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

• ClinicalTrials.gov Identifier: NCT04397796
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2020
• Last Update Posted: February 1, 2022
• Sponsor: ImmunityBio, Inc.
• Information provided by (Responsible Party): ImmunityBio, Inc.

Tracking Information

• First Submitted Date: May 18, 2020
• First Posted Date: May 21, 2020
• Last Update Posted Date: February 1, 2022
• Actual Study Start Date: August 3, 2020
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 19, 2020)

• Incidence of AEs [ Time Frame: 30 days ]
  Incidence of AEs within 30 days of randomization.
• Mortality [ Time Frame: 30 days ]
  Mortality within 30 days of randomization.
• Death [ Time Frame: 30 days ]
  Cause of death within 30 days of randomization
• Number of ventilator-free days [ Time Frame: 60 days ]
  Number of ventilator-free days within 60 days of randomization.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 19, 2020)

• Improvement of one category [ Time Frame: 30 days ]
  Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows:

  1. Death
  2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
  3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
  4. Hospitalized, requiring supplemental oxygen
  5. Hospitalized, not requiring supplemental oxygen
  6. Not hospitalized, limitation on activities
  7. Not hospitalized, no limitations on activities
• 7-point ordinal scale [ Time Frame: 30 days ]
  Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows:

  1. Death
  2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
  3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
  4. Hospitalized, requiring supplemental oxygen
  5. Hospitalized, not requiring supplemental oxygen
  6. Not hospitalized, limitation on activities
  7. Not hospitalized, no limitations on activities
• NEWS [ Time Frame: 30 days ]
  Change in NEWS from baseline. The following 7 clinical parameters will be assessed:

  1. Respiration rate
  2. Oxygen saturation
  3. Any supplemental oxygen
  4. Temperature
  5. Systolic blood pressure
  6. Heart rate
  7. 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.
• NEWS of ≤ 2 [ Time Frame: 30 days ]
  Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.
• Sequential Organ Failure Assessment (SOFA) [ Time Frame: days 8, 15, 22, and 29 ]
  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:

  1. Respiration
  2. Coagulation
  3. Liver
  4. Cardiovascular
  5. Central Nervous System
  6. Renal
• Oxygen [ Time Frame: 30 days ]
  Number of days requiring oxygen.
• Hospitalization [ Time Frame: 30 days ]
  Duration of hospitalization from randomization.
• Incidence of SAEs [ Time Frame: 30 days ]
  Incidence of SAEs within 30 days of randomization

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Safety of Therapeutic Tx With Immunomodulatory MSC in Adults With COVID-19 Infection Requiring Mechanical Ventilation
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: COVID

Intervention

• 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-.
• Biological: Placebo
  plasmalyte and human albumin

Study Arms

• Experimental: BM-Allo.MSC
  Subjects in the experimental arm will be administered BM-Allo.MSC
  Intervention: Biological: BM-Allo.MSC
• Placebo Comparator: Placebo
  Subjects in the control arm will be treated with placebo
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 19, 2020): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2022
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04397796
• Other Study ID Numbers: QUILT-COVID-19-MSC
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ImmunityBio, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ImmunityBio, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ImmunityBio, Inc.
• Verification Date: February 2022