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Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Longeveron Mesenchymal Stem Cells (LMSCs) (RECOVER) (RECOVER)

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ClinicalTrials.gov Identifier: NCT04629105
Recruitment Status : Recruiting
First Posted : November 16, 2020
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
Longeveron LLC

Tracking Information
First Submitted Date  ICMJE September 29, 2020
First Posted Date  ICMJE November 16, 2020
Last Update Posted Date November 16, 2020
Actual Study Start Date  ICMJE July 24, 2020
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 12, 2020)
  • Incidence of Treatment-Emergent Serious Adverse Events [ Time Frame: Within 4 weeks after treatment ]
    Incidence of treatment-emergent serious adverse events (TE-SAEs) within 4 weeks after treatment, defined as one or more of the following untoward medical occurrences happening within the first 4 weeks after treatment. i. Life-threatening event (e.g., stroke or non-fatal pulmonary embolism). ii. Event requiring inpatient hospitalization or prolongation of existing hospitalization (e.g., for worsening dyspnea). iii. Event resulting in persistent or significant disability/incapacity. iv. Event resulting in death. v. Event leading to other clinically significant untoward laboratory test result(s) or medical condition(s), as determined by the Investigator.
  • Number of Participants with Abnormal Clinical Significant Laboratory Values in Hematology. [ Time Frame: Baseline to 6 Months ]
    Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.
  • Number of Participants with Changes in Echocardiography Overall Assessment [ Time Frame: Baseline to 6 Months ]
    Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 months, this change in overall assessment will be the outcome in numbers of particants with a change.
  • Number of Participants with Changes to overall assessment of Electrocardiogram [ Time Frame: Baseline to 6 Months ]
    Number of Participants with changes to Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 Months
  • Time to recovery of Sp02 [ Time Frame: Baseline to 6 Months ]
    Time to recovery of Sp02 to 90% or higher on room air (or the oxygen concentration the patient had before acute illness) after 10 minutes of spontaneous breathing.
  • Number of Participants with Abnormal Clinical Significant Lab Values in the Blood Chemistry testing. [ Time Frame: Baseline to 6 months ]
    Number of Participants with Abnormal Clinical Significant Lab Values in Blood Chemistry testing will be assessed at Baseline and 6 Months.
  • Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation. [ Time Frame: Baseline to 6 months ]
    Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation testing will be assessed at Baseline and 6 Months.
  • Number of Participants with Abnormal Clinical Significant Lab Values in the Urinalysis [ Time Frame: Baseline to 6 months ]
    Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2020)
  • Immunity [ Time Frame: Baseline to 6 Months ]
    Geometric mean titer
  • Change in Imaging via X-ray [ Time Frame: Baseline to 6 Months ]
    Change in overall assessment via Lung imaging via chest X-ray will be assessed and compared between baseline and 6 months
  • Change in Imaging via Computerized Tomography [ Time Frame: Baseline to 6 Months ]
    Change in overall assessment via Lung imaging via computerized tomography will be assessed and compared between baseline and 6 months
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Longeveron Mesenchymal Stem Cells (LMSCs) (RECOVER)
Official Title  ICMJE A Phase 1 Double-blinded, Randomized, Placebo-controlled Study for COVID-19 and Influenza Virus-Elicited Acute Respiratory Distress Syndrome (ARDS) Using Longeveron Mesenchymal Stem Cells (LMSCs)
Brief Summary A Phase I, double- blinded, randomized, placebo- controlled study to test the safety of LMSCs in Adults suffering from mild to severe acute respiratory distress syndrome (ARDS) due to COVID-19 resultant from 2019-nCoV coronavirus infection, or resultant from influenza virus infection.
Detailed Description

Double-blinded, randomized, placebo-controlled study with 2 cohorts.

Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. Arm 1: 25 subjects treated with up to 3 doses of 100 million LMSCs. Arm 2: 10 subjects treated with up to 3 doses of Placebo.

Cohort 2: Subjects with ARDS and acutely infected with influenza virus. Arm 3: 25 subjects treated with up to 3 doses of 100 million LMSCs. Arm 4: 10 subjects treated with up to 3 doses of Placebo.

Each subject will be intravenously infused with 100 million LMSCs or placebo on Day 0. If no treatment-related AEs are seen after the infusion, a second infusion will be given on Day 3. If no treatment-related AEs are seen after the second infusion, a third infusion will be given Day 6.

Follow-up visits will be conducted: daily until hospital discharge; at Week 4 after treatment (with LMSCs or placebo) for patients already discharged; and at Month 6 after treatment (with LMSCs or placebo).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double-blinded, randomized, placebo-controlled study with 2 cohorts.

Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. Arm 1: 25 subjects treated with up to 3 doses of 100 million LMSCs. Arm 2: 10 subjects treated with up to 3 doses of Placebo.

