A Study of GEn-1124 in Subjects With Acute Respiratory Distress Syndrome (ARDS)

Study Overview
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Brief Summary
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GEn1E-1124-002 is a two-part Phase 2 study to evaluate the safety and tolerability of GEn-1124 in subjects with ARDS. Treatment with IV infusion dosing as early as possible after ARDS diagnosis. Subjects will be given a second dose approximately 8 hours after the first dose and will continue with twice daily dosing (BID regimen) for 5 days.

Detailed Description
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Randomized , double-blind, placebo controlled, dose escalation study to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of GEn1124. GEn-1124 or placebo will be administered as a 2-hour IV infusion as early as possible after ARDS diagnosis. Participants will receive a second dose approximately 8 hours after the first and will continue BID for the remaining schedule (Days 2-5). Follow-up will be for a total of 60 days after the first dose or death (whichever comes first). An independent Safety Review Committee (SRC) will be responsible for reviewing data throughout the study.

Official Title
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A Phase 2, Two-Part Study to Evaluate the Safety and Tolerability of GEn-1124 in Subjects With Acute Respiratory Distress Syndrome (ARDS)

Conditions
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Respiratory Distress Syndrome, Acute

Intervention / Treatment
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* Drug: GEn-1124
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject between the ages of 18 and 80 years old, inclusive. Written informed consent . Hospital admission. Dosing as early as possible after first meeting ARDS 2023 Global definition. Acceptable method of birth control. Exclusion Criteria: Subject, surrogate, or physician not committed, or eligible, to receive full supportive care measures. Pregnant or breastfeeding Currently incarcerated in a correctional institution or involuntarily committed to an inpatient mental health facility. Active malignancy (other than non-melanoma skin cancer) requiring treatment within the last 6 months. Any other irreversible disease or condition for which 6-month mortality is estimated to be >50%. Moderate to severe liver failure. Acute or chronic kidney disease. Unstable cardiac disease. Severe chronic respiratory disease with a partial pressure of carbon dioxide (PaCO2) >50 mmHg or the use of home oxygen. Poly-traumatic injury resulting in significant blood loss and/or likely to require major surgery within the study period, or subject condition that would interfere with study procedures. History of any type of solid organ or cellular transplant. Chronic use of immunosuppressants, including corticosteroids. Moribund subject not expected to survive 24 hours. Do not resuscitate (DNR) status. World Health Organization (WHO) functional class III or IV pulmonary hypertension. Burn victims currently undergoing treatment for >20% total body surface area (TBSA) involvement or for known airway inhalation injury. Neuromuscular disease that could impact ability to wean from mechanical ventilation. History of tuberculosis (TB); undergoing treatment for latent TB infection (LTBI); untreated LTBI (as determined by documented results within 3 months of Screening of a positive TB test). Active Hepatitis B, positive Hepatitis C (and has not completed antiviral treatment), or positive human immunodeficiency (HIV) screen. Use of any investigational drug or device within last 30 days of dosing or 5 half-lives, whichever is longer. Any other medical, psychiatric, or social condition that, in the opinion of the investigator, is likely to unfavorably alter the risk-benefit of subject participation, to interfere with protocol compliance, or to confound safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 - Randomized, double-blind, dose escalation. Part 2 - Randomized, double-blind, placebo controlled, parallel group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Cohort 1: GEn-1124<br>Subjects in cohort 1 will receive low dose GEn-1124 BID intravenous 5 days. | Drug: GEn-1124<br>* Intravenous infusion<br>|
| Experimental: Part 1 Cohort 2: GEn-1124<br>Subjects in cohort 2 will receive high dose GEn-1124 BID intravenous for 5 days. | Drug: GEn-1124<br>* Intravenous infusion<br>|
| Placebo Comparator: Placebo<br>Subjects randomized to placebo will receive a placebo in a matching dosing regimen (Placebo BID intravenous for 5 days). | Drug: Placebo<br>* Intravenous infusion<br>|
| Experimental: Part 2: GEn-1124<br>Depending on the analysis of part 1, subjects in part 2 will receive GEn-1124 BID intravenous for 5 days. | Drug: GEn-1124<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability (SAEs and TEAEs) of GEn-1124 | Incidence (frequency over time) of serious adverse events (SAEs) unexpected in ARDS patients. Incidence (frequency over time) of treatment-emergent adverse events (TEAE). | Through study completion, Day 60 |