<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02982915</url>
  </required_header>
  <id_info>
    <org_study_id>00-0000-03</org_study_id>
    <nct_id>NCT02982915</nct_id>
  </id_info>
  <brief_title>Lomecel-B on Vaccine-Specific Antibody- Response in Subjects With Aging Frailty</brief_title>
  <acronym>HERA</acronym>
  <official_title>Effects of Intravenous Delivery of Lomecel-B (Formerly Allogenic Longeveron Human Mesenchymal Stem Cells (LMSCs)) on VaccinE-Specific Antibody Responses in Subjects With Aging Frailty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Longeveron Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Longeveron Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I/II, randomized, blinded and placebo-controlled study to test the safety and&#xD;
      efficacy of Lomecel-B for improving vaccine immune response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A pilot phase will consist of a 3 subject safety run-in, followed by 20 subject randomized&#xD;
      phase to evaluate influenza vaccine response at 1 week and 4 weeks post infusion of Lomecel-B&#xD;
      (Formerly LMSCs). This will be followed by a double-blinded, randomized, placebo-controlled&#xD;
      phase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">September 2022</completion_date>
  <primary_completion_date type="Actual">September 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of any treatment-emergent serious adverse event (TE-SAE), defined as one or more of the following untoward medical occurrences within 30 days after infusion as assessed by the following:</measure>
    <time_frame>30 days after infusion</time_frame>
    <description>Is life-threatening (e.g., stroke or non-fatal pulmonary embolism).&#xD;
Requires inpatient hospitalization or prolongation of existing hospitalization.&#xD;
Results in persistent or significant disability/incapacity.&#xD;
Results in death&#xD;
Results in other clinically significant untoward laboratory test result(s) or medical condition(s), determined per Investigator's judgment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The ability of Lomecel-B (LMSC) treatment to improve inactivation of influenza virus as assessed by validated hemagglutination inhibition (HAI) assays.</measure>
    <time_frame>Baseline Visit, Vaccination Visits, Weeks 1, 2, 4, Month 6 and Month 12 Follow-Up Visits.</time_frame>
    <description>Measurements of validated hemagglutination inhibition (HAI) assays at follow up visits.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline between the LMSC and placebo cohorts as assessed by plasma cytokine levels:</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Plasma levels of interleukins measured in pg/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in rate of decline from Aging Frailty</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in Clinical Frailty rating</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessed by the Falls Efficacy Scale-International and Performance Oriented Mobility Assessment</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in risk of falling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS Short Form 20a questionnaire</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in subject quality of life as assessed by participant-reported outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS Mobility questionnaire</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in subject quality of life as assessed by participant-reported outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS Upper Extremity questionnaire</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in subject quality of life as assessed by participant-reported outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short Form 36 questionnaire</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in subject quality of life as assessed by participant-reported outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IIEF questionnaire</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in subject quality of life as assessed by participant-reported outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SQOL-F questionnaire</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change in subject quality of life as assessed by participant-reported outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death from any cause</measure>
    <time_frame>Within 12 months after infusion</time_frame>
