Lomecel-B on Vaccine-Specific Antibody- Response in Subjects With Aging Frailty (HERA)

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

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.

Study Overview

• Status: Completed
• Conditions: Aging Frailty
• Intervention / Treatment: Biological: Longeveron Mesenchymal Stem Cells (LMSCs); Biological: Fluzone High Dose Vaccine

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 Lomecel-B (Formerly LMSCs). This will be followed by a double-blinded, randomized, placebo-controlled phase.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Fort Myers, Florida, United States, 33912
      • Clinical Physiology Associates
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33176
      • Vista Health Research
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
    • Rockville, Maryland, United States, 20850
      • Optimal Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 63 years to 88 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Longeveron Mesenchymal Stem Cells (LMSCs); Intravenously delivered; Other Names: Lomecel-B; Biological: Fluzone High Dose Vaccine; Intramuscular injection
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.	Biological: Longeveron Mesenchymal Stem Cells (LMSCs); Intravenously delivered; Other Names: Lomecel-B; Biological: Fluzone High Dose Vaccine; Intramuscular injection
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.	Biological: Longeveron Mesenchymal Stem Cells (LMSCs); Intravenously delivered; Other Names: Lomecel-B; Biological: Fluzone High Dose Vaccine; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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:	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.	30 days after infusion
The ability of Lomecel-B (LMSC) treatment to improve inactivation of influenza virus as assessed by validated hemagglutination inhibition (HAI) assays.	Measurements of validated hemagglutination inhibition (HAI) assays at follow up visits.	Baseline Visit, Vaccination Visits, Weeks 1, 2, 4, Month 6 and Month 12 Follow-Up Visits.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline between the LMSC and placebo cohorts as assessed by plasma cytokine levels:	Plasma levels of interleukins measured in pg/mL.	Baseline, month 6 and month 12 after infusion
Differences in rate of decline from Aging Frailty	Change in Clinical Frailty rating	Baseline, month 6 and month 12 after infusion
Assessed by the Falls Efficacy Scale-International and Performance Oriented Mobility Assessment	Change in risk of falling	Baseline, month 6 and month 12 after infusion
PROMIS Short Form 20a questionnaire	Change in subject quality of life as assessed by participant-reported outcomes.	Baseline, month 6 and month 12 after infusion
PROMIS Mobility questionnaire	Change in subject quality of life as assessed by participant-reported outcomes.	Baseline, month 6 and month 12 after infusion
PROMIS Upper Extremity questionnaire	Change in subject quality of life as assessed by participant-reported outcomes.	Baseline, month 6 and month 12 after infusion
Short Form 36 questionnaire	Change in subject quality of life as assessed by participant-reported outcomes.	Baseline, month 6 and month 12 after infusion
IIEF questionnaire	Change in subject quality of life as assessed by participant-reported outcomes.	Baseline, month 6 and month 12 after infusion
SQOL-F questionnaire	Change in subject quality of life as assessed by participant-reported outcomes.	Baseline, month 6 and month 12 after infusion
Death from any cause	Number of participants that die from any cause while enrolled on the trial and after being treated with LMSCs.	Within 12 months after infusion
Falls Efficacy Scale-International (FES-I)	Change by participant-reported outcomes. Minimum 16 (no concern about falling) to maximum 64 (severe concern about falling)	Baseline, month 6 and month 12 after infusion
Changes from baseline between the LMSC and placebo cohorts as assessed by B & T cell levels:	Plasma levels of B & T Cells.	Baseline, month 6 and month 12 after infusion
Rate of decline in Aging Frailty status as assessed by the 6 minute walk test	Distance in meters walked in 6 minutes	Baseline, month 6 and month 12 after infusion
Rate of decline in Aging Frailty status as assessed by the Short Physical Performance Battery (SPPB)	Short Physical Performance Battery Assessment	Baseline, month 6 and month 12 after infusion
Rate of decline in Aging Frailty status as assessed by the Tinetti POMA Test	TInetti POMA assessment	Baseline, month 6 and month 12 after infusion
Rate of decline in Aging Frailty status as assessed by the Weight Loss	Weigh measurements at visits	Baseline, month 6 and month 12 after infusion
Rate of decline in Aging Frailty status as assessed by the Handgrip Test	Handgrip strength via dynamometer.	Baseline, month 6 and month 12 after infusion

Collaborators and Investigators

• Sponsor: Longeveron Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Frailty
• Other Study ID Numbers: 00-0000-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No