Study of the Safety of Therapeutic Tx With Immunomodulatory MSC in Adults With COVID-19 Infection Requiring Mechanical Ventilation

Phase 1b Randomized, Double-Blind, Placebo-Controlled Study Of The Safety Of Therapeutic Treatment With Immunomodulatory Mesenchymal Stem Cells In Adults With COVID-19 Infection Requiring Mechanical Ventilation

This is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID
• Intervention / Treatment: Biological: BM-Allo.MSC; Biological: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Lynwood, California, United States, 90262
      • St. Francis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. For subjects that are intubated and/or sedated, or otherwise unable to provide consent, prospective consent from a legally-authorized representative is required. The subject or his/her legally authorized representative must be able to provide consent.
3. Has laboratory-confirmed positive novel coronavirus (SARS-CoV-2) test, as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen < 72 hours prior to enrollment, or meets the criteria to guide the evaluation and testing of patients under investigation (PUI) for COVID-19 (https://emergency.cdc.gov/han/2020/HAN00428.asp).

4. Requiring mechanical ventilatory support with moderate to severe Acute Respiratory Distress Syndrome (ARDS) as determined by the Berlin criteria:

   1. Bilateral opacities present on a chest radiograph or computed tomographic (CT) scan. These opacities are not fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules.
   2. Origin of Edema: Respiratory failure not fully explained by cardiac failure or fluid overload.

   3. Oxygenation: Moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS:

      • Moderate: PaO2/FiO2 >100 mmHg and ≤ 200 mmHg, on ventilator settings that include PEEP ≥ 5 cm H2O
      • Severe: PaO2/FiO2 ≤100 mmHg on ventilator settings that include PEEP ≥5 cm H2O Subjects receiving extracorporeal membrane oxygenation (ECMO) will not be enrolled in this study.
5. High-sensitivity C-reactive Protein (hs-CRP) serum level > 4.0 mg/dL
6. Acute Physiology and Chronic Health Evaluation (APACHE IV) score > 5
7. Agrees to the collection of nasopharyngeal (NP) swabs and venous blood per protocol.
8. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
9. Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception while on study and for at least 1 month after the last dose of BM-Allo.MSC. Non-sterile male subjects must agree to use a condom while on study and for up to 1 month after the dose of BM-Allo.MSC. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), oral contraceptives, and abstinence.

Exclusion Criteria:

1. Known hypersensitivity to any component of the study medication(s).
2. Signs of multisystem organ failure. Liver function tests (LFTs) > 5x normal.
3. Intubated > 72 continuous hours.
4. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
5. Pregnant and nursing women. A negative serum pregnancy test during screening (within 72 hours prior to the first dose) must be documented before MSCs are administered to a female subject of child-bearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BM-Allo.MSC; Subjects in the experimental arm will be administered BM-Allo.MSC	Biological: BM-Allo.MSC; BM-Allo.MSC for Infusion, is manufactured from normal donor derived bone marrow product and are phenotypically CD73+, CD90+, CD105+, and negative for CD14-, CD34-, CD45-, HLA-DR-.
PLACEBO_COMPARATOR: Placebo; Subjects in the control arm will be treated with placebo	Biological: Placebo; plasmalyte and human albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs	Incidence of AEs within 30 days of randomization.	30 days
Mortality	Mortality within 30 days of randomization.	30 days
Death	Cause of death within 30 days of randomization	30 days
Number of ventilator-free days	Number of ventilator-free days within 60 days of randomization.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of one category	Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities; Not hospitalized, no limitations on activities	30 days
7-point ordinal scale	Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities; Not hospitalized, no limitations on activities	30 days
NEWS	Change in NEWS from baseline. The following 7 clinical parameters will be assessed: Respiration rate; Oxygen saturation; Any supplemental oxygen; Temperature; Systolic blood pressure; Heart rate; Level of consciousness Measurements within normal ranges are assigned a 0. If the measurement in each category is substantially above or below the normal range, it is given a +1, +2, or +3. The more far off than normal, the bigger the number (in each category). A higher number indicates worse outcome. Each category can be 0-3, except for supplemental oxygen which is only 0-2. The highest value a patient can get is 20.	30 days
NEWS of ≤ 2	Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.	30 days
Sequential Organ Failure Assessment (SOFA)	Change from baseline in Sequential Organ Failure Assessment (SOFA) score on days 8, 15, 22, and 29. System Score for each category is 0-4 with 28 is the maximum score for worst outcome. The following categories are: Respiration; Coagulation; Liver; Cardiovascular; Central Nervous System; Renal	days 8, 15, 22, and 29
Oxygen	Number of days requiring oxygen.	30 days
Hospitalization	Duration of hospitalization from randomization.	30 days
Incidence of SAEs	Incidence of SAEs within 30 days of randomization	30 days

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2020
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 19, 2020
• First Posted (ACTUAL): May 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; MSC; Mechanical ventilation; IMMUNOMODULATORY MESENCHYMAL STEM CELLS; Severe respiratory distress
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: QUILT-COVID-19-MSC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No