Alzheimer's Disease
Conditions
Interventions
Doses of 100-125 x106 NurOwn® (MSC-NTF cells) administered intrathecally at
visits 3, 4 and 5.
Sponsors
Brainstorm Cell Therapeutics, Ltd.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Males and females, ages 50 to 75 years old, inclusive, at the Screening Visit (Visit 1). 2. Clinical diagnosis of prodromal to mild AD at least 6 months prior to enrollment, based on the International Working Group (IWG-2) diagnostic criteria or the National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria. 3. Mini Mental State Examination (MMSE) of 20-30, inclusive, and Clinical dementia rating-global score (CDR-GS) of 0.5 or 1.0 4. Demonstrated abnormal memory function 5. CSF profile consistent with AD: Amyloid Beta 42 (A*42) concentration of 19 pg/ml or ratio of p-tau/Abeta > 0.024 (Elecsys assay) 6. If currently treated with Cholinesterase Inhibitors (AChEI) (donepezil, galantamine, or rivastigmine) or Memantine the dose should be stable for at least 12 weeks prior to Screening (Visit 1). 7. Must have a caregiver that is willing to participate in the study and is able to provide accurate information on the participant's cognitive and functional ability. 8. Must consent to apolipoprotein E (ApoE) genotyping or willing to provide previous test results. 9. If sexually active and of childbearing potential, both females and males must agree to use an effective birth control method during the study and for at least 3 months following the last transplantation, such as: abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or hormonal implant.
Exclusion criteria
Exclusion criteria: 1. Prior stem cell therapy of any kind. 2. Active participation in any other interventional study or use of unapproved AD investigational therapy within 60 days prior to the Screening Visit (Visit 1), unless proven to have been on placebo. 3. Inability to lie flat for the duration of intrathecal cell administration and/or bone marrow aspiration, or inability to tolerate study procedures for any other reason. 4. History of clinically significant autoimmune disease (excluding thyroid disease) that may confound study results, myelodysplastic or myeloproliferative disorder, leukemia or lymphoma, whole body irradiation, hip fracture, or severe scoliosis. 5. Any poorly controlled clinically significant medical condition other than Alzheimer*s disease (e.g., within six months of Screening Visit (Visit 1), such as myocardial infarction, angina pectoris, congestive heart failure, or hypertension (repeated blood pressure >180 mmHg systolic or 100 mmHg diastolic) as well as clinically significant coagulopathy, treatment with anticoagulants that, in the opinion of the investigator, would compromise the safety of participants. 6. Any history of malignancy (e.g., myeloproliferative disorder, leukemia or lymphoma) within the previous 5 years, except for non-melanoma localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of Screening Visit (Visit 1)). 7. Any history of acquired or inherited immune deficiency syndrome. 8. Platelet count, INR, PT or PTT not within the normal range (local protocol) or other risk for increased or uncontrolled bleeding (safety for lumbar puncture and bone marrow). 9. Presence of contraindication to lumbar puncture as judged by local PI, e.g. need for anticoagulant or antiplatelet medications other than aspirin at a dose of * 100 mg/day or clopidogrel. 10. MRI evidence of a) more than three lacunar infarcts, b) territorial infarct or macroscopic hemorrhage, or c) deep white matter lesions (corresponding to a Fazekas score of 3). 11. Pregnant women or women currently breastfeeding. 12. Positive test result for Hepatitis B virus (HBV; surface antigen (HBsAg) and antibodies to core antigen (IgG and IgM anti-HBc)), Hepatitis C virus (HCV), Human Immune deficiency Virus (HIV) 1 and 2. 13. Any medical or neurological/neurodegenerative condition other than AD (e.g.,vascular dementia, dementia with Lewy bodies, and Parkinson*s disease) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns (includes, low vitamin B12 level, low Hb level (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint will be to evaluate the safety and tolerability of 3 intrathecal administrations of NurOwn® (MSC-NTF cells). Safety endpoints include AEs, changes in physical and neurological examination findings, hematology, serum chemistry, urinalysis, vital signs, and requirement of concomitant medications. | — |
Secondary
| Measure | Time frame |
|---|---|
| Modulation of Cerebrospinal Fluid (CSF) and Blood Biomarkers The efficacy of NurOwn® (MSC-NTF cells) will be evaluated by the modulation of CSF and blood biomarkers (neurotrophic factors, neurodegenerative and inflammatory biomarkers) following NurOwn® treatment. CSF and blood samples will be collected as per the schedule of assessments to evaluate biomarkers (NTFs, inflammatory factors, cytokines and miRNAs) in the cerebrospinal fluid (CSF) before each treatment as well as in blood samples (such as Neurofilament Light Chain) throughout the study, to evaluate their relationship to treatment with NurOwn® (MSC-NTF cells). Cognitive Assessments Change from baseline in all cognitive assessments will be summarized. The assessments include Mini Mental State Examination (MMSE), Neuropsychological Test Battery (NTB), Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating * Sum of Boxes (CDR-SB). | — |
Countries
Netherlands
Outcome results
None listed