Alzheimer's Disease Stem Cells Multiple Infusions

Study Overview
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Brief Summary
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The purpose of this research study is to test the safety, possible side effects, and possible effectiveness of mesenchymal stem cell infusions when given to people with a diagnosis of mild to moderate Alzheimer's disease.

Official Title
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A Phase I, Prospective, Open-label Trial to Evaluate the Safety, Tolerability and Exploratory Outcomes of Multiple Allogeneic Human Mesenchymal Stem Cells (HMSC) Infusions in Patients With Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: Approximately 100 million cells allogeneic hMSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects enrolled in this trial must: Provide written informed consent Male or female subjects aged 50-85 years at time of signing Informed Consent Mini-Mental State Examination (MMSE) between 20-26 Amyloid PET scan or CSF Aß1-42 positive for the presence of amyloid Meet criteria for either Alzheimer's Disease or probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINDCDS/ARDRA) Subjects, if taking cholinesterase inhibitor medications (donepezil, rivastigmine (oral or transdermal) or galantamine), are required to have been taking them on a stable dose for at least 3 months prior to Baseline Visit These medicines are not required Subjects already taking memantine will not have an effect in the inclusion/exclusion criteria. Have a study partner No clinically significant abnormal screening laboratory values, as determined by the investigator Women must be postmenopausal, surgically sterile, or having infertility. A postmenopausal woman is defined as either having an intact uterus with at least 12 months of spontaneous amenorrhea or a diagnosis of menopause, defined as an Follicular Stimulating Hormone (FSH) level of > 25 IU/L Exclusion Criteria: All subjects enrolled must not have: Dementia other than AD A negative Amyloid PET scan Other neurodegenerative disease Significant psychiatric illness (e.g., uncontrolled major depression, schizophrenia, bipolar affective disorder) History of seizures Contraindication for Magnetic Resonance Imaging (MRI) History of malignancy, except: > 5 years in remission prior to screening Be excised or treated basal cell, squamous carcinoma or melanoma in situ Prostate cancer in situ Cervical carcinoma in situ Uncontrolled medical conditions Hypertension Diabetes Unstable angina or history of Myocardial Infarction (MI) within 1 year prior to screening History of alcohol or drug use disorder (except tobacco use disorder) within 2 years before the screening visit Brain MRI at screening that shows evidence of findings incompatible with a diagnosis of Alzheimer's disease. Volumetric MRI scans done within 6 months prior to ICF signature will be accepted if completed locally. History of bleeding disorder History of or positive results for Human Immunodeficiency Virus (HIV) History of or positive results for Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) Hypersensitivity to dimethyl sulfoxide (DMSO) Inability to perform any of the assessments required for endpoint analysis Currently receiving (or received within four weeks of screening) experimental agents for the treatment of AD or enrolled in clinical trials in the prior 3 months Be a transplant recipient, or on active listing (or expected future listing) for transplant of any organ. 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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hMSC Treatment group<br>Participants in the hMSC treatment group will receive a total of 4 doses of the hMSC intervention. Each dose will be administered once about every 13 weeks within a year period. | Biological: Approximately 100 million cells allogeneic hMSC<br>* Umbilical cord-derived, allogeneic hMSC administered intravenously at a dose of approximately 100 million cells per infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Incidence of any Treatment-Emergent Serious Adverse Events (TE-SAEs) | All adverse events will be evaluated by the investigator for relationship with the study intervention. Treatment-Emergent Serious Adverse Events is defined as any untoward medical occurrence with a reasonable possibility that it is caused by the study intervention that: Is life-threatening (e.g.; leads to stroke or non-fatal pulmonary embolism); Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity Results in other clinically significant sign(s) or symptom(s), (e.g.; clinically asymptomatic brain microhemorrhages); or Results in death | One month post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive function over time as assessed by the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog 11) | The ADAS-Cog 11 is a 13-item version of ADAS-Cog comprising of the original 11-item ADAS-Cog as well as Delayed Recall and Digit Cancellation items. The total score ranges from 0-85 points, with a lower score indicating better performance. | Up to Week 65 | 
| Cognitive function over time as assessed by the Mini Mental State Examination (MMSE) of Folstein test | The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The total score ranges from 0-30, with a higher score indicating better cognitive performance. | Up to Week 65 | 
| Depressive symptoms over time as assessed by the Geriatric Depression Scale (GDS) Short Version | The GDS is a 15-item questionnaire with each item counting as one point. The total score ranges from 0 to 15 with a score greater than 5 indicating possible depression. | Up to Week 65 | 
| Participant quality of life over time assessed via Alzheimer's Disease Related Quality of Life (ADRQL-40) Questionnaire as completed by the caregiver | ADRQL-40 is a questionnaire completed by the caregiver assessing the quality of life of the participant with AD. The total score for the ADRQL is computed by summing the values assigned to the responses, dividing the sum by the maximum value for the scale and multiplying the results by 100 to obtain a percentage score of 0 to 100. A higher score reflects a higher quality of life. | Up to Week 65 | 
| Participant quality of life over time as assessed via the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Questionnaire as completed by the caregiver | The ADCS-ADL is a 23 item questionnaire completed by the caregiver assessing the basic and instrumental activities of daily living by the AD participant. Total score range from 0-78 with the higher score indicating increased independence. | Up to Week 65 | 
| Neuropsychiatric Inventory-Q (NPI-Q) Scores over time | The NPI-Q is a questionnaire used to assess behavioral changes common in dementia patients. This questionnaire is completed by the caregiver. The questionnaire consists of 12 items with each item having a scoring range between 0-3. The higher score indicates a more severe neuropsychiatric symptomatology. | Up to Week 52 | 
| Caregiver's Quality of life over time as assessed by the Caregiver Self-Assessment Questionnaire scores | The Caregiver Self-Assessment questionnaire is completed by the caregiver. It is an 18-item questionnaire answered with a yes or no. Evidence of distress is indicated for having over 10 yes answers. | Up to Week 52 | 
| Biomarker levels over time | Serum blood inflammatory and biomarker levels will be evaluated including Interleukin-6 (IL-6), Neurofilament light (NfL), Amyloid Beta 40 (Aβ40) and Amyloid Beta 42 (Aβ42) in pg/mL. | Up to Week 65 | 
| Serum ApoE level over time | Serum blood Apolipoprotein E (ApoE) will be evaluated in mg/dL. | Up to Week 65 | 
| Serum PRA level over time | Serum blood Plasma Renin Activity (PRA) will be evaluated in ng/mL per hour. | Up to Week 65 | 
| Serum Tau protein level over time | Serum blood Tau protein level will be evaluated in ng/L. | Up to Week 65 | 
| Cerebrospinal Fluid (CSF) Biomarker levels over time | CSF inflammatory and biomarker levels will be evaluated including Interleukin-6 (IL-6), Neurofilament light (NfL), Amyloid Beta 40 (Aβ40) and Amyloid Beta 42 (Aβ42) in pg/mL. | Up to Week 52 | 
| CSF ApoE level over time | CSF Apolipoprotein E (ApoE) levels will be evaluated in mg/dL. | Up to Week 52 | 
| CSF PRA level over time | CSF Plasma Renin Activity (PRA) levels will be evaluated in ng/mL per hour. | Up to Week 52 | 
| CSF Tau protein level over time | CSF Tau protein levels will be evaluated in ng/L. | Up to Week 52 | 
| Change in hippocampal volume | Change in hippocampal volume will be assessed via MRI Brain volumetric studies | Baseline to Week 6, Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Stem cells, Alzheimer's Disease