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Allocetra-OTS in COVID-19

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ClinicalTrials.gov Identifier: NCT04513470
Recruitment Status : Active, not recruiting
First Posted : August 14, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Mevorach Dror, Hadassah Medical Organization

Brief Summary:

This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in 5 subjects with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited.

After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below.

Subjects will be hospitalized for COVID-19, and later as medically indicated. Following investigational product (IP) administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days.


Condition or disease Intervention/treatment Phase
COVID-19 Biological: Allocetra-OTS Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Multi-Center, Open-Label Study, Evaluating Safety of Allocetra-OTS for the Prevention of Organ-Failure Deterioration in Severe Patients With COVID-19 and Respiratory Dysfunction
Actual Study Start Date : August 1, 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : February 2021

Arm Intervention/treatment
Experimental: COVID-19
Five subjects, male or female > 18 and < 80-year-old diagnosed with respiratory dysfunction and COVID-19, as defined in the Eligibility Criteria, and treated with a single intravenous dose of Allocetra-OTS investigational product as detailed in the Interventions section.
Biological: Allocetra-OTS
Allocetra-OTS is a cell-based therapeutic composed of donor early apoptotic cells, comprising allogeneic mononuclear enriched cell suspension with at least 40% early apoptotic cells. The suspension is prepared with Ringer's lactate solution and administered IV. It is stored at 2-8°C until 20+25 minutes before infusion and at room temperature thereafter. Each dose contains 140x10E6 ± 20% cells/ kg of recipient body weight (at screening) in a total volume of 375 mL in a transfer pack that undergoes irradiation and is administered via an adjusted filter using a volumetric pump, at a starting rate of 48 mL/hour with a gradual increase every 15-25 minutes of 15 mL/hour to a maximal rate of 102 mL/hour. The study intervention should be completed within 72 hours of completing the manufacturing process. During product administration, no other IV fluids such as Ringer's lactate or normal saline will be given in parallel unless medically indicated due to volume depletion.




Primary Outcome Measures :
  1. Assessment of safety by determining the number of participants with any Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: 28 days follow up ]
    Incidence rates and severity of any Adverse Events (AE) and Serious Adverse Events (SAE)


Secondary Outcome Measures :
  1. Preliminary Efficacy: Recovery from COVID-19 as determined by negative PCR or asymptomatic by the NIH classification for the severity of illness [ Time Frame: 28 days follow up ]

    Recovery from COVID-19 will be determined by the following measures:

    The percentage of subjects reporting to 'Asymptomatic' by the NIH classification and the number of days to reach this classification, and/or The percentage of subjects negative for SARS-CoV-2 RNA (by PCR) and the number of days for viral clearance (negative PCR results)


  2. Mortality [ Time Frame: 28 days follow up ]
    Incidence rate of Mortality from any cause

  3. Preliminary Efficacy: To assess prevention of respiratory deterioration associated with COVID-19 by measuring the PaO2/FiO2 ratio [ Time Frame: On days, 3, 5, 7, 14, and 28 during 28 days follow up ]

    Respiratory function will be assessed by measuring the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2).

    Patients with PaO2/FiO2 ratio < 300mmHg are considered severe patients.

    • The PaO2/FiO2 ratio and its change from the baseline value will be measured on days, 3, 5, 7, 14, and 28.


  4. Hospitalization [ Time Frame: 28 days follow up ]
    Cumulative days in the Intensive care unit (ICU) or COVID-19 ICU or COVID-19 department and/or in hospital.

  5. Life support [ Time Frame: 28 days follow up ]
    Number of ventilator-free days.

  6. Clinical status by the new NIH Patient Classification for the severity of illness [ Time Frame: 28 days follow up ]
    Change from baseline of the new NIH Patient Classification for the severity of illness.

  7. Clinical status by NEWS2 [ Time Frame: 28 days follow up ]
    Change from baseline of National Early Warning Score (NEWS2).

  8. Support measurements: percentage of subjects reporting each severity rating on a 7-point ordinal scale [ Time Frame: 28 days follow up ]

    Percentage of subjects reporting each severity rating on a 7-point ordinal scale at day 28 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.

  9. Support measurements: improvement of severity rating on a 7-point ordinal scale [ Time Frame: 28 days follow up ]

    Time to improvement of one category from admission using this 7-point ordinal scale, 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.

  10. Virus Clearance [ Time Frame: Within the 28 days follow up, tested on days 14 and 28 ]
    Evaluation of clearance of the virus using PCR (Negative for SARS-CoV-2 RNA) on days 14 and 28 (if not negative before).

  11. Exploratory: Serum cytokines/chemokines and immunomodulating factors [ Time Frame: 28 days follow up ]
    Serum concentrations (pg/ml) of cytokines, chemokines, complement, hematopoietic growth factors, and other immunomodulating factors (including HMGB1) will be measured before and after the infusion of Allocetra-OTS and periodically throughout 28 days follow up.

  12. Exploratory: complete blood counts [ Time Frame: 28 days follow up ]
    Differential blood counts will be performed before and after the infusion of Allocetra-OTS and periodically throughout 28 days follow up.

  13. Exploratory: Histone and cell-free DNA levels [ Time Frame: 28 days follow up ]
    Histone and cell-free DNA plasma levels will be measured before and after the infusion of Allocetra-OTS and periodically throughout 28 days follow up.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Five subjects, male or female > 18 and < 80-year-old diagnosed with respiratory dysfunction and COVID-19, as defined below:

  1. Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source.
  2. Patients classified as severe according to NIH severity classification.
  3. All patients will be treated by treating physicians with subcutaneous (S.C.) Clexane, at a minimal dose of 40 mg a day

Exclusion Criteria:

  1. Pregnancy, lactation, and childbearing potential woman who are not willing to use acceptable contraceptives measures for the entire study duration.
  2. Combined with other organ failures (need organ support not including respirator), including Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30)
  3. Patients with malignant tumor, other serious systemic diseases and psychosis.
  4. Patients who are participating in other clinical trials or treated with any experimental agents that may contradict this trial (i.e, biologics)
  5. Co-Infection of HIV, tuberculosis.
  6. Known immunocompromised state or medications known to be immunosuppressive (see concomitant prohibited medications).
  7. Intubated patients (due to inability to sign an informed consent)
  8. Patients with P/F ratio of <150 or a change in status of eligibility manifested by a rapid decline of P/F ratio between eligibility status and actual drug delivery.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04513470


Locations
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Israel
Hadassah Medical Center
Jerusalem, Israel, 91120
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
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Principal Investigator: Dror Mevorach, MD Hadassah Medical Organization
Principal Investigator: Peter V van Heerden, MD Hadassah Medical Organization
Publications:
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Responsible Party: Mevorach Dror, Professor & Head, Department of Internal Medicine B; Head, Rheumatology Research Center, Hadassah and the Hebrew University Medical School, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT04513470    
Other Study ID Numbers: DM003
First Posted: August 14, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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