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

Sponsor

MiNK Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT04582201

Collaborator

(none)

Enrollment

Locations

Arm

20.3

Actual Duration (Months)

6.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Adult	Drug: agenT-797	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 21, 2020

Actual Primary Completion Date :

Jun 2, 2022

Actual Study Completion Date :

Jun 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dosage and Cohorts 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 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.

Arm

Intervention/Treatment

Experimental: Dosage and Cohorts

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

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.

Outcome Measures

Primary Outcome Measures

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

Time To Extubation [Up to Day 30]
Mean Daily Sequential Organ Failure Assessment Score [Day 30]
Change From Baseline In C-reactive Protein [Baseline through Day 30 (every 12 hours, as feasible)]
C-reactive protein levels will be used to assess cytokine release syndrome.
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 [Day 30]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint John's Cancer Institute	Santa Monica	California	United States	90404
2	Norton Cancer Institute, St. Matthews Campus	Louisville	Kentucky	United States	40207
3	Weill Cornell Medicine New York Presbyterian	New York	New York	United States	10022