be randomized to receive multiple doses of GNS-3545 at the assigned dose level once daily for 14 consecutive days, while two participants will receive matching placebo.	Drug: GNS-3545; GNS-3545 will be administered as oral tablets at assigned dose levels to six of the eight participants within each cohort in Part 1 (SAD) and Part 2 (MAD). In Part 1, participants will receive a single dose on one occasion (Day 1). In Part 2, participants will receive daily dosing for 14 consecutive days.
Placebo Comparator: GNS-3545 Placebo; Part 1 (SAD): Six participants will be randomized to receive a single dose of GNS-3545 at the assigned dose level, while two participants will receive matching placebo. Part 2 (MAD): Six participants will be randomized to receive multiple doses of GNS-3545 at the assigned dose level once daily for 14 consecutive days, while two participants will receive matching placebo.	Drug: GNS-3545 Placebo; The placebo will be administered as oral tablets identical in appearance to the GNS-3545 tablets to two of the eight participants within each cohort in Part 1 (SAD) and Part 2 (MAD). In Part 1, participants will receive a single placebo dose on one occasion (Day 1). In Part 2, participants will receive once-daily placebo doses for 14 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Emergent Adverse Events (TEAEs)	Number and severity of treatment-emergent adverse events (TEAEs) following single and multiple doses of GNS-3545 and placebo	Collection of TEAEs occurs from the point of first dose administration (Day 1 in each part) through to study completion (up to 8 days from the first dosing for Part 1 & up to 8 days from the last dosing for Part 2).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the time-concentration curve (AUC) from zero (pre-dose) to 24 hours (h) post-dose sample [0-24 h])	Pharmacokinetic profile of GNS-3545 and its active metabolite in plasma	Up to 4 days from the last dosing for Part 1 (SAD), Up to 4 days from the last dosing for Food Effect Cohort (Part 1), Up to 17 days from the last dosing for Part 2 (MAD)
Area under the time-concentration curve (AUC) from zero (pre-dose) to the time of the last measurable concentration (t) [0-t])	Pharmacokinetic profile of GNS-3545 and its active metabolite in plasma	Up to 4 days from the last dosing for Part 1 (SAD), Up to 4 days from the last dosing for Food Effect Cohort (Part 1), Up to 17 days from the last dosing for Part 2 (MAD)
Maximum observed concentration (Cmax) after a single dose and at steady state (Cmax,ss)	Pharmacokinetic profile of GNS-3545 and its active metabolite in plasma	Cmax for up to 4 days from the last dosing for Part 1 (SAD), Cmax for up to 4 days from the last dosing for Food Effect Cohort (Part 1), Cmax & Cmax,ss up to 17 days from the last dosing for Part 2 (MAD)
Time to reach maximum observed concentration (Tmax) after a single dose and at steady state (Tmax,ss)	Pharmacokinetic profile of GNS-3545 and its active metabolite in plasma	Tmax up to 4 days from the last dosing for Part 1 (SAD), Tmax for up to 4 days from the last dosing for Food Effect Cohort (Part 1), Tmax & Tmax,ss up to 17 days from the last dosing for Part 2 (MAD)
Cumulative amount excreted in urine over the collection interval (CumAe) after a single dose and at steady state (CumAe,ss)	Pharmacokinetic profile of GNS-3545 and its active metabolite in urine	CumAe for up to 4 days from the last dosing for Part 1 (SAD), CumAe,ss up to 17 days from the last dosing for Part 2 (MAD)
Lag time before the first measurable concentration (Tlag)	Pharmacokinetic profile of GNS-3545 and its active metabolite in plasma	Up to 4 days from the last dosing for Food Effect Cohort Only (Part 1)

Collaborators and Investigators

• Sponsor: Genosco Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2025
• Primary Completion (Estimated): June 12, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: October 28, 2025
• First Submitted That Met QC Criteria: November 4, 2025
• First Posted (Estimated): November 6, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 23, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: GNS-3545-P101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this stage, it is not planned that any IPD information will be shared.

Drug and device information, study documents

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