NCT04399889

Brief Summary

This is a 50 patient, Phase 1/2a multi-center pilot study to test the safety and to describe the preliminary efficacy of intravenous administration of allogenic human cord tissue mesenchymal stromal cells (hCT-MSC) as an investigational agent, under U.S. INDs 19968 (Duke) and 19937 (U Miami) to patients with acute respiratory distress syndrome (ARDS) due to COVID-19 infection (COVID-ARDS). The first 10 consecutive patients will receive investigational MSCs manufactured by Duke. In the second phase of the study, 40 additional patients will be randomized to receive placebo or investigational MSCs manufactured by Duke or University of Miami. Patients will be eligible for infusion of 3 daily consecutive doses of hCT-MSC or placebo if they have a confirmed diagnosis of COVID-19 and meet clinical and radiographic criteria for ARDS. Results from the first 10 patients will be compared with concurrent outcomes utilizing standard of care treatments in participating hospitals and in published reports in the medical literature. Results from the additional 40 patients will be combined with the first 10 and analyzed. The trial is relying on focused eligibility of the participants (patients with ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical outcome (survival, improvement of ARDS). This is a sequential design in the sense that after the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety Monitoring Board whether to proceed with the exploratory randomized portion of the study.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2020

Geographic Reach
1 country

5 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 21, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 22, 2020

Completed
27 days until next milestone

Study Start

First participant enrolled

June 18, 2020

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 16, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 16, 2022

Completed
10 months until next milestone

Results Posted

Study results publicly available

December 20, 2022

Completed
Last Updated

December 20, 2022

Status Verified

November 1, 2022

Enrollment Period

1.7 years

First QC Date

May 21, 2020

Results QC Date

October 24, 2022

Last Update Submit

November 29, 2022

Conditions

Keywords

COVIDCoronavirus infectionCOVID19Covid ARDSAcute Respiratory Distress SyndromeARDS

Outcome Measures

Primary Outcomes (3)

  • Number of Infusion Reactions

    Number of infusion reactions measured by any one of the following: fever, anaphylaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.

    24 hours

  • Number of Delayed Reactions

    Number of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other delayed symptoms associated with infusion of the investigational product.

    28 days

  • Number of Participants With Formation of New Anti-HLA Antibodies

    Number of participants who form new anti-HLA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.

    28 days

Secondary Outcomes (6)

  • Time to Recovery

    up to 90 days

  • Number of Participants With an Increase in PaO2/FiO2 Ratio

    4 days after MSCs

  • Days to Hospital Discharge to Home

    90 days

  • Number of Ventilator Free Days

    90 days

  • Number of Oxygen-free Days

    28 days

  • +1 more secondary outcomes

Study Arms (3)

Open Label infusion of hCT-MSC

EXPERIMENTAL

The first 10 consecutive patients will all receive investigational product.

Biological: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.

Randomized infusion of hCT-MSC

EXPERIMENTAL

An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo. The investigational product will be further randomized to the MSCs manufactured by Duke or University of Miami. These products are considered to be comparable.

Biological: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.

Randomized infusion of Placebo

PLACEBO COMPARATOR

An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo

Other: Placebo

Interventions

Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.

Also known as: hCT-MSC
Open Label infusion of hCT-MSCRandomized infusion of hCT-MSC
PlaceboOTHER

Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.

Randomized infusion of Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • The patient or legally authorized representative (LAR) must have the ability to understand and the willingness to provide a signed and dated informed consent form.
  • Age 18 years and over
  • The patient agrees to use adequate contraception for the duration of the treatment protocol and for 6 months post treatment.
  • Positive RT- PCR testing for COVID-19 nucleic acid using nasopharyngeal swabbing or any other site
  • Patient meets ARDS criteria and is on non-invasive or mechanical ventilation or high flow nasal cannula
  • bilateral opacities on chest imaging consistent with pulmonary edema
  • A need for positive pressure ventilation or high flow nasal cannula
  • PaO2/FiO2 ratio ≤ 300 mmHg by arterial blood gas or SpO2/FiO2 imputation.
  • Infiltrates not fully explained by cardiac failure or fluid overload in the physician's best clinical judgement
  • Subjects requiring dialysis as a result of a COVID-19 infection will not be excluded.

You may not qualify if:

  • Evidence of multiorgan failure involving one or more organs, excluding the lungs as defined below:
  • Presence of shock, defined as MAP \< 65 mmHg with signs of peripheral hypoperfusion, or continuous infusion of 2 or more vasopressor or inotrope agents to maintain MAP ≥ 65 mmHg.
  • Serum bilirubin \> 10 mg/dl
  • Platelet count \< 50,000/ml
  • Subjects requiring dialysis as a result of anything other than a COVID-19 infection will be excluded
  • Evidence of acquired or congenital immunodeficiency (due to immunosuppressive therapy excluding steroid use for treatment of COVID-19 acute respiratory failure, HIV, previous treatment for cancer, etc.)
  • History of metastatic cancer diagnosis or treatment in the past 1 year
  • History of previous treatments with MSCs or other cell therapies
  • Patient is co-enrolled in any other IND-sponsored clinical trials for COVID-19 or ARDs. Drugs that are administered under emergency use authorizations (EUA) by the FDA are permitted.
  • Evidence of pregnancy or lactation
  • Moribund patient not expected to survive \>24 hours
  • Unable/unwilling to deliver lung protective ventilation
  • Patient is receiving Extracorporeal Membrane Oxygenation (ECMO)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke Hospital

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Coronavirus InfectionsCOVID-19Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Coronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesInfectionsPneumonia, ViralPneumoniaRespiratory Tract InfectionsLung DiseasesRespiratory Tract DiseasesRespiration Disorders

Results Point of Contact

Title
Emily Poehlein, MB
Organization
Duke University

Study Officials

  • Joanne Kurtzberg, MD

    Duke Health

    PRINCIPAL INVESTIGATOR
  • Lingye Chen, MD

    Duke Health

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Jerome S. Harris Distinguished Professor of Pediatrics

Study Record Dates

First Submitted

May 21, 2020

First Posted

May 22, 2020

Study Start

June 18, 2020

Primary Completion

February 16, 2022

Study Completion

February 16, 2022

Last Updated

December 20, 2022

Results First Posted

December 20, 2022

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will not share

Locations