AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery

NCT ID: NCT02065245

Last Updated: 2021-07-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-03

Study Completion Date

2020-10-02

Brief Summary

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The purpose of this study is to look at the safety of treatment with stem cells in patients with Frailty.

Detailed Description

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Conditions

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Frailty

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Pilot phase - Group 1

Group 1 participants will receive Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 20 million allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Pilot Phase - Group 2

Group 2 - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Pilot Phase - Group 3

Group 3 - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Randomized Phase - Group A

Group A - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million allo-hMSCs/kg delivered via peripheral intravenous infusion.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Randomized phase - Group B

Group B - Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 200 million allo-hMSCs/kg delivered via peripheral intravenous infusion.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Randomized Phase - Group C

Group C - Placebo delivered via peripheral intravenous infusion. Participants in this group have the option to receive one additional infusion of 100million allo-hMSCs/kg with a 12 to 18 month interval.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Placebo

Intervention Type BIOLOGICAL

Placebo administered by peripheral intravenous infusion.

Addendum B - Antibiotic free cell Group

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs): 100 million penicillin/streptomycin-free allo-hMSCs/kg delivered via peripheral intravenous infusion. Participants in this group have the option to receive an additional 3 infusions of 100million allo-hMSCs/kg per infusion with a 12 to 18 month interval.

Group Type EXPERIMENTAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Intervention Type BIOLOGICAL

Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion.

Interventions

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Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion

Intervention Type BIOLOGICAL

Placebo

Placebo administered by peripheral intravenous infusion.

Intervention Type BIOLOGICAL

Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs)

Penicillin/Streptomycin-Free Allogeneic Human Mesenchymal Stem Cells (allo-hMSCs) administered by peripheral intravenous infusion.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Provide written informed consent.
* Subjects age greater than or equal to 60 and less than or equal to 95 years at the time of signing the Informed Consent Form.
* Show signs of frailty apart from a concomitant condition as assessed by the Investigator with a frailty score of 4 to 7 using the Clinical Frailty Scale
* Female subjects with an Follicle-stimulating hormone (FSH) equal to or \> 25.8 milli-international units (mIU) /mL (milliliter), if not currently on hormone replacement therapy.

Exclusion Criteria

* Score of less than or equal to 24 on the Mini Mental State Examination (MMSE)
* Inability to perform any of the assessments required for endpoint analysis (report safety or tolerability concerns, perform pulmonary function tests, undergo blood draws, read and respond to questionnaires.
* Active listing (or expected future listing) for transplant of any organ.
* Clinically important abnormal screening laboratory values, including but not limited to: hemoglobin \<8 g/dl, white blood cell count \<3000/mm3, platelets\<80,000/mm3, international normalized ratio (INR) \> 1.5 not due to a reversible cause (i.e. Coumadin), aspartate transaminase, alanine transaminase, or alkaline phosphatase \> 3 times upper limit of normal, total bilirubin \> 1.5 mg/dl.
* Serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. Including, but not limited to: HIV, advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, or cardiac revascularization within the last six months, or severe obstructive ventilatory defect.
* Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.
* Be an organ transplant recipient.
* Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma if recurrence occurs.
* Have a non-pulmonary condition that limits lifespan to \< 1 year.
* Have a history of drug or alcohol abuse within the past 24 months.
* Be serum positive for HIV, hepatitis B Surface Antigen (BsAg) or Viremic hepatitis C.
* Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
* Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion.
* Have hypersensitivity to dimethyl sulfoxide (DMSO)
Minimum Eligible Age

60 Years

Maximum Eligible Age

95 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

Longeveron Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joshua M Hare, MD

Role: PRINCIPAL_INVESTIGATOR

ISCI / University of Miami Miller School of Medicine

Locations

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ISCI/University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status

Countries

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United States

References

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Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, Schulman IH, Longsomboon B, Wolf A, Khan A, Heldman AW, Goldschmidt-Clermont PJ, Hare JM. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.

Reference Type BACKGROUND
PMID: 26933813 (View on PubMed)

Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137.

Reference Type BACKGROUND
PMID: 28977399 (View on PubMed)

Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, Heldman AW, Miki R, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Pujol MV, Da Fonseca M, Oliva AA Jr, Green G, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Goldschmidt-Clermont PJ, Hare JM. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1505-1512. doi: 10.1093/gerona/glx056.

Reference Type BACKGROUND
PMID: 28444181 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://isci.med.miami.edu

Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine

Other Identifiers

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20130646

Identifier Type: -

Identifier Source: org_study_id

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