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Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Lomecel-B (RECOVER) (RECOVER)

Primary Purpose

ARDS, Human, Covid19

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Longeveron Mesenchymal Stem Cells (LMSCs)
Placebo
Sponsored by
Longeveron Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ARDS, Human

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Miami VA Healthcare System
  • University of Maryland Medical Center
  • Wake Forest Baptist Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

Cohort 1 (SARS-CoV-2): Arm 1 (LMSCs)

Cohort (SARS-CoV-2): Arm 2 (Placebo)

Cohort 2 (Flu): Arm 3 (LMSCs)

Cohort 2 (Flu): Arm 4 (Placebo)

Arm Description

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.

Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. 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.

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

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Serious Adverse Events
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.
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
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
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 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.
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.
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
Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.

Secondary Outcome Measures

Immunity
Geometric mean titer
Change in Imaging via X-ray
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
Change in overall assessment via Lung imaging via computerized tomography will be assessed and compared between baseline and 6 months

Full Information

First Posted
September 29, 2020
Last Updated
October 2, 2023
Sponsor
Longeveron Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04629105
Brief Title
Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Lomecel-B (RECOVER)
Acronym
RECOVER
Official Title
A Phase 1 Double-blinded, Randomized, Placebo-controlled Study for COVID-19 and Influenza Virus-Elicited Acute Respiratory Distress Syndrome (ARDS) Using Lomecel-B
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 24, 2020 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Longeveron Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A Phase I, double- blinded, randomized, placebo- controlled study to test the safety of Lomecel-B 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 Lomecel-B 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 Lomecel-B Arm 4: 10 subjects treated with up to 3 doses of Placebo. Each subject will be intravenously infused with 100 million Lomecel-B (formerly 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ARDS, Human, Covid19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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
ParticipantInvestigator
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 (SARS-CoV-2): Arm 1 (LMSCs)
Arm Type
Active Comparator
Arm Description
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 Title
Cohort (SARS-CoV-2): Arm 2 (Placebo)
Arm Type
Placebo Comparator
Arm Description
Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. Arm 2: 10 subjects treated with up to 3 doses of Placebo.
Arm Title
Cohort 2 (Flu): Arm 3 (LMSCs)
Arm Type
Active Comparator
Arm Description
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 Title
Cohort 2 (Flu): Arm 4 (Placebo)
Arm Type
Placebo Comparator
Arm Description
Cohort 2: Subjects with ARDS and acutely infected with influenza virus. Arm 4: 10 subjects treated with up to 3 doses of Placebo.
Intervention Type
Biological
Intervention Name(s)
Longeveron Mesenchymal Stem Cells (LMSCs)
Intervention Description
Longeveron Mesenchymal Stem Cells (LMSCs)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Serious Adverse Events
Description
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.
Time Frame
Within 4 weeks after treatment
Title
Number of Participants with Abnormal Clinical Significant Laboratory Values in Hematology.
Description
Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.
Time Frame
Baseline to 6 Months
Title
Number of Participants with Changes in Echocardiography Overall Assessment
Description
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.
Time Frame
Baseline to 6 Months
Title
Number of Participants with Changes to overall assessment of Electrocardiogram
Description
Number of Participants with changes to Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 Months
Time Frame
Baseline to 6 Months
Title
Time to recovery of Sp02
Description
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.
Time Frame
Baseline to 6 Months
Title
Number of Participants with Abnormal Clinical Significant Lab Values in the Blood Chemistry testing.
Description
Number of Participants with Abnormal Clinical Significant Lab Values in Blood Chemistry testing will be assessed at Baseline and 6 Months.
Time Frame
Baseline to 6 months
Title
Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation.
Description
Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation testing will be assessed at Baseline and 6 Months.
Time Frame
Baseline to 6 months
Title
Number of Participants with Abnormal Clinical Significant Lab Values in the Urinalysis
Description
Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Immunity
Description
Geometric mean titer
Time Frame
Baseline to 6 Months
Title
Change in Imaging via X-ray
Description
Change in overall assessment via Lung imaging via chest X-ray will be assessed and compared between baseline and 6 months
Time Frame
Baseline to 6 Months
Title
Change in Imaging via Computerized Tomography
Description
Change in overall assessment via Lung imaging via computerized tomography will be assessed and compared between baseline and 6 months
Time Frame
Baseline to 6 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female or any race or ethnicity. At least 18 years of age. 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). Diagnosis of mild to severe ARDS per the Berlin Definition of ARDS. More specifically, the following 3 conditions must be present. 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). Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph. No clinical evidence of left atrial hypertension for bilateral pulmonary infiltrates. Confirmed diagnosis of infection with coronavirus or influenza virus. Willing to perform all assessments required for the study. Must agree to the collection of all blood samples per protocol. Must agree to have samples stored and used for secondary research. Exclusion Criteria: Patient receiving Extracorporeal Membrane Oxygenation (ECMO). History of malignancy within previous 2.5 years, except for curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ, or cervical carcinoma. 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. Female who is pregnant, nursing, or of childbearing potential while not practicing effective contraception. Known hypersensitivity to dimethyl sulfoxide (DMSO). Be an organ transplant recipient, other than for corneal, bone, skin, ligament, or tendon transplant. Actively listing (or expected listing) for transplant of any organ, other than for corneal, bone, skin, ligament, or tendon transplant. Continuous use of any medication at immunosuppressive dosing for greater than 14 consecutive days over the past 3 months. 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. 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.
Facility Information:
Facility Name
Miami VA Healthcare System
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Lomecel-B (RECOVER)

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