The primary objective is to determine the safety, tolerability and preliminary efficacy of repeated intrathecal administration of NurOwn® (MSC-NTF: Autologous Mesenchymal Stem Cells [MSC] Secreting Neurotrophic Factors [NTF]) given three times at…
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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).
Background summary
This is an open-label study with a single treatment arm involving 40
participants with Alzheimer*s Disease at multiple investigational study sites.
After providing informed consent, participants meeting the inclusion and
exclusion criteria will be enrolled and 1-4 weeks later will undergo a bone
marrow aspiration (BMA). The first intrathecal (IT) administration will be at
Visit 3 (Week 0), 6-10 weeks after screening/enrollment visit, with the
subsequent treatments at Visit 4 (Week 8) and Visit 5 (Week 16). Following the
third and last treatment, participants will be followed through a 12 week post
treatment Visit 6 (Week 28) and a final follow-up to assess safety and disease
progression at Visit 7 (Week 42).
Each subject*s participation in the study will last for approximately 52 weeks
(12 months), consisting of:
* An approximate 10-week pretreatment period during which participants will
undergo bone marrow aspiration and baseline evaluations
* A 16-week treatment period during which participants will be administered 3
treatments of NurOwn® (MSC-NTF cells) at 8-week intervals (Day 0-1, week 8, and
week 16)
* A 12-week follow-up period (Week 28, Visit 6)
* A 14-week follow-up period to assess safety and clinical disease progression
(Week 42, Visit 7)
Study drug will be supplied in one 5 mL syringe containing 4 mL of NurOwn®
(MSC-NTF cells) suspension at a dose of 100-125 x106 cells for IT
administration.
Study objective
The primary objective is to determine the safety, tolerability and preliminary
efficacy of repeated intrathecal administration of NurOwn® (MSC-NTF: Autologous
Mesenchymal Stem Cells [MSC] Secreting Neurotrophic Factors [NTF]) given three
times at two monthly intervals to participants with prodromal to mild
Alzheimer*s Disease.
The secondary objective is to evaluate the effect of NurOwn upon blood and CSF
biomarkers and cognitive and clinical outcome measures, including Mini Mental
State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT),
Clinical Dementia Rating Scale * Sum of Boxes (CDR-SB), Neuropsychological Test
Battery (NTB) subtests, Delis-Kaplan Executive Function System (D-KEFS),
Category Fluency and Letter Fluency tests and Amsterdam Instructional
Activities of Daily Living * Short Version (A-IADL-Q-SV), to measure safety and
efficacy.
Study design
This is an open-label study with a single treatment arm involving 40
participants with Alzheimer*s Disease at multiple investigational study sites.
After providing informed consent, participants meeting the inclusion and
exclusion criteria will be enrolled and 1-4 weeks later will undergo a bone
marrow aspiration (BMA). The first intrathecal (IT) administration will be at
Visit 3 (Week 0), 6-10 weeks after screening/enrollment visit, with the
subsequent treatments at Visit 4 (Week 8) and Visit 5 (Week 16). Following the
third and last treatment, participants will be followed through a 12 week post
treatment Visit 6 (Week 28) and a final follow-up to assess safety and disease
progression at Visit 7 (Week 42).
Intervention
Doses of 100-125 x106 NurOwn® (MSC-NTF cells) administered intrathecally at
visits 3, 4 and 5.
Study burden and risks
The study drug may have side effects. These side effects are common (occurs in
1 in 10 people or more):
* Headache
* Back pain
* Fever
* Pain in joint
* Injection Site Pain
* Constipation
* Pain in Extremity
* Neck Pain
* Nausea
* Cough
* Muscle pain
Risks to an Embryo or Fetus, or to a Breastfeeding Infant
There may be unforeseen risks to an unborn child or breastfeeding infant
associated with taking NurOwn® (MSC-NTF cells). The effect of MSC-NTF cells on
an embryo or fetus, or on a breastfeeding infant, is unknown and may be
harmful. Because of these unknown risks, women cannot take part in this study
if they are:
* Pregnant
* Trying to become pregnant
* Breastfeeding
Risk of Bone Marrow Aspiration
The most common and expected side-effects and discomforts reported when
undergoing a bone marrow aspiration include the following:
* redness of the skin (erythema)
* swelling of the skin (induration)
* tenderness or pain at the site
* itching at the site
* infection
* fever
* damage to bone, nerve or muscle in hip region
Risks of Intrathecal Injection by Lumbar Puncture
A lumbar puncture is a routine procedure that will be used to administer the
study drug and to collect CSF from the fluid filled space below the end of the
spinal cord.
When spinal fluid is removed during a lumbar puncture, the risks include
headache, bleeding and pain at the site where the needle was put in, and
infection. Pain during the lumbar puncture procedure will be prevented or
minimized by using local anesthesia (lidocaine). Infection after a lumbar
puncture is very rare, but serious, and would be treated with antibiotics.
Headache can occur if the lining around the spinal fluid (dura) is torn and
some of the fluid leaks out. Post-lumbar puncture headaches are more common in
females and in people less than 30 years old. This headache can be mild to
severe. The patient may also have nausea, dizziness and ringing in the ears.
Post-lumbar puncture headaches get worse when sitting or standing.
Occasionally, the headache may be severe enough to interfere with normal daily
activities.
Risks of Magnetic Resonance Imaging (MRI):
You will also have a Magnetic Resonance Imaging (MRI) brain scan at the
beginning of the study to look at the changes in your brain which occur as a
result of AD and which are thought to lead to the symptoms you may have.
For the MRI scan you would need to lie down and keep still in the scanner for
approximately 30 minutes. At one point in the procedure you would be given an
injection with a solution called gadolinium so that the scanner can detect
particular changes in the brain. This solution is routinely used in MRIs. In
addition, if you are a woman who can have children, a pregnancy test from a
urine sample would be performed before each MRI scan to be sure you are not
pregnant.
Risks of Cognitive Scales (MMSE, FCSRT, D-KES and NTB) and Questionnaires
(A-ADL-Q-SV and CDR):
All of the assessments are widely accepted ways of assessing the status of
patients with AD. Completing the cognitive scales/questionnaires may make the
patient/caregiver feel uncomfortable, including emotional or mental discomfort.
The patient/caregiver may refuse to answer any of the questions and may take a
break at any time during the study.
Risks of Possible X-Ray-Guided Lumbar Puncture Procedure
If the doctor performing the administration of study drug is not able to safely
access the spinal fluid, he or she may choose to have the procedure performed
with the assistance of X-ray guidance.
If the doctor chooses to perform the procedure under X-ray guidance, the
patient will be exposed to radiation.
The total amount of radiation exposure is equal to a whole-body exposure of
about 2.9 milliSieverts (mSv).
A possible effect that could occur at doses used in this study is a slight
increase in the risk of developing cancer later in life.
HIV Testing
As a part of this study, a sample of blood is being tested for the presence of
HIV. If the blood test results are positive, the results of that test, and
demographic information about the patient will be reported to the Department of
Health as is required by law. In addition, this information will be available
on the hospital*s laboratory reporting system.
Unknown Risks
There may be risks or side effects related to the study drug/device that are
unknown at this time. The patient will be notified of any significant new
findings that become known that may affect their willingness to continue in the
study.
Bazel St., POB 2650 12
Kiryat Aryeh, Petach Tikva 4912502
IL
Bazel St., POB 2650 12
Kiryat Aryeh, Petach Tikva 4912502
IL
Listed location countries
Age
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
<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.
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 (<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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-002872-11-NL |
| CCMO | NL74415.000.20 |