A Phase 2a, Open-label, Multicenter Study to Evaluate Biomarkers and Safety of Repeated Administration of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors; MSC-NTF cells) in Participants with Prodromal to Mild Alzheimer*s Disease
- Conditions
- AlzheimerAlzheimer's Disease10012272
- Registration Number
- NL-OMON50920
- Lead Sponsor
- Worldwide Clinical Trials Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 20
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 (Aβ42) concentration of
<1000 pg/ml AND P-tau >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.
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 and Syphilis (Treponema
Pallidum).
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 (<100); hypothyroid disease).
14. History within the past 6 months or evidence of clinically significant
psychiatric illness (e.g. major depression, suicidality, schizophrenia, or
bipolar affective disorder).
15. Any condition, which in the opinion of the investigator or the Sponsor
makes the patient unsuitable for inclusion.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• To evaluate AD-specific, neuroinflammatory, neurotrophic and<br /><br>neurodegenerative biomarkers and safety of 3 intrathecal (IT) administrations<br /><br>of NurOwn® (MSC-NTF cells) given at two monthly intervals to participants with<br /><br>prodromal to mild Alzheimer*s Disease.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• To evaluate cognitive and clinical efficacy outcome measures, including<br /><br>CDR-SB, FCSRT, NTB and D-KEFS subtests, A-IADL-Q-SV, as well as the MMSE.</p><br>