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

NCT04363346 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IDIM-2020-287082020LS083
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

COVID-19; Corona Virus; SARS-COV-2

Outcome Measures

Primary Outcomes (1)

• Number of participants with Dose Limiting Toxicity Events

  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%.

  within 7 days after the last dose of FT516

Secondary Outcomes (3)

• 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

Study Arms (3)

Dose Strategy 1

EXPERIMENTAL

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

Drug: FT516

Dose Strategy 2

EXPERIMENTAL

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

Dose Strategy 3

EXPERIMENTAL

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

Interventions

FT516 DRUG

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.

Dose Strategy 1; Dose Strategy 2; Dose Strategy 3

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Dr.Joshua Rhein, MD

  Department of Medicine, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: May 14, 2020
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: April 5, 2022

Record last verified: 2022-04

Locations

US (1)