Clinical trial NCT02982915: Lomecel-B on Vaccine-Specific Antibody- Response in Subjects With Aging Frailty
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Aging Frailty
Lead sponsor: Longeveron Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-06
Enrollment: 62
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
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:
timeFrame: 30 days after infusion
measure: The ability of Lomecel-B (LMSC) treatment to improve inactivation of influenza virus as assessed by validated hemagglutination inhibition (HAI) assays.
timeFrame: Baseline Visit, Vaccination Visits, Weeks 1, 2, 4, Month 6 and Month 12 Follow-Up Visits.
Secondary outcomes:
measure: Changes from baseline between the LMSC and placebo cohorts as assessed by plasma cytokine levels:
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Differences in rate of decline from Aging Frailty
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Assessed by the Falls Efficacy Scale-International and Performance Oriented Mobility Assessment
timeFrame: Baseline, month 6 and month 12 after infusion
measure: PROMIS Short Form 20a questionnaire
timeFrame: Baseline, month 6 and month 12 after infusion
measure: PROMIS Mobility questionnaire
timeFrame: Baseline, month 6 and month 12 after infusion
measure: PROMIS Upper Extremity questionnaire
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Short Form 36 questionnaire
timeFrame: Baseline, month 6 and month 12 after infusion
measure: IIEF questionnaire
timeFrame: Baseline, month 6 and month 12 after infusion
measure: SQOL-F questionnaire
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Death from any cause
timeFrame: Within 12 months after infusion
measure: Falls Efficacy Scale-International (FES-I)
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Changes from baseline between the LMSC and placebo cohorts as assessed by B & T cell levels:
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Rate of decline in Aging Frailty status as assessed by the 6 minute walk test
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Rate of decline in Aging Frailty status as assessed by the Short Physical Performance Battery (SPPB)
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Rate of decline in Aging Frailty status as assessed by the Tinetti POMA Test
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Rate of decline in Aging Frailty status as assessed by the Weight Loss
timeFrame: Baseline, month 6 and month 12 after infusion
measure: Rate of decline in Aging Frailty status as assessed by the Handgrip Test
timeFrame: Baseline, month 6 and month 12 after infusion
Other outcomes:
Locations:
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Vista Health Research
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Rockville
country: United States
facility: Optimal Research LLC
state: Maryland
Study officials:
References: