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Cell Therapy Institute S.A., Appendix 3 to the Agreement
PATIENT INFORMATION
The patient has been qualified for a Therapy consisting in experimental individual
treatment, a medical therapeutic experiment administered to patients suffering
from the Amyotrophic Lateral Sclerosis (ALS).
This document contains key information about the proposed Therapy. The
Institute expects the Patient to read it and understand the aim of the Therapy
before making the decision.
Below is the key information about this medical treatment experiment. Any other
questions and doubts will be explained to you by the Institute Medical Team.
What is the aim of the Therapy?
The aim of the medical treatment experiment is to help ALS patients by using a
medicinal product of advanced treatment based on allogenic mesenchymal base
cells isolated from Wharton’s jelly in the umbilical cord (further referred to as the
Product). A clinical aim here is to develop a treatment method able to slow down
the pace of disease development.
Research done in the recent decade or so has already confirmed the effects and
safety of using mesenchymal base cells collected from bone marrow in, e.g.,
treatment of difficult leukaemia cases, complications after hematopoietic cell
transplant, and of other disorders, such as: treatment of wounds, burns,
damaged joints, and rather frequent applications in aesthetic medicine.
Supporting the ALS treatment is one more possible application. The stem cells
can be isolated from the patient’s own body (bone marrow, adipose tissue) or
from a third party donor. In the planned experiment, the cells will be collected
from what is known as Wharton’s jelly. It is a jelly-like substance present in the
umbilical cord and containing a great number of mesenchymal stem cells. There
is increasingly abundant evidence that these cells can support the survival of
motor neuron during ALS development. They are very well tolerated by the
recipient’s immune system. A careful analysis of results obtained from clinical
studies done so far on a sample of more than 1,000 patients has proven that the
application of mesenchymal cells in treatment of many diseases is safe.
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Cell Therapy Institute S.A., Appendix 3 to the Agreement
Should the Patient participate in the Therapy?
Our objective is to assess how much the application of mesenchymal stem cells
can slow down the progress of the disease. The decision to participate in the
Therapy belongs to the Patient. The role of the medical team of the Institute
consists in presenting the Therapy guidelines and discussing this document with
the Patient and—if the Patient decides to take part in the Therapy—also in
helping him/her to fill out the Informed Consent Form (Appendix 1a to the
Agreement).
Can the Patient quit the Therapy after making decision to take part in it?
Participation in the Therapy is absolutely voluntary. The Patient is free to quit the
Therapy at any phase of the process. The Institute guarantees that resignation
from continuing the Therapy will in no way affect the access to further treatment
and its quality in a clinic chosen by the Patient. The decision to quit the
experiment should be well contemplated in advance.
What procedures are included in the Therapy?
The Therapy consists of 3 administrations of the Product into the subarachnoid
space in the lumbar section of the spinal canal by performing a lumbar puncture,
repeated every two months. By permission of the Main Pharmaceutical
Inspectorate and the National Centre of Tissue and Cell Banking, the Cell
Engineering Laboratory at PBKM will prepare mesenchymal cells isolated from
Wharton’s jelly in the umbilical cords of healthy third party donors, following a
prior medical interview, tests of the blood of the donor's mother, and following
the mother’s written consent to take a cord tissue sample.
A Patient qualified for the experiment will get a routine health check-up of heart
rate, arterial blood pressure, body temperature, body weight, and a blood
sample will be taken for routine lab tests and for the purpose of measuring its
immunological and genetic properties. The peripheral blood and the cerebrospinal fluid will be sampled before each Product administration.
Details of the Therapy and follow up.
The Product is administered in an operating room. The Institute’s doctor, his
hands surgically disinfected, dressed in a sterile surgeon’s gown, wearing a
mask, and sterile gloves, being assisted by a nurse unwraps a sterile kit which
contains a tool for washing the operative field, sterile washing swabs, two 2 ml
hypodermic syringes, a 5 ml hypodermic syringe (1 piece to sample the cerebro-
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Cell Therapy Institute S.A., Appendix 3 to the Agreement
spinal fluid for lab testing), a 10 ml hypodermic syringe (1 piece), a sterile
container for the cerebro-spinal fluid, a disposable sterile surgical draping, a
sterile dressing, two syringe needles Imr 7 (2 pieces for topical anaesthesia and
for drawing the Product into the syringe) a No. 12 needle for drawing the local
anaesthetic, and a No. 11-12 needle for the lumbar puncture. The Patient is lying
on his/her side on the operating table. The nurse secures the Patient’s position.
The Institute’s doctor cleanses the Patient’s skin in the lumbosacral region. Then,
having drawn 10 ml of the anaesthetic into the hypodermic syringe (lignocaine
1% or marcaine for allergic patients) a thinner needle No. 7 is used to perform
subcutaneous local anaesthesia in the area between the L4 and L5 spinous
processes (it that turns our difficult, the doctor tries an injection a little lower—
L5/S1 or higher—L3/L4). As soon as the operation site is completely numb, the
doctor advances the needle until he can reach the cerebro-spinal fluid. About 5-7
ml of this fluid is transferred into a sterile container, another 1 ml into the 2 ml
hypodermic syringe provided for taking the Product, and 2 ml into another 2 ml
hypodermic syringe to be used again with the lumbar puncture needle after the
Product has been administered.
Next, the Institute’s doctor takes some Product from a supplied sterile container
kept in another container and in a sterile package into a 2 ml hypodermic syringe
already half-filled with 1 ml of the Patient’s cerebro-spinal fluid. The doctor
introduces the Product through the lumbar needle into the subarachnoid space in
the lumbar section of the spinal canal and another hypodermic syringe, the one
containing 2 ml of the cerebro-spinal fluid, is attached to the lumbar needle and
the fluid is injected into the spinal canal “pushing” the Product on. At the final
phase of the operation, the lumbar needle is removed, the place is cleaned with
a disinfection solution and secured with a sterile dressing glued to the skin. Then,
the Patient, sitting in a wheel-chair, is shipped to the ward where he/she is
recommended to lie down for at least 12 hours. The Patient is monitored by the
nurse who keeps the case report form, measures the blood pressure and heart
rate every 30 minutes after administering the Product for 3 hours and then every
3 hours, and measures the body temperature after another 6 hours. After 12-18
hours, the Institute’s doctor assesses the Patient’s condition, orders his/her
verticalisation, and decides that the Patient may be discharged from hospital.
Before each visit at which the procedure is performed, the Patient will be asked
to fill out a health condition questionnaire and to report to the Institute’s doctor
or nurse any changes in his/her health, and all the changes in the medicines
taken.
Also, during 18 months after the Therapy, the Patient will regularly do a
questionnaire for the Institute’s personnel over the phone (patients with speech
problems will use a person authorised for contacts with the Institute). The
questions will lead to describing the current symptoms of disease (using what is
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Cell Therapy Institute S.A., Appendix 3 to the Agreement
known as the ALS-FRS scale) and a medical sociology method known as a ”life
quality assessment.”
What are the benefits of the Therapy?
No benefits can ever be guaranteed. However, literature and earlier research
done in the Department of Neurology and Neurosurgery of the University of
Warmia and Mazury in Olsztyn allow us to expect that mesenchymal stem cells
isolated from Wharton’s jelly in the umbilical cord will produce desired clinical
effect by slowing down the progress of the disease. There are reasons to believe
that the proposed Therapy will offer higher success rate than treatments used so
far.
What are the potential side-effects or risks coming with this Therapy?
The risk is insignificant because no side effects of the Product have been
identified so far. We cannot, however, rule out such potential side-effects as,
e.g., higher body temperature or allergic reactions. Administering the Product
into the cerebro-spinal fluid by lumbar puncture may involve some discomfort or
gentle pain in the lumbar region of the spine and, rather rarely, a stronger pain
radiating to the buttock and leg or, sometimes, some numbness may persist in
that area for several days. This is because the puncture has irritated the nerve
root sitting in the dural sac of the spine’s lumbar section (there is no spinal cord
in this section) and it is usually a temporary sensation. After making the lumbar
puncture but before introducing the Product, a small amount of cerebro-spinal
fluid (5 ml) will be sampled for research purposes. This sample will be tested for
its chemical and cytological properties, as well as for the assessment of any
immune and inflammatory processes. Some patients may (quite frequently) have
a headache or nausea but vomiting is rare. These symptoms are caused by the
reduction of the volume of cerebro-spinal fluid in the subarachnoid space
surrounding the spinal cord and brain and they usually subside within 12-24
hours (the body produces the cerebro-spinal fluid at a rate of 0.3-0.35 ml/minute
so 5 ml can be replenished after about a quarter of an hour). To reduce the risk
of reactions describe above, the Patient should stay in a horizontal position with
head rather low for at least 12-18 hours. This is why the Patient must spend
most of the first 24 hours after the Administration in a hospital environment at
the Institute receiving nursing care and periodical checks by the Institute’s
doctor. The Patients are usually discharged from hospital on the second day after
the Administration, when the doctor in charge decides so. Hospitalisation is
extended only in very rare cases. One of the highly infrequent complications
after lumbar puncture is bleeding into the spinal canal which shows as a quick
reduction of strength and sensibility to touch in the legs, and this condition may
occur during the first 24 hours after the Therapy. We cannot rule out a rather
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Cell Therapy Institute S.A., Appendix 3 to the Agreement
rare allergic reaction to substances used during the treatment and to the Product
itself. A reactive response may also cause a temperature, bad mood, rashes and,
in more serious cases, some breathing and circulatory problems (anaphylactic
reaction). The Patient must, in his/her own interest, inform the doctor and
nurses in the Institute about all his/her previous allergic reactions. Serious
complications which are very rare may require moving the Patient to the
University Clinical Hospital for a more complete diagnosis and, perhaps, also a
conservative or surgical treatment. If such serious complications really occur, the
Institute will provide access to diagnostic examination and treatment at the
University Clinical Hospital in Olsztyn on principles of a mutual agreement with
the Hospital. At a later stage, after the Patient’s discharge from hospital and in
further days and weeks, some symptoms of infection may occur which, albeit
very rare, cannot be ruled out from any medical treatment involving skin
puncture, in this case, made by inserting a needle through the skin into the
subarachnoid space in the lumbar section of the spinal canal. An infection may be
more or less extensive, from local skin reaction, to symptoms of meningitis, an
empyema in the spinal canal and, in a more extreme form, to a general infection
that can cause a sepsis. As a consequence, such infection may damage the spinal
cord which requires surgical intervention and a long treatment with antibiotics to
avert paresis of the limbs or even their paralysis. A generalised infection may be
dangerous for human life. Whenever any unusual pain or symptoms occur,
contact the Institute’s doctor by dialling 600 217 315.
Who performs and supervises the Therapy?
The Product will be administered by the medical team of the Institute. A
volunteer doctor supervised by Professor Wojciech Maksymowicz will be the
Therapy Project Leader. Any questions or problems arising during the Therapy
should be asked and discussed with the Medical Team of the Institute by dialling
517868949, where the Team members are available:
a)
Professor Wojciech Maksymowicz, Ph.D.—neurosurgeon
b)
Dr Joanna Wojtkiewicz, Assistant Professor, University of Warmia and
Mazury—medical biologist, obstetrician
c)
Dr Monika Barczewska, Ph.D.—neurosurgeon
d)
Dr Tomasz Siwek, Ph.D.—neurologist.
The therapy is supervised by the Bioethical Committee of the University of
Warmia and Mazury in Olsztyn.
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Cell Therapy Institute S.A., Appendix 3 to the Agreement
Is participation in the Therapy confidential?
The medical documentation and data of the Patient participating in the Therapy,
which have been collected in connection with the process, can be inspected
according to the current law only by duly authorised persons: a representative of
the University’s Bioethical Committee, members of the Institute’s Medical Team,
and authorities monitoring the activities of Tissue and Cell Banks. All these
institutions/individuals are bound by privacy and confidentiality obligations
concerning the data released to them to the extent defined by the law (Personal
data protection Act of 29-08-1997, the Journal of Laws No. 133, item 883).
The Patient’s data will be stored in a secure way ruling out any unauthorised
access. Whenever the study results are released, e.g., in a published scientific
paper, all the personal and, especially, all the sensitive data of the Patient will be
removed to make his/her identification impossible.
I hereby confirm having read this document.
………………………………………………
Date, signature of the Patient (or the guardian’s signature)
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