Evaluate the Safety of agenT-797 in Participants With Moderate to Severe Difficulty Breathing Secondary to SARS-CoV-2

Study Overview
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Brief Summary
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A Phase 1/2 study of agenT-797 to treat moderate to severe acute respiratory distress syndrome (ARDS) secondary to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza.

Detailed Description
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This is a Phase 1/2 study to evaluate the safety and potential efficacy of agenT-797, an unmodified, allogeneic invariant natural killer T (iNKT) cell therapy, in participants with moderate to severe ARDS secondary to SARS-CoV-2 or influenza, either with intubation or at high risk to be intubated, as determined using Berlin definition(s). Part 1 will employ a standard 3+3 dose escalation design of agenT-797. All participants will receive a single infusion of agenT-797. Participants will also receive other treatments and supportive care per discretion of the investigator. Once the maximum tolerated dose of agenT-797 has been cleared in Part 1, an Expansion Cohort will be opened. A safety monitoring committee will be established to assess safety and decide on escalation to next cohort and expansion dose, as well as any protocol modification to include less severe cases.

Official Title
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A Phase 1/2 Study of agenT-797 to Treat Moderate to Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2 or Influenza

Conditions
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Respiratory Distress Syndrome, Adult

Intervention / Treatment
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* Drug: agenT-797


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily agree to participate and can provide informed consent or have a duly appointed health care proxy establish which/who has the authority to consent on behalf of the participant Inpatient hospitalization Evidence of SARS-CoV-2 infection with the diagnosis of moderate to severe ARDS secondary to SARS-CoV-2 or influenza per Berlin definition (ARDS 2012) Participants, or study participant's duly appointed health care proxy with the authority to consent on behalf of the participant, must consent to placement of a central venous access line for the administration of agenT-797 Exclusion Criteria: Currently participating and receiving study therapy of an investigational agent that is not registered for any other indication Clinically significant cardiomyopathy Pre-existing respiratory disease, such as significant chronic obstructive pulmonary disease requiring home oxygen, hospitalization, or systemic steroid use during the past year Significant pulmonary hypertension, defined as mean pulmonary artery pressure ≥ 20 millimeters of mercury and evidence of right ventricular dysfunction or enlargement Receipt of vaccines containing live virus within 4 weeks prior to first dose of study treatment Known hypersensitivity to donor-derived cell therapy or their preservation solution Active systemic bacterial or fungal infection or viral co-infection Pregnant or lactating women Presence of multiorgan dysfunction syndrome; no organ failure should be seen other than the organ of interest, which is the lung

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dosage and Cohorts<br>Cohort 1: 100 × 10^6 iNKT cells; Cohort 2: 300 × 10^6 iNKT cells; Cohorts 3 to 4: 1000 × 10^6 iNKT cells Dosage Frequency and Mode of Administration: agenT-797 will be administered to hospitalized participants as a single intravenous infusion. | Drug: agenT-797<br>* agenT-797 is an off-the-shelf cell therapy consisting of ≥ 95% allogeneic human unmodified iNKT cells isolated from 1 healthy donor mononuclear cell apheresis unit and expanded ex vivo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants With Treatment-emergent Adverse Events |  | Baseline through Month 6 | 
| Number Of Participants With Dose-limiting Toxicities |  | Baseline through Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time To Extubation |  | Up to Day 30 | 
| Mean Daily Sequential Organ Failure Assessment Score |  | Day 30 | 
| Change From Baseline In C-reactive Protein | C-reactive protein levels will be used to assess cytokine release syndrome. | Baseline through Day 30 (every 12 hours, as feasible) | 
| Decay In Quantitative Viral Burden From Upper And Lower Respiratory Tract Samples |  | Day 30 | 
| Time From Dosing To Viral Clearance |  | Up to Day 30 | 
| Number Of Participants Experiencing Viral Reactivation And Fungal Infections | This outcome measure will determine if iNKT cells prevent reactivation of other viruses (cytomegalovirus, human papillomavirus, herpes simplex virus, Epstein-Barr virus) and fungal infections. | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Influenza