    <description>Number of participants that die from any cause while enrolled on the trial and after being treated with LMSCs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Falls Efficacy Scale-International (FES-I)</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Change by participant-reported outcomes. Minimum 16 (no concern about falling) to maximum 64 (severe concern about falling)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline between the LMSC and placebo cohorts as assessed by B &amp; T cell levels:</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Plasma levels of B &amp; T Cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of decline in Aging Frailty status as assessed by the 6 minute walk test</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Distance in meters walked in 6 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of decline in Aging Frailty status as assessed by the Short Physical Performance Battery (SPPB)</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Short Physical Performance Battery Assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of decline in Aging Frailty status as assessed by the Tinetti POMA Test</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>TInetti POMA assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of decline in Aging Frailty status as assessed by the Weight Loss</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Weigh measurements at visits</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of decline in Aging Frailty status as assessed by the Handgrip Test</measure>
    <time_frame>Baseline, month 6 and month 12 after infusion</time_frame>
    <description>Handgrip strength via dynamometer.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Aging Frailty</condition>
  <arm_group>
    <arm_group_label>Pilot Phase- Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 20 million Longeveron Mesenchymal Stem Cells (LMSCs) will be delivered followed by vaccination with Fluzone High-Dose at 1 week post-infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pilot Phase Cohort B &amp; C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of 100 million Longeveron Mesenchymal Stem Cells (LMSCs) followed by vaccination with Fluzone High-Dose at either 1 week (Cohort B) or 4 weeks (Cohort C) post infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Double-Blind,Randomized,Placebo Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 cohorts to receive a single infusion of 100 million Longeveron Mesenchymal Stem Cells (LMSCs) (Cohort A: 30 subjects) or placebo (Cohort B:30 subjects) followed by vaccination with Fluzone High-Dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Longeveron Mesenchymal Stem Cells (LMSCs)</intervention_name>
    <description>Intravenously delivered</description>
    <arm_group_label>Double-Blind,Randomized,Placebo Phase</arm_group_label>
    <arm_group_label>Pilot Phase Cohort B &amp; C</arm_group_label>
    <arm_group_label>Pilot Phase- Cohort A</arm_group_label>
    <other_name>Lomecel-B</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fluzone High Dose Vaccine</intervention_name>
    <description>Intramuscular injection</description>
    <arm_group_label>Double-Blind,Randomized,Placebo Phase</arm_group_label>
    <arm_group_label>Pilot Phase Cohort B &amp; C</arm_group_label>
    <arm_group_label>Pilot Phase- Cohort A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  be willing and able to provide written informed consent and comply with all procedures&#xD;
             required by the protocol.&#xD;
&#xD;
          -  be 65 - 90 years of age at the time of signing the Informed Consent Form.&#xD;
&#xD;
          -  have a diagnosis of Aging Frailty, with a score of 4 to 7 using the Canadian Frailty&#xD;
             Scale.&#xD;
&#xD;
          -  have a six-minute walk test (6MWT) distance of 200m - 400m for each of 2 trials, and&#xD;
             the 2 trials must be within 15% of each other.&#xD;
&#xD;
          -  have total bilirubin between 0.3 - 1.9 mg/dL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  be unwilling or unable to perform any of the assessments required by the Protocol.&#xD;
&#xD;
          -  score ≤24 on the Mini Mental State Examination (MMSE).&#xD;
&#xD;
          -  have previously received current year's flu-vaccine.&#xD;
&#xD;
          -  have any contraindication to receiving a vaccine.&#xD;
&#xD;
          -  have a Hemoglobin A1c (HbA1c) level &gt;9.0%.&#xD;
&#xD;
          -  be diagnosed with malignancy (subjects without a recurrence in the last 2.5 years will&#xD;
             be allowed) except curatively-treated basal cell carcinoma, melanoma in situ, or&#xD;
             cervical carcinoma.&#xD;
&#xD;
          -  have a condition that projected to limit the life-expectancy to ≤1 year.&#xD;
&#xD;
          -  have autoimmune disease (e.g., rheumatoid arthritis).&#xD;
&#xD;
          -  be using medication(s) known to alter immune response, e.g., high-dose&#xD;
             corticosteroids.&#xD;
&#xD;
          -  have HIV, AIDS, or other immunodeficiency.&#xD;
&#xD;
          -  test positive for hepatitis B virus&#xD;
&#xD;
               -  If the subject tests positive for anti-HBc or anti-HBs, they must be receiving&#xD;
                  treatment for Hepatitis B virus prior to infusion and remain on treatment&#xD;
                  throughout the study.&#xD;
&#xD;
          -  test positive for viremic hepatitis C, HIV1, HIV2, or syphilis.&#xD;
&#xD;
          -  have a resting blood oxygen saturation of &lt;93% (measured by pulse oximetry).&#xD;
&#xD;
