Clinical trial NCT05795465: A Study of GEn-1124 in Subjects with Acute Respiratory Distress Syndrome (ARDS)
Official title: A Phase 2, Two-Part Study to Evaluate the Safety and Tolerability of GEn-1124 in Subjects with Acute Respiratory Distress Syndrome (ARDS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Respiratory Distress Syndrome, Acute
Lead sponsor: GEn1E Lifesciences
Sponsor class: INDUSTRY
First posted: 2023-04-03
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 - Randomized, double-blind, dose escalation. Part 2 - Randomized, double-blind, placebo controlled, parallel group.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female subject between the ages of 18 and 80 years old, inclusive.
2. Written informed consent .
3. Dosing as early as possible after first meeting ARDS 2023 Global definition.
4. Acceptable method of birth control.

Exclusion Criteria:

1. Subject, surrogate, or physician not committed, or eligible, to receive full supportive care measures.
2. Pregnant or breastfeeding
3. Currently incarcerated in a correctional institution or involuntarily committed to an inpatient mental health facility.
4. Active malignancy (other than non-melanoma skin cancer) requiring treatment within the last 3 months or within the last 6 months if an anti-B cell antibody was received.
5. Any other irreversible disease or condition for which 6-month mortality is estimated to be \>50%.
6. Moderate to severe liver failure.
7. Estimated glomerular filtration rate (eGFR) \<10 mL/min/1.73 m2 or requiring dialysis at screening.
8. Acute Left ventricular failure or congestive heart failure, defined as New York Heart Association Class IV.
9. Severe chronic respiratory disease with continuous home oxygen \>2 liters per minute (LPM) or \>28% (adjusted for altitude); and/or home noninvasive ventilation (except for the treatment of obstructive sleep apnea).
10. 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.
11. History of any type of solid organ or cellular transplant.
12. Receiving immunosuppressive therapy for solid organ or hematopoietic cancer, transplant anti-rejection medication, and/or other chronic conditions.
13. Moribund subject not expected to survive 24 hours.
14. Do not resuscitate (DNR) status.
15. World Health Organization (WHO) functional class III or IV pulmonary hypertension.
16. Burn victims currently undergoing treatment for \>20% total body surface area (TBSA) involvement or for known airway inhalation injury.
17. Neuromuscular disease that could impact ability to wean from mechanical ventilation.
18. 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).
19. Active Hepatitis B, positive Hepatitis C (and has not completed antiviral treatment), or positive human immunodeficiency (HIV) screen.
20. Use of any investigational drug or device within last 30 days of dosing or 5 half-lives, whichever is longer.
21. 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.

Primary outcomes:
measure: To assess the safety and tolerability (SAEs and TEAEs) of GEn-1124
timeFrame: Through study completion, Day 60
Secondary outcomes:
Other outcomes:
measure: Change in oxygenation index (OI).
timeFrame: Through study completion, Day 60
measure: Change in ratio of arterial oxygen partial pressure to fractional inspired oxygen.
timeFrame: Through study completion, Day 60
measure: Change in static compliance.
timeFrame: Through study completion, Day 60
measure: Change in dynamic compliance.
timeFrame: Through study completion, Day 60
measure: Change in the Radiographic Assessment of Lung Edema (RALE) score
timeFrame: Through study completion, Day 60
measure: Duration on invasive mechanical ventilation.
timeFrame: Through study completion, Day 60
measure: Duration of any ventilatory support.
timeFrame: Through study completion, Day 60
measure: Number of Ventilator Free Days (VFDs)
timeFrame: Up to Day 28
measure: Intubation (in subjects not previously intubated)
timeFrame: Through study completion, Day 60
measure: Reintubation (after extubation) (if applicable).
timeFrame: Through study completion, Day 60
measure: Change in Sequential Organ Failure Assessment (SOFA) score.
timeFrame: Through study completion, Day 60
measure: Incidence of hospital mortality.
timeFrame: Up to Day 28
measure: Incidence of all-cause mortality.
timeFrame: Up to Day 28
measure: Duration in ICU.
timeFrame: Through study completion, Day 60
measure: Duration in hospital.
timeFrame: Through study completion, Day 60
measure: Proportion of subjects alive and free of respiratory failure or extracorporeal membrane oxygenation (ECMO)).
timeFrame: Through study completion, Day 60
measure: Hierarchical Alive and Ventilator Free (AVF) score.
timeFrame: Through study completion, Day 60
measure: Time to recover gas exchange
timeFrame: Up to Day 28
measure: Change in Short Form 36 Health Survey Questionnaire (SF-36).
timeFrame: Days 9 through 60
measure: Change in Euro Quality of Life Health Survey (EQ-5D-5L).
timeFrame: Days 9 through 60
measure: Peak plasma concentration (Cmax) for GEn-1124 and its metabolites.
timeFrame: Days 1 through 6
measure: Terminal elimination rate constant (Kel) and half-life (T1/2) in plasma for GEn-1124 and its metabolites.
timeFrame: Days 1 through 6
measure: Area under the plasma concentration versus time curve (AUC) for GEn-1124 and its metabolites.
timeFrame: Days 1 through 6
measure: Plasma volume of distribution (Vss) for GEn-1124 and its metabolites.
timeFrame: Days 1 through 6
measure: Plasma Clearance (CL) for GEn-1124 and its metabolites.
timeFrame: Days 1 through 6
measure: Plasma concentration at steady state (Css) for GEn-1124 and its metabolites.
timeFrame: Days 1 through 6
measure: Measure protein biomarkers in whole blood.
timeFrame: Days 1 through 6
measure: Measure protein biomarkers in bronchoalveolar lavage (BAL) fluid.
timeFrame: Days 1 through 6
measure: Measure protein biomarkers in tracheal aspirate (TA).
timeFrame: Days 1 through 6
Locations:
city: Washington, D.C.
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ocean Springs
country: United States
facility: Ocean Springs Hospital
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
Study officials:
affiliation: GEn1E Lifesciences
name: Ritu Lal, PhD, MS
role: STUDY_DIRECTOR
References: