Study of FT516 for the Treatment of COVID-19 in Hospitalized Patients With Hypoxia

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Completed

CT.gov ID

NCT04363346

Collaborator

(none)

Enrollment

Location

Arms

9.2

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase I study with the primary objective of identifying the maximum tolerated dose (MTD) of FT516 using 3 dose-escalation strategies (number of doses and cell dose) for the treatment of coronavirus disease 2019 (COVID-19). This study provides initial estimates of safety and efficacy based on stable respiratory function, as well as, determining the feasibility for full-scale studies designed both for efficacy and safety.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: FT516	Phase 1

Detailed Description

Given the urgency of COVID-19 and the known anti-viral activity of natural killer (NK) cells, this clinical trial uses immediately available off-the-shelf induced pluripotent stem cell (iPSC) derived NK cells already being used to treat cancer patients.

FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation. The investigators expect that natural developing anti-COVID IgG (early data suggest that some develop in 7-10 days after diagnosis) will enhance targeting of FT516 to infected cells.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

The study starts with a fast-track design by proceeding in cohorts of one patient until the first DLT is observed. If no DLT is observed, escalation continues by one patient per cohort until Dose Strategy 3 is reached. If the MTD is not yet established by Dose Strategy 3, Dose Strategy 3 is expanded to 6 patients using the final stage of a "3+3" design. An extension of 4 additional patients is planned if FT516 continues to be safe for a total of 10 patients treated at the MTD.The study starts with a fast-track design by proceeding in cohorts of one patient until the first DLT is observed. If no DLT is observed, escalation continues by one patient per cohort until Dose Strategy 3 is reached. If the MTD is not yet established by Dose Strategy 3, Dose Strategy 3 is expanded to 6 patients using the final stage of a "3+3" design. An extension of 4 additional patients is planned if FT516 continues to be safe for a total of 10 patients treated at the MTD.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of FT516 Safety and Feasibility for the Treatment of Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients With Hypoxia

Actual Study Start Date :

May 14, 2020

Actual Primary Completion Date :

Feb 18, 2021

Actual Study Completion Date :

Feb 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Strategy 1 Dose Strategy 1: Day 1 - FT516 is given at 9x107 cells/dose (low)	Drug: FT516 FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation.
Experimental: Dose Strategy 2 Dose Strategy 2: Day 1 - FT516 is given at 9x107 cells/dose (low) + Day 4 - FT516 is given at 3x108 cells/dose (mid)	Drug: FT516 FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation.
Experimental: Dose Strategy 3 Dose Strategy 3: Day 1 - FT516 is given at 9x107 cells/dose (low) + Day 4 - FT516 is given at 3x108 cells/dose (mid) + Day 7 - FT516 is given at 9x108 cells/dose (high)	Drug: FT516 FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation.

Arm

Intervention/Treatment

Experimental: Dose Strategy 1

Dose Strategy 1: Day 1 - FT516 is given at 9x107 cells/dose (low)

Drug: FT516

Experimental: Dose Strategy 2

Dose Strategy 2: Day 1 - FT516 is given at 9x107 cells/dose (low) + Day 4 - FT516 is given at 3x108 cells/dose (mid)

Drug: FT516

Experimental: Dose Strategy 3

Dose Strategy 3: Day 1 - FT516 is given at 9x107 cells/dose (low) + Day 4 - FT516 is given at 3x108 cells/dose (mid) + Day 7 - FT516 is given at 9x108 cells/dose (high)

Drug: FT516

Outcome Measures

Primary Outcome Measures

Number of participants with Dose Limiting Toxicity Events [within 7 days after the last dose of FT516]
An accelerated (fast-track) design will continue until first DLT is observed or the maximum Tolerated Dose (MTD) is determined. DLT is defined as any treatment emergent toxicity within 7 days after the last dose of FT516 meeting one of the following criteria based on CTCAE v5: Grade 3 or greater infusion related reaction following FT516 infusion Any new or worsening Grade 3 and any Grade 4 adverse events with the exception of the following known complications of COVID-19: Grade 3 gastrointestinal disorders (diarrhea) Grade 3 hepatic investigations (ALT increased, AST increased) Grade 3 leukopenia/lymphopenia Respiratory deterioration between the 1st dose and 7 days after the last dose of FT516 defined as the need for any type of assisted ventilation (invasive or non-invasive including BiPAP) or oxygen delivery device intended to deliver ≥60% FiO2 (including non-rebreather mask or >10L by simple facemask) to maintain an SpO2 >88%.

Secondary Outcome Measures

The time in days from the 1st FT516 infusion to the elimination of viral shedding in nasal pharyngeal and stool samples [36 days]
The time in days from the 1st FT516 infusion to discontinued need for supplemental oxygen [36 Days]
The time in days from the 1st FT516 infusion to hospital discharge [36 Days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 76 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay.
Requires hospitalization and meets the following:
Radiographic infiltrates by imaging (chest x-ray, CT scan)
Able to maintain Sp02 ≥ 93% oxygen supplementation to a maximum 4L by low flow O2-delivery device at rest
IL-6 level ≥40 pg/ml but <150 pg/mL OR CRP ≥40 mg/L (4 mg/dL) but <150 mg/L (15 mg/dL)
Ferritin < 1000 ng/mL
HCT-CI score of 4 or less - For this score, if PFTs results are not available, any patient requiring oxygen prior to COVID-19 illness is not eligible
Report of usual daily activity level (before COVID-19 illness) of Karnofsky ≥70%
≥ 18 years of age, but < 76 years at time of consent signing
Females of child-bearing potential and males with partners of child-bearing potential must agree to use highly effective contraception from the time of consent and for at least 3 months after the last dose of FT516
Agrees to and signs the separate consent for up to 15 years of follow-up on a separate LTFU companion study (IDIM-2020-28770)
Voluntary written consent prior to the performance of any research related procedures

Exclusion Criteria:

Any medical condition or clinical laboratory abnormality that per Investigator judgement precludes safe participation in and completion of the study, or which could affect compliance with protocol conduct or interpretation of results.
Need for higher-percentage oxygen delivery device (face mask, oxymizer, nonrebreather, venti-mask or pressure support with CPAP/BiPAP)
Patients with adequate oxygenation on room air
Receiving concomitant COVID-19 directed therapy (drugs may be stopped to make patients eligible)
Known allergy to the following FT516 components: albumin (human) or DMSO
Any known condition that requires systemic immunosuppressive therapy (> 5mg prednisone daily or equivalent) topical and inhale steroids are permitted
Active autoimmune disease requiring systemic immunosuppressive therapy
History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible)
Known history of HIV positivity
Pregnant or breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator: Dr.Joshua Rhein, MD, Department of Medicine, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Masonic Cancer Center, University of Minnesota

ClinicalTrials.gov Identifier:

NCT04363346

Other Study ID Numbers:

IDIM-2020-28708
2020LS083

First Posted:

Apr 27, 2020

Last Update Posted:

Apr 5, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Masonic Cancer Center, University of Minnesota

COVID-19

Corona Virus

SARS-COV-2

Additional relevant MeSH terms:

COVID-19

Hypoxia

Study Results

No Results Posted as of Apr 5, 2022