          -  be a female who is pregnant, nursing, or of childbearing potential while not&#xD;
             practicing effective contraception.&#xD;
&#xD;
          -  have documented current substance and/or alcohol abuse.&#xD;
&#xD;
          -  have known allergies to latex or eggs.&#xD;
&#xD;
          -  have a known hypersensitivity to dimethyl sulfoxide (DMSO).&#xD;
&#xD;
          -  be an organ transplant recipient (other than corneal, bone, skin, ligament, or tendon&#xD;
             transplant).&#xD;
&#xD;
          -  be actively listed (or expected to be listed) for transplant of any organ (other than&#xD;
             corneal, bone, skin, ligament, or tendon transplant).&#xD;
&#xD;
          -  have any clinically important abnormal screening laboratory values, including but not&#xD;
             limited to:&#xD;
&#xD;
               -  hemoglobin &lt;10.0 g/dL.&#xD;
&#xD;
               -  white blood cell count &lt; 2500/mm3.&#xD;
&#xD;
               -  platelets &lt; 100,000/mm3.&#xD;
&#xD;
               -  prothrombin time/international normalized ratio (PT/INR) ˃ 1.5 not due to a&#xD;
                  reversible cause (i.e. Coumadin).&#xD;
&#xD;
          -  aspartate transaminase, alanine transaminase, or alkaline phosphatase ˃ 2 times upper&#xD;
             limit of normal.&#xD;
&#xD;
          -  have a sitting or resting systolic blood pressure &gt;180 mm Hg or diastolic blood&#xD;
             pressure &gt;110 mm Hg at Screening.&#xD;
&#xD;
          -  have any serious illness or any other condition that, in the opinion of the&#xD;
             investigator, may compromise the safety or compliance of the subject or preclude&#xD;
             successful completion of the study, or that may compromise the validity of the study.&#xD;
&#xD;
          -  be currently participating in an investigational therapeutic or device trial, or have&#xD;
             participated in an investigational therapeutic or device trial within the previous 30&#xD;
             days, or participate in any other clinical trial for the duration of the time that the&#xD;
             subject actively participates in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Research of South Florida</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Physiology Associates</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vista Health Research</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Optimal Research LLC</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>November 3, 2022</last_update_submitted>
  <last_update_submitted_qc>November 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Frailty</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02982915
org study id: 00-0000-03
nct id: NCT02982915
lead sponsor: 
has dmc: Yes
This is a phase I/II, randomized, blinded and placebo-controlled study to test the safety and
      efficacy of Lomecel-B for improving vaccine immune response.
A pilot phase will consist of a 3 subject safety run-in, followed by 20 subject randomized
      phase to evaluate influenza vaccine response at 1 week and 4 weeks post infusion of Lomecel-B
      (Formerly LMSCs). This will be followed by a double-blinded, randomized, placebo-controlled
      phase.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: The incidence of any treatment-emergent serious adverse event (TE-SAE), defined as one or more of the following untoward medical occurrences within 30 days after infusion as assessed by the following:
time frame: 30 days after infusion
description: Is life-threatening (e.g., stroke or non-fatal pulmonary embolism).
Requires inpatient hospitalization or prolongation of existing hospitalization.
Results in persistent or significant disability/incapacity.
Results in death
Results in other clinically significant untoward laboratory test result(s) or medical condition(s), determined per Investigator's judgment.
measure: The ability of Lomecel-B (LMSC) treatment to improve inactivation of influenza virus as assessed by validated hemagglutination inhibition (HAI) assays.
time frame: Baseline Visit, Vaccination Visits, Weeks 1, 2, 4, Month 6 and Month 12 Follow-Up Visits.
description: Measurements of validated hemagglutination inhibition (HAI) assays at follow up visits.
measure: Changes from baseline between the LMSC and placebo cohorts as assessed by plasma cytokine levels:
time frame: Baseline, month 6 and month 12 after infusion
description: Plasma levels of interleukins measured in pg/mL.
measure: Differences in rate of decline from Aging Frailty
time frame: Baseline, month 6 and month 12 after infusion
description: Change in Clinical Frailty rating
measure: Assessed by the Falls Efficacy Scale-International and Performance Oriented Mobility Assessment
time frame: Baseline, month 6 and month 12 after infusion
description: Change in risk of falling
measure: PROMIS Short Form 20a questionnaire
time frame: Baseline, month 6 and month 12 after infusion
description: Change in subject quality of life as assessed by participant-reported outcomes.
