Clinical trial NCT04228666: A Clinical Trial to Determine the Safety and Efficacy of Hope Biosciences Autologous Mesenchymal Stem Cell Therapy (HB-adMSCs) for the Treatment of Alzheimer's Disease
Official title: A Clinical Trial to Determine the Safety and Efficacy of Hope Biosciences Autologous Mesenchymal Stem Cell Therapy (HB-adMSCs) for the Treatment of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Alzheimer Disease
Keywords: Alzheimer's disease
stem cells
adipose derived mesenchymal stem cells
Lead sponsor: Hope Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Hope Biosciences
First posted: 2020-01-14
Enrollment: 0
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Hope Biosciences is conducting a research study of an investigational product called autologous adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as a possible treatment for Alzheimer's disease (AD). The study purpose is to evaluate the safety profile of four IV infusions of HB-adMSCs in subjects with clinical diagnosis of AD.

Detailed description: This is a Phase 1/2a, open-label, non-randomized study in subjects with Alzheimer's disease. 24 patients will be enrolled for the study. The overall objective of this study is to evaluate the safety profile of four IV infusions of autologous adipose-derived mesenchymal stem cells (HB-adMSCs) in subjects with clinical diagnosis of AD. The primary endpoint of this study is to measure the number and frequency of adverse event(s) and/or severe adverse event(s) throughout the study duration. The second endpoint of this study is to evaluate the ability of HB-adMSCs to alter AD-related inflammation via measuring levels of Tumor Necrosis Factor alpha (TNF-a), Interleukin-1 (IL-1), Interleukin-6 (IL-6), C-Reactive Protein (CRP), and markers associated with amyloid deposition, Amyloid beta 40 and Amyloid beta 42. Subjects will also be assessed for cognitive deficits measured by changes from baseline values using Mini Mental Status Examination (MMSE), Alzheimer's disease Cooperative Study Activities of Daily Living (ADCS-ADL), Alzheimer's disease Related Quality of Life (ADRQL), Altoida Neuro Motor Index (NMI) for Digital Biomarkers, and Clinical Dementia Rating Questionnaire (CDR).

Eligibility criteria: Inclusion Criteria:

1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of early stage's (preclinical/mild cognitive impairment) Probable Alzheimer's Disease according to the 2011 NIA-AA criteria.

   * Non-childbearing potential for women is defined as postmenopausal \[last natural menses greater than 24 months; in women under age 55, menopausal status will be documented with serum follicle stimulating hormone (FSH) test\] or undergone a documented bilateral tubal ligation or hysterectomy.
   * Male participants who are sexually active with a woman of childbearing potential must agree to use condoms during the trial unless the woman is using an acceptable means of birth control. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of intrauterine device (IUD), male or female condom and diaphragm.
2. Informed consent signed by the subject
3. Documented Amyloid PET Scan (images and report) positive to amyloid plaques deposits on the brain.
4. If the patient is under any treatment, should have been on a stable dose for at least 30 days prior to signing the informed consent form and there is no intention to modify the dose over the course of the study. (NOTE: Cholinesterase inhibitors (AChEI) (donepezil, galantamine, or rivastigmine) may not be initiated, discontinued or modified after study initiation for the 12-months control period).

Exclusion Criteria:

1. Hospitalization or change of chronic concomitant medication within one month prior to screening.
2. Clinically significant or unstable disease that may interfere with outcome evaluations, including but not limited to:

   * Respiratory Insufficiency
   * Poorly managed hypertension (systolic \>160 mm Hg and/or diastolic \>95 mm Hg) or hypotension (systolic \<90 mm Hg and/or diastolic \<60 mm Hg); or
   * Bradycardia (\<50 beats/min.) or tachycardia (\>100 beats/min.). Otherwise healthy subjects with borderline bradycardia may be discussed with the medical monitor to determine eligibility.
   * Renal insufficiency, defined as eGFR \<40 mL/min based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula, https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr
   * Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within 3 months before screening). If a subject has a history of heart disease of questionable clinical significance, the medical monitor may be contacted to discuss eligibility.
3. Records of PET Scan negative to Amyloid plaques deposition in the brain.
4. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day.
5. Acute intercurrent infections such as Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) or Syphilis.
6. Contraindications for PET scanning, including implanted metallic devices (e.g. non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
7. Is unable or unwilling to comply with protocol follow-up requirements.
8. Enrollment in another investigational study or intake of investigational drug within the previous 30 days.
9. Any condition, which in the opinion of the investigator or the sponsor makes the patient unsuitable for inclusion.

Primary outcomes:
measure: Glucose
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Calcium
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Albumin
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Total Protein
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Sodium
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Total carbon dioxide
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Potassium
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Chloride
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: BUN
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Creatinine
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Alkaline phosphatase
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Alanine aminotransferase
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Aspartate aminotransferase
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Total Bilirubin
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: White blood cell
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Red blood cell
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Hemoglobin
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Hematocrit
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Mean corpuscular volume
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Mean corpuscular hemoglobin
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Mean corpuscular hemoglobin concentration
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Red cell distribution width
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Neutrophils
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Lymphs
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Monocytes
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Eos
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Basophils
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Absolute neutrophils
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Absolute lymphs
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Absolute monocytes
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Absolute Eos
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Absolute Basos
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Immature granulocytes
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Absolute Immature granulocytes
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Platelets
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: Prothrombin time
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
measure: INR
timeFrame: Screening, change from screening at week 0, week 4, week 8, week 13, week 26, week 52.
Secondary outcomes:
measure: Tumor necrosis factor-alpha
timeFrame: week 0, change from baseline at week 13, change from baseline at week 52
measure: Interleukin-1
timeFrame: week 0, change from baseline at week 13, change from baseline at week 52
measure: Interleukin-6
timeFrame: week 0, change from baseline at week 13, change from baseline at week 52
measure: C-reactive protein
timeFrame: week 0, change from baseline at week 13, change from baseline at week 52
measure: Amyloid beta 40
timeFrame: week 0, change from baseline at week 13, change from baseline at week 52
measure: Amyloid beta 42
timeFrame: week 0, change from baseline at week 13, change from baseline at week 52
measure: Volumetric changes in hippocampus, ventriculus, and whole brain
timeFrame: screening, week 26 and 52
measure: Mini Mental Status Exam
timeFrame: week 0, change from baseline at week 4, 10, 13, 19, 26, 33, 40, 46, and 52
measure: Alzheimer's disease Cooperative Study Activities of Daily Living
timeFrame: week 0, change from baseline at week 4, 10, 13, 19, 26, 33, 40, 46, and 52
measure: Quality of Life Enjoyment and Satisfaction Questionnaire
timeFrame: week 0, change from baseline at week 4, 10, 13, 19, 26, 33, 40, 46, and 52
measure: Altoida Neuro Motor Index
timeFrame: week 0, change from baseline at week 4, 10, 13, 19, 26, 33, 40, 46, and 52
measure: Clinical Dementia Rating Questionnaire
timeFrame: week 0, change from baseline at week 4, 10, 13, 19, 26, 33, 40, 46, and 52
Other outcomes:
Locations:
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
Study officials:
affiliation: Clinical Trial Network
name: Djamchid Lotfi, MD
role: PRINCIPAL_INVESTIGATOR
References: