Aging Frailty
Conditions
Brief summary
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.
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.
Interventions
Intravenously delivered
BIOLOGICALFluzone High Dose Vaccine
Intramuscular injection
Sponsors
Longeveron Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: | 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. |
| The ability of Lomecel-B (LMSC) treatment to improve inactivation of influenza virus as assessed by validated hemagglutination inhibition (HAI) assays. | Baseline Visit, Vaccination Visits, Weeks 1, 2, 4, Month 6 and Month 12 Follow-Up Visits. | Measurements of validated hemagglutination inhibition (HAI) assays at follow up visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessed by the Falls Efficacy Scale-International and Performance Oriented Mobility Assessment | Baseline, month 6 and month 12 after infusion | Change in risk of falling |
| PROMIS Short Form 20a questionnaire | Baseline, month 6 and month 12 after infusion | Change in subject quality of life as assessed by participant-reported outcomes. |
| PROMIS Mobility questionnaire | Baseline, month 6 and month 12 after infusion | Change in subject quality of life as assessed by participant-reported outcomes. |
| PROMIS Upper Extremity questionnaire | Baseline, month 6 and month 12 after infusion | Change in subject quality of life as assessed by participant-reported outcomes. |
| Short Form 36 questionnaire | Baseline, month 6 and month 12 after infusion | Change in subject quality of life as assessed by participant-reported outcomes. |
| IIEF questionnaire | Baseline, month 6 and month 12 after infusion | Change in subject quality of life as assessed by participant-reported outcomes. |
| SQOL-F questionnaire | Baseline, month 6 and month 12 after infusion | Change in subject quality of life as assessed by participant-reported outcomes. |
| Changes from baseline between the LMSC and placebo cohorts as assessed by plasma cytokine levels: | Baseline, month 6 and month 12 after infusion | Plasma levels of interleukins measured in pg/mL. |
| Falls Efficacy Scale-International (FES-I) | Baseline, month 6 and month 12 after infusion | Change by participant-reported outcomes. Minimum 16 (no concern about falling) to maximum 64 (severe concern about falling) |
| Changes from baseline between the LMSC and placebo cohorts as assessed by B & T cell levels: | Baseline, month 6 and month 12 after infusion | Plasma levels of B & T Cells. |
| Rate of decline in Aging Frailty status as assessed by the 6 minute walk test | Baseline, month 6 and month 12 after infusion | Distance in meters walked in 6 minutes |
| Rate of decline in Aging Frailty status as assessed by the Short Physical Performance Battery (SPPB) | Baseline, month 6 and month 12 after infusion | Short Physical Performance Battery Assessment |
| Rate of decline in Aging Frailty status as assessed by the Tinetti POMA Test | Baseline, month 6 and month 12 after infusion | TInetti POMA assessment |
| Rate of decline in Aging Frailty status as assessed by the Weight Loss | Baseline, month 6 and month 12 after infusion | Weigh measurements at visits |
| Rate of decline in Aging Frailty status as assessed by the Handgrip Test | Baseline, month 6 and month 12 after infusion | Handgrip strength via dynamometer. |
| Death from any cause | Within 12 months after infusion | Number of participants that die from any cause while enrolled on the trial and after being treated with LMSCs. |
| Differences in rate of decline from Aging Frailty | Baseline, month 6 and month 12 after infusion | Change in Clinical Frailty rating |
Countries
United States
Outcome results
None listed