Cohort 2: Subjects with ARDS and acutely infected with influenza virus. Arm 3: 25 subjects treated with up to 3 doses of 100 million LMSCs. Arm 4: 10 subjects treated with up to 3 doses of Placebo.

Each subject will be intravenously infused with 100 million LMSCs or placebo on Day 0. If no treatment-related AEs are seen after the infusion, a second infusion will be given on Day 3. If no treatment-related AEs are seen after the second infusion, a third infusion will be given Day 6.

Follow-up visits will be conducted: daily until hospital discharge; at Week 4 after treatment (with LMSCs or placebo) for patients already discharged; and at Month 6 after treatment (with LMSCs or placebo).

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • ARDS, Human
  • Covid19
Intervention  ICMJE
  • Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
    Longeveron Mesenchymal Stem Cells (LMSCs)
  • Other: Placebo
    Placebo
Study Arms  ICMJE
  • Active Comparator: Cohort 1 (SARS-CoV-2): Arm 1 (LMSCs)
    Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. Arm 1: 25 subjects treated with up to 3 doses of 100 million LMSCs.
    Intervention: Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
  • Placebo Comparator: Cohort (SARS-CoV-2): Arm 2 (Placebo)
    Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. Arm 2: 10 subjects treated with up to 3 doses of Placebo.
    Intervention: Other: Placebo
  • Active Comparator: Cohort 2 (Flu): Arm 3 (LMSCs)
    Cohort 2: Subjects with ARDS and acutely infected with influenza virus. Arm 3: 25 subjects treated with up to 3 doses of 100 million LMSCs.
    Intervention: Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
  • Placebo Comparator: Cohort 2 (Flu): Arm 4 (Placebo)
    Cohort 2: Subjects with ARDS and acutely infected with influenza virus. Arm 4: 10 subjects treated with up to 3 doses of Placebo.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 12, 2020)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2025
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female or any race or ethnicity.
  2. At least 18 years of age.
  3. Provide written informed consent. For subjects who are incapable of providing informed consent, written informed consent can be provided on behalf of the subject by a legally authorized representative (LAR).
  4. Diagnosis of mild to severe ARDS per the Berlin Definition of ARDS. More specifically, the following 3 conditions must be present.

    1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio < 200 with at least 8 cm H2O positive end-expiratory airway pressure (PEEP). A patient may be included if the PaO2/FiO2 ratio < 200 with < 8 cm H2O PEEP if there is a contraindication to increased PEEP (evidence of barotrauma).
    2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph.
    3. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates.
  5. Confirmed diagnosis of infection with coronavirus or influenza virus.
  6. Willing to perform all assessments required for the study.
  7. Must agree to the collection of all blood samples per protocol.
  8. Must agree to have samples stored and used for secondary research.

Exclusion Criteria:

  1. Patient receiving Extracorporeal Membrane Oxygenation (ECMO).
  2. History of malignancy within previous 2.5 years, except for curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ, or cervical carcinoma.
  3. Prior positive test for any of the following without demonstration of resolution.

    i. Hepatitis B virus (HBV) surface antigen (HBsAg). ii. Viremic hepatitis C virus (HCV). iii. Human immunodeficiency virus-1 or -2 (HIV1 or 2 HIV2). iv. Human T-cell leukemia virus-I or -II (HTLV-I or HTLV-II). v. Syphilis.

  4. Female who is pregnant, nursing, or of childbearing potential while not practicing effective contraception.
  5. Known hypersensitivity to dimethyl sulfoxide (DMSO).
  6. Be an organ transplant recipient, other than for corneal, bone, skin, ligament, or tendon transplant.
  7. Actively listing (or expected listing) for transplant of any organ, other than for corneal, bone, skin, ligament, or tendon transplant.
  8. Continuous use of any medication at immunosuppressive dosing for greater than 14 consecutive days over the past 3 months.
  9. Currently participating in an investigational therapeutic or device trial, or have participated in an investigational therapeutic or device trial within the previous 30 days, or participate in any other clinical trial for the duration of the time that the subject actively participates in this trial. However, use of hydroxychloroquine, remdesivir, lopinavir/ritonavir and ivermectin are allowed as well as convalescent plasma.. Exceptions for other experimental interventions related to treating the patient's acute illness may be made with prior approval of Longeveron.
  10. Any serious comorbid illness or any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study, or that may compromise the validity of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kevin N Ramdas, MD, MPH 786-769-4935 kramdas@longeveron.com
Contact: Anthony Oliva, PhD 305-909-0838 aoliva@longeveron.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04629105
Other Study ID Numbers  ICMJE 00-006
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  ICMJE Not Provided
Responsible Party Longeveron LLC
Study Sponsor  ICMJE Longeveron LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Longeveron LLC
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP