Allogeneic Human Mesenchymal Stem Cell Infusion Versus Placebo in Patients With Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT02600130
• Recruitment Status: Active, not recruiting
• First Posted: November 9, 2015
• Last Update Posted: November 6, 2019
• Sponsor: Longeveron LLC
• Information provided by (Responsible Party): Longeveron LLC

Tracking Information

• First Submitted Date: November 2, 2015
• First Posted Date: November 9, 2015
• Last Update Posted Date: November 6, 2019
• Actual Study Start Date: October 10, 2016
• Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 6, 2015)

To demonstrate the safety of LMSCs administered to subjects with Alzheimer's disease. [ Time Frame: 30 days post infusion ]

Incidence of any treatment-emergent serious adverse event (TE-SAE), defined as one or more of the following untoward medical occurrences happening within the first 30 days after infusion.

• Life-threatening event (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.
• Leads to other clinically significant untoward laboratory test result(s) or medical condition(s), determined per Investigator's judgement (e.g., new clinically asymptomatic brain microhemorrhages).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 5, 2016)

Preliminary efficacy will be determined by examining for changes in AD status and rate decline as assessed by the following. [ Time Frame: At Baseline, 2, 4, 13, 26, 39, and 52 weeks ]

• Neurological/neurocognitive assessments. ADAS-Cog 11 (Alzheimer's Disease Assessment Scale-cognitive subscale 11) MMSE (Mini Mental State Examination) NPI (Neuropsychiatric Inventory) UPSIT (University of Pennsylvania Smell Identification Test) GDS (Geriatric Depression Scale)
• Quality of life assessments. ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) QOL-AD (Quality of Life-Alzheimer's Disease)
• Blood inflammatory and AD biomarkers. IL-1 IL-6 TGF-β1 TNF-α CRP D-Dimer Fibrinogen ApoE
• Cerebrospinal fluid (CSF) inflammatory biomarkers. IL-1 IL-6 TGF-β1 TNF-α
• CSF biomarkers of AD. Tau. Phosphorylated tau. Beta-amyloid.
• Brain volumetry calculated using MRI, including:

Hippocampal volume. Ventricular volume. Whole-brain volume.

Original Secondary Outcome Measures (submitted: November 6, 2015)

Preliminary efficacy will be determined by examining for changes in AD status and rate decline as assessed by the following. [ Time Frame: At Baseline, 2, 6, 13,26, 39, and 52 weeks ]

• Neurological/neurocognitive assessments. ADAS-Cog 11 (Alzheimer's Disease Assessment Scale-cognitive subscale 11) CBB (CogState Brief Battery; CogState 12-minute battery) MMSE (Mini Mental State Examination) NPI (Neuropsychiatric Inventory) UPSIT (University of Pennsylvania Smell Identification Test) GDS (Geriatric Depression Scale)
• Quality of life assessments. ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) QOL-AD (Quality of Life-Alzheimer's Disease)
• Blood inflammatory and AD biomarkers. IL-1 IL-6 TGF-β1 TNF-α CRP D-Dimer Fibrinogen ApoE CBC with differential PRA
• Cerebrospinal fluid (CSF) inflammatory biomarkers. IL-1 IL-6 TGF-β1 TNF-α
• CSF biomarkers of AD. Tau. Phosphorylated tau. Beta-amyloid.
• Brain volumetry calculated using MRI, including:

Hippocampal volume. Ventricular volume. Whole-brain volume.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Allogeneic Human Mesenchymal Stem Cell Infusion Versus Placebo in Patients With Alzheimer's Disease
• Official Title: A Phase, I Prospective, Randomized, Double-Blinded, Placebo-controlled, Trial to Evaluate the Safety and Potential Efficacy of Longeveron Allogeneic Human Mesenchymal Stem Cell (LMSCs) Infusion Versus Placebo in Patients With Alzheimer's Disease
• Brief Summary: This is a Phase I, prospective, randomized, placebo-controlled, double-blinded study designed to test the safety and efficacy of LMSCs (Longeveron Mesenchymal Stem Cells) for the treatment of subjects with clinically diagnosed Alzheimer's disease.
• Detailed Description: This is a randomized, placebo-controlled clinical trial designed to evaluate the safety and efficacy of LMSCs (Longeveron Mesenchymal Stem Cells) or placebo in subjects with Alzheimer's Disease. Following a successful Safety Run-In Phase, a total of twenty-five (25) subjects will be randomized to (2:2:1) to receive low-dose LMSCs, high-dose LMSCs or placebo. After randomization, baseline imaging, and study product infusion, subjects will be followed up at 2,4,13, 26, 39 and 52 week post study product infusion. Intention-to-treat study population will be used for the purpose of the endpoint analysis and safety evaluations.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Biological: Longeveron Mesenchymal Stem Cells
  via peripheral intravenous infusion
• Biological: Placebo
  via peripheral intravenous infusion

Study Arms

• Experimental: Cohort 1
  Cohort 1 (10 subjects) Target dose 20 million Longeveron Mesenchymal Stem Cells (LMSCs) via peripheral intravenous infusion.
  Intervention: Biological: Longeveron Mesenchymal Stem Cells
• Experimental: Cohort 2
  Cohort 2 (10 subjects) Target dose 100 million Longeveron Mesenchymal Stem Cells (LMSCs)via peripheral intravenous infusion.
  Intervention: Biological: Longeveron Mesenchymal Stem Cells
• Placebo Comparator: Cohort 3
  Cohort 3 (5 subjects) Placebo (Plasmalyte A and 1% human serum albumin (HSA)) via peripheral intravenous infusion.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 5, 2019): 33
• Original Estimated Enrollment (submitted: November 6, 2015): 30
• Estimated Study Completion Date: September 2020
• Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria: All subjects enrolled in this trial must:

• provide written informed consent;
• be 50 - 80 years of age at the time of signing the Informed Consent form;
• have a body mass of 45 - 150 kg;
• at the time of enrollment, be diagnosed with AD in accordance with the NINCDS-AA criteria;
• score between 18 and 24 on the Mini Mental State Examination (MMSE);
• has one (or more) identified adult caregiver who is willing to provide written informed consent for his/her own participation; is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥2 hours/day ≥3 days/week; and agrees to accompany the subject to each study visit;
• blood oxygen saturation ≥93% determined via pulse oximetry;
• have a brain MRI consistent with AD;
• have a PET scan using an FDA-approved tracer (e.g., AMYViD, Vizamyl, or Neuraceq), and which indicates the presence of beta-amyloid plaques in the cerebral cortex, within 5 years of enrollment;
• have normal levels of thyroid hormone (free T4) and thyroid-stimulating hormone (TSH);
• have normal levels of B12 and folate;
• have a designated study partner who will accompany the subject to all clinic visits and participate in the subject's clinical assessments; or
• be living in the community, including in an assisted living facility, but excluding long-term care nursing facilities.

Exclusion Criteria: All subjects enrolled in this trial must not:

• be unable to perform any of the assessments required for endpoint analysis;
• show signs of dementia other than AD, such as from AIDS (Acquired Immunodeficiency Syndrome), CJD (Creutzfeldt-Jakob disease), LBD (Lewy Bodies dementia), CVD (Cerebrovascular dementia), PSP (Progressive Supranuclear Palsy), MCI (multiple cerebral infarctions) or NPH (normal pressure hydrocephalus);
• have any other neurodegenerative disease;
• have a history of a seizure disorder;
• have clinically important abnormal screening laboratory values beyond AD;
• have any conditions that would contraindicate an MRI, such as the presence metallic objects in the eyes, skin, or heart;
• have any conditions that would contraindicate a PET scan;
• have > 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite"), a single area of superficial siderosis, or evidence of a prior macrohemorrhage as assessed by MRI;
• be currently using corticosteroids or similar powerful steroidal anti-inflammatory medication (e.g., Prednisone) on a regular basis (exceptions allowed include regular use of steroidal nasal sprays, topical steroids, and estrogen-replacement therapy);
• be active listed (or expected to be listed) for transplant of any organ;
• be an organ transplant recipient;
• have a known hypersensitivity to dimethyl sulfoxide (DMSO).
• have a condition that is projected to limited life expectancy to < 1 year.
• have a sitting or resting systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg at Screening;
• have a history of alcohol or drug abuse within the past 5 years.
• have been diagnosed with malignancy within the past 5 years, with the exception of curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma;
• be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraception (female subjects must undergo a urine pregnancy test at screening and on the infusion day prior to infusion);
• 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;
• have any serious illness or any other condition that, in the opinion of the investigator, may compromise the validity of the study (e.g., signs of stroke, traumatic brain injury (TBI), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Parkinsonism;
• have participated in any investigational therapeutic or device trial within the past 5 years that the investigator feels would influence or affect the outcome of the study;
• be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial;
• be positive for HIV, Syphilis and Hepatitis C; or
• be positive for Hepatitis B. If the subject tests positive for anti-HBc or anti-HBs, subject must be currently receiving treatment for hHepatitis B prior to infusion and remain on treatment throughout the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02600130
• Other Study ID Numbers: 00-0000-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Longeveron LLC
• Study Sponsor: Longeveron LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Longeveron LLC
• Verification Date: November 2019