COVID
Conditions
Keywords
IMMUNOMODULATORY MESENCHYMAL STEM CELLS, MSC, COVID-19, Mechanical ventilation, Severe respiratory distress
Brief summary
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.
Interventions
BIOLOGICALBM-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-.
BIOLOGICALPlacebo
plasmalyte and human albumin
Sponsors
ImmunityBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Within 30 Days of Randomization | 30 days | Incidence of AEs within 30 days of randomization. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BM-Allo.MSC Subjects in the experimental arm will be administered BM-Allo.MSC
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-. | 3 |
| Placebo Subjects in the control arm will be treated with placebo
Placebo: plasmalyte and human albumin | 1 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 1 |
Baseline characteristics
| Characteristic | BM-Allo.MSC | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 8.5 | 62.8 years STANDARD_DEVIATION 6.99 | 64.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
| Subjects with severe disease requiring ventilator support during COVID-19 infection | 3 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 1 / 1 |
| other Total, other adverse events | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 3 / 3 | 1 / 1 |
Outcome results
Primary
Number of Participants With Adverse Events Within 30 Days of Randomization
Incidence of AEs within 30 days of randomization.
Time frame: 30 days
Population: Analysis population is all randomized subjects who received at least one dose of study intervention (safety analysis population)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BM-Allo.MSC | Number of Participants With Adverse Events Within 30 Days of Randomization | 3 Participants |
| Placebo | Number of Participants With Adverse Events Within 30 Days of Randomization | 1 Participants |