measure: PROMIS Mobility questionnaire
time frame: Baseline, month 6 and month 12 after infusion
description: Change in subject quality of life as assessed by participant-reported outcomes.
measure: PROMIS Upper Extremity questionnaire
time frame: Baseline, month 6 and month 12 after infusion
description: Change in subject quality of life as assessed by participant-reported outcomes.
measure: Short Form 36 questionnaire
time frame: Baseline, month 6 and month 12 after infusion
description: Change in subject quality of life as assessed by participant-reported outcomes.
measure: IIEF questionnaire
time frame: Baseline, month 6 and month 12 after infusion
description: Change in subject quality of life as assessed by participant-reported outcomes.
measure: SQOL-F questionnaire
time frame: Baseline, month 6 and month 12 after infusion
description: Change in subject quality of life as assessed by participant-reported outcomes.
measure: Death from any cause
time frame: Within 12 months after infusion
description: Number of participants that die from any cause while enrolled on the trial and after being treated with LMSCs.
measure: Falls Efficacy Scale-International (FES-I)
time frame: Baseline, month 6 and month 12 after infusion
description: Change by participant-reported outcomes. Minimum 16 (no concern about falling) to maximum 64 (severe concern about falling)
measure: Changes from baseline between the LMSC and placebo cohorts as assessed by B & T cell levels:
time frame: Baseline, month 6 and month 12 after infusion
description: Plasma levels of B & T Cells.
measure: Rate of decline in Aging Frailty status as assessed by the 6 minute walk test
time frame: Baseline, month 6 and month 12 after infusion
description: Distance in meters walked in 6 minutes
measure: Rate of decline in Aging Frailty status as assessed by the Short Physical Performance Battery (SPPB)
time frame: Baseline, month 6 and month 12 after infusion
description: Short Physical Performance Battery Assessment
measure: Rate of decline in Aging Frailty status as assessed by the Tinetti POMA Test
time frame: Baseline, month 6 and month 12 after infusion
description: TInetti POMA assessment
measure: Rate of decline in Aging Frailty status as assessed by the Weight Loss
time frame: Baseline, month 6 and month 12 after infusion
description: Weigh measurements at visits
measure: Rate of decline in Aging Frailty status as assessed by the Handgrip Test
time frame: Baseline, month 6 and month 12 after infusion
description: Handgrip strength via dynamometer.
arm group label: Pilot Phase- Cohort A
arm group type: Experimental
description: Single dose of 20 million Longeveron Mesenchymal Stem Cells (LMSCs) will be delivered followed by vaccination with Fluzone High-Dose at 1 week post-infusion.
arm group label: Pilot Phase Cohort B & C
arm group type: Experimental
description: Single dose of 100 million Longeveron Mesenchymal Stem Cells (LMSCs) followed by vaccination with Fluzone High-Dose at either 1 week (Cohort B) or 4 weeks (Cohort C) post infusion.
arm group label: Double-Blind,Randomized,Placebo Phase
arm group type: Experimental
description: 2 cohorts to receive a single infusion of 100 million Longeveron Mesenchymal Stem Cells (LMSCs) (Cohort A: 30 subjects) or placebo (Cohort B:30 subjects) followed by vaccination with Fluzone High-Dose.
intervention type: Biological
intervention name: Longeveron Mesenchymal Stem Cells (LMSCs)
description: Intravenously delivered
arm group label: Double-Blind,Randomized,Placebo Phase
arm group label: Pilot Phase Cohort B & C
arm group label: Pilot Phase- Cohort A
other name: Lomecel-B
intervention type: Biological
intervention name: Fluzone High Dose Vaccine
description: Intramuscular injection
arm group label: Double-Blind,Randomized,Placebo Phase
arm group label: Pilot Phase Cohort B & C
arm group label: Pilot Phase- Cohort A
criteria: 
gender: All
minimum age: 65 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Frailty
sharing ipd: No