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

Respiratory Distress Syndrome, Acute Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05795465
• Other study ID #: GEn-1124-002
• Status: Recruiting
• Phase: Phase 2
• Start date: April 4, 2023
• Est. completion date: July 2024

Study information

• Verified date: April 2024
• Source: GEn1E Lifesciences
• Contact: Ritu Lal, PhD, MS
• Phone: 650-485-3279
• Email: clinical[@]gen1elifesci.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: July 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Male or female subject between the ages of 18 and 80 years old, inclusive.

2. Written informed consent .

3. Hospital admission.

4. Dosing as early as possible after first meeting ARDS 2023 Global definition.

5. 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) <30 mL/min/1.73 m2 or requiring dialysis prior to hospitalization.

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Acute
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• GEn-1124
Intravenous infusion
• Placebo
Intravenous infusion

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	The Mount Sinai Hospital	New York	New York
United States	Ocean Springs Hospital	Ocean Springs	Mississippi
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
GEn1E Lifesciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in oxygenation index (OI).	Oxygenation Index is calculated as PAW × FiO2 × 100 / SpO2 where PAW is product of mean airway pressure (PAW), FiO2 is fraction of inspired oxygen, and SpO2 is pulse oxygen saturation (as long as the lowest SpO2 measurement for the day was < 97%).	Through study completion, Day 60
Other	Change in ratio of arterial oxygen partial pressure to fractional inspired oxygen.	Ratio of arterial oxygen partial pressure to fractional inspired oxygen is calculated as PaO2 / FiO2 where PaO2 indicates arterial oxygen partial pressure and FiO2 indicates fraction of inspired oxygen. All values are derived from ventilator parameters and arterial blood gas.	Through study completion, Day 60
Other	Change in static compliance.	Static compliance is calculated as the tidal volume divided by the difference between airway plateau pressure and end-expiratory pressure (Pplat - PEEP) where Plat is airway plateau pressure and PEEP is positive end-expiratory pressure. All values are derived from ventilator parameters.	Through study completion, Day 60
Other	Change in dynamic compliance.	Dynamic compliance is calculated as the tidal volume divided by the difference between peak inspiratory pressure and end-expiratory pressure (PIP - PEEP) where Plat is airway plateau pressure and PEEP is positive end-expiratory pressure. All values are derived from ventilator parameters.	Through study completion, Day 60
Other	Change in the Radiographic Assessment of Lung Edema (RALE) score	To calculate RALE, each radiographic quadrant is scored for extent of consolidation (0-4) and density of opacification (1-3). The product of the consolidation and density scores for each of the four quadrants is summed (minimum score=0, maximum score=48; higher scores mean worse outcome).	Through study completion, Day 60
Other	Duration on invasive mechanical ventilation.	Duration of invasive mechanical ventilation is defined as the number of hours that the subject receives invasive mechanical ventilation for at least 1 hour duration.	Through study completion, Day 60
Other	Duration of any ventilatory support.	Duration of ventilatory support is defined as the number of hours that the subject receives any ventilation support for at least 1 hour duration.	Through study completion, Day 60
Other	Number of Ventilator Free Days (VFDs)	VFDs to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least 48 hours after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a subject was receiving assisted breathing at day 27 or dies prior to day 28, VFDs will be zero. Subjects transferred to another hospital or other health care facility will be followed to day 28 to assess this endpoint.	Up to Day 28
Other	Intubation (in subjects not previously intubated)	Intubation is defined as the need for initial intubation in subjects who are not intubated at baseline.	Through study completion, Day 60
Other	Reintubation (after extubation) (if applicable).	Reintubation is defined as the need for reintubation after initial successful extubation for 48 hours.	Through study completion, Day 60
Other	Change in Sequential Organ Failure Assessment (SOFA) score.	The SOFA score is used for prediction of mortality in ICU patients. Initial and highest scores of more than 11 or mean scores of more than 5 corresponded to mortality of more than 80%.	Through study completion, Day 60
Other	Incidence of hospital mortality.	Hospital mortality is defined as mortality that occurred during hospitalization up to Day 28, defined as 672 hours from the time of randomization. All subjects will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28."	Up to Day 28
Other	Incidence of all-cause mortality.	All-cause mortality is defined that occurred for any cause up to Day 28, defined as 672 hours from the time of randomization. All subjects will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28."	Up to Day 28
Other	Duration in ICU.	Length of ICU stay is defined as the number of hours in the ICU for at least 1 hour duration.	Through study completion, Day 60
Other	Duration in hospital.	Length of hospital stay will be defined as the number of hours hospitalized for at least 1 hour duration.	Through study completion, Day 60
Other	Proportion of subjects alive and free of respiratory failure or extracorporeal membrane oxygenation (ECMO)).	Alive and free of respiratory failure is defined as being alive without the need for invasive mechanical ventilation, non-invasive ventilation, high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen = 0.5), or extracorporeal membrane oxygenation (ECMO).	Through study completion, Day 60
Other	Hierarchical Alive and Ventilator Free (AVF) score.	To compute AVF, each subject is compared to every other subject in both trial arms and assigned a score (win=+1; lose=-1; tie=0) for each pairwise comparison, based on which fared better.	Through study completion, Day 60
Other	Time to recover gas exchange	Length of time is defined as the number of hour to recover gas exchange to PaO2/FiO2 ³ 300 for at least 24 hours.	Up to Day 28
Other	Change in Short Form 36 Health Survey Questionnaire (SF-36).	The short form 36 health survey questionnaire (SF-36)18 measures health perception. The lowest score of 0 indicates unhealthy, where as the highest score of 100 indicates healthy.	Days 9 through 60
Other	Change in Euro Quality of Life Health Survey (EQ-5D-5L).	The EuroQOL health survey instrument (EQ-5D-5L)18 is a five-dimensional five-level generic measure designed to measure and value health status. A Level 1 score indicates no problems. A Level 5 score indicates unable to/extreme problems.	Days 9 through 60
Other	Peak plasma concentration (Cmax) for GEn-1124 and its metabolites.		Days 1 through 6
Other	Terminal elimination rate constant (Kel) and half-life (T1/2) in plasma for GEn-1124 and its metabolites.		Days 1 through 6
Other	Area under the plasma concentration versus time curve (AUC) for GEn-1124 and its metabolites.		Days 1 through 6
Other	Plasma volume of distribution (Vss) for GEn-1124 and its metabolites.		Days 1 through 6
Other	Plasma Clearance (CL) for GEn-1124 and its metabolites.		Days 1 through 6
Other	Plasma concentration at steady state (Css) for GEn-1124 and its metabolites.		Days 1 through 6
Other	Measure protein biomarkers in whole blood.	Protein biomarkers including TNFalpha, IL6 and IL1beta, IL10 and HSP27 will be measured by Olink's arbitrary unit, Normalized Protein eXpression (NPX), which is in Log2 scale.	Days 1 through 6
Other	Measure protein biomarkers in bronchoalveolar lavage (BAL) fluid.	Protein biomarkers including TNFalpha, IL6 and IL1beta, IL10 and HSP27 will be measured by Olink's arbitrary unit, Normalized Protein eXpression (NPX), which is in Log2 scale.	Days 1 through 6
Other	Measure protein biomarkers in tracheal aspirate (TA).	Protein biomarkers including TNFalpha, IL6 and IL1beta, IL10 and HSP27 will be measured by Olink's arbitrary unit, Normalized Protein eXpression (NPX), which is in Log2 scale.	Days 1 through 6
Primary	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

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