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Human Mesenchymal Stem Cells (LMSCs) on Vaccine-Specific Antibody- Response in Subjects With Aging Frailty (HERA)

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ClinicalTrials.gov Identifier: NCT02982915
Recruitment Status : Recruiting
First Posted : December 6, 2016
Last Update Posted : March 13, 2020
Sponsor:
Information provided by (Responsible Party):
Longeveron LLC

Tracking Information
First Submitted Date  ICMJE November 17, 2016
First Posted Date  ICMJE December 6, 2016
Last Update Posted Date March 13, 2020
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2019)
  • 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 ]
    • 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.
  • Prevention of the illness caused by any influenza viral type/subtype in association with influenza like symptoms: [ Time Frame: Within 7 months after vaccination ]
    Number of participants with sore throat, cough, sputum production, wheezing or difficulty breathing concurrent with fever, chills, tiredness, headaches and myalgia.
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
  • 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 ]
    • 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.
  • Changes from baseline through month 12 in adaptive immunity and primary B cell response to the influenza vaccine in subjects with Aging Frailty. [ Time Frame: Week 1 and Week 4 post vaccination, month 6 and month 12 post infusion follow up ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
  • Changes from baseline between the LMSC and placebo cohorts as assessed by plasma cytokine levels: [ Time Frame: Month 6 and month 12 after infusion ]
    Plasma levels of interleukins measured in pg/mL.
  • Differences in rate of decline from Aging Frailty [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in Clinical Frailty rating
  • Assessed by the Falls Efficacy Scale-International and Performance Oriented Mobility Assessment [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in risk of falling
  • PROMIS Short Form 20a questionnaire [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in subject quality of life as assessed by participant-reported outcomes.
  • PROMIS Mobility questionnaire [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in subject quality of life as assessed by participant-reported outcomes.
  • PROMIS Upper Extremity questionnaire [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in subject quality of life as assessed by participant-reported outcomes.
  • Short Form 36 questionnaire [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in subject quality of life as assessed by participant-reported outcomes.
  • IIEF questionnaire [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in subject quality of life as assessed by participant-reported outcomes.
  • SQOL-F questionnaire [ Time Frame: Baseline, month 6 and month 12 after infusion ]
    Change in subject quality of life as assessed by participant-reported outcomes.
  • Death from any cause [ Time Frame: Within 12 months after infusion ]
    Number of participants that die from any cause while enrolled on the trial and after being treated with LMSCs.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2016)
  • Post-vaccination changes from baseline in the influenza specific plasmablast differential between the LMSC and Placebo Cohorts [ Time Frame: At 1 week and 4 weeks post vaccination ]
    • Prevention of the illness caused by any influenza viral type/subtype in association with influenza like symptoms (e.g., sore throat, cough, sputum production, wheezing or difficulty breathing concurrent with fever, chills,tiredness, headaches and myalgia).
  • Changes from baseline between the LMSC and Placebo Cohorts as assessed by biomarkers [ Time Frame: Month 6 and month 12 post infusion ]
  • Differences in rate of decline from Aging Frailty [ Time Frame: Baseline, Month 6 and month 12 post infusion ]
  • Changes in subject quality of life (QOL) [ Time Frame: Baseline, Month 6 and month 12 post infusion ]
  • Death from any cause [ Time Frame: Month 6 and month 12 post infusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Human Mesenchymal Stem Cells (LMSCs) on Vaccine-Specific Antibody- Response in Subjects With Aging Frailty
Official Title  ICMJE Effects of Intravenous Delivery of Longeveron Human Mesenchymal Stem Cells (LMSCs) on Vaccine-Specific Antibody Responses in Subjects With Aging Frailty
Brief Summary This is a phase I/II, randomized, blinded and placebo-controlled study to test the safety and efficacy of LMCSs for improving vaccine immune response.
Detailed Description 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 LMSCs. This will be followed by a double-blinded, randomized, placebo-controlled phase.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Aging Frailty
Intervention  ICMJE
  • Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
    Intravenously delivered
  • Biological: Fluzone High Dose Vaccine
    Intramuscular injection
Study Arms  ICMJE
  • Experimental: Pilot Phase- Cohort A
    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.
    Interventions:
    • Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
    • Biological: Fluzone High Dose Vaccine
  • Experimental: Pilot Phase Cohort B & C
    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.
    Interventions:
    • Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
    • Biological: Fluzone High Dose Vaccine
  • Experimental: Double-Blind,Randomized,Placebo Phase
    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.
    Interventions:
    • Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
    • Biological: Fluzone High Dose Vaccine
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: December 6, 2018)
83
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2016)
43
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • be willing and able to provide written informed consent and comply with all procedures required by the protocol.
  • be 65 - 90 years of age at the time of signing the Informed Consent Form.
  • have a diagnosis of Aging Frailty, with a score of 4 to 7 using the Canadian Frailty Scale.
  • have a six-minute walk test (6MWT) distance of 200m - 400m for each of 2 trials, and the 2 trials must be within 15% of each other.
  • have total bilirubin between 0.3 - 1.9 mg/dL.

Exclusion Criteria:

  • be unwilling or unable to perform any of the assessments required by the Protocol.
  • score ≤24 on the Mini Mental State Examination (MMSE).
  • have previously received current year's flu-vaccine.
  • have any contraindication to receiving a vaccine.
  • have a Hemoglobin A1c (HbA1c) level >9.0%.
  • be diagnosed with malignancy (subjects without a recurrence in the last 2.5 years will be allowed) except curatively-treated basal cell carcinoma, melanoma in situ, or cervical carcinoma.
  • have a condition that projected to limit the life-expectancy to ≤1 year.
  • have autoimmune disease (e.g., rheumatoid arthritis).
  • be using medication(s) known to alter immune response, e.g., high-dose corticosteroids.
  • have HIV, AIDS, or other immunodeficiency.
  • test positive for hepatitis B virus

    • If the subject tests positive for anti-HBc or anti-HBs, they must be receiving treatment for Hepatitis B virus prior to infusion and remain on treatment throughout the study.
  • test positive for viremic hepatitis C, HIV1, HIV2, or syphilis.
  • have a resting blood oxygen saturation of <93% (measured by pulse oximetry).
  • be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraception.
  • have documented current substance and/or alcohol abuse.
  • have known allergies to latex or eggs.
  • have a known hypersensitivity to dimethyl sulfoxide (DMSO).
  • be an organ transplant recipient (other than corneal, bone, skin, ligament, or tendon transplant).
  • be actively listed (or expected to be listed) for transplant of any organ (other than corneal, bone, skin, ligament, or tendon transplant).
  • have any clinically important abnormal screening laboratory values, including but not limited to:

    • hemoglobin <10.0 g/dL.
    • white blood cell count < 2500/mm3.
    • platelets < 100,000/mm3.
    • prothrombin time/international normalized ratio (PT/INR) ˃ 1.5 not due to a reversible cause (i.e. Coumadin).
  • aspartate transaminase, alanine transaminase, or alkaline phosphatase ˃ 2 times upper limit of normal.
  • have a sitting or resting systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg at Screening.
  • have any serious illness or any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study, or that may compromise the validity of the study.
  • be 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years to 90 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anthony Oliva, PhD (305) 909-0840 aoliva@longeveron.com
Contact: Geoff Green (305) 909-0840 ggreen@longeveron.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02982915
Other Study ID Numbers  ICMJE 00-0000-03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Longeveron LLC
Study Sponsor  ICMJE Longeveron LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Longeveron LLC
Verification Date March 2020

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