Als treatment protocol details

Explanation

The followings are explanations for this clinical study. If you have any questions, please

inquire of the principal investigator, a sub-investigator or a coordinator.

1. Purpose

This clinical study is to develop a new treatment. In this study the autologous marrow-

derived adult stem cell (HYNR-CS1), which is expected to fulfill neuroprotection and

differentiate into the nerve cell, is used as the cytotherapeutic agent. Thus, this study is

focused on studying its efficacy and safety.

2. Methods

This clinical study is to ascertain whether the cytotherapeutic agent ‘HYNR-CS1’ is

clinically effective against muscle weakness and amyotrophy caused by the injury and

destruction of motor neurons in patients with amyotrophic lateral sclerosis (ASL). This

study is limited to the subjects who signed the consent form and are suitable to the

inclusion criteria, and treatments are performed twice, the primary treatment and the

secondary treatment, at intervals of 35 days. Also, the follow-up is performed 3 months

after the primary treatment (2 months after the secondary treatment was completed).

The final judgment is on the authority of the follow-up.

3. Cytotherapeutic Agent and Subjects

A stem cell indicates an undifferentiated cell, which is able to form a specific tissue or

organ after being proliferated or differentiated. The adult stem cell does not make the

tumor, unlike bone marrow transplantation, and can be cultured in vitro. Accordingly, it is

very advantageous to practical treatments.

Additionally it has been known that erythropoietin, effective for nerve growth and

protection, ameliorates the cytothesis of the central nervous system. Particularly in a

recent study, it was turned out to be effective for neuroprotection.

The fundamental treatment for degenerative brain diseases has not been developed yet,

due to the limitation of nervous cytothesis. In recent times, cell replacement therapy has

reared up to overcome the limitation.

The above-mentioned adult stem cell is the autologous bone marrow and is cultured for

about 35 days previously to practical use.

The bone marrow will be harvested twice in all. The cell, made into cytotherapeutic agent

(code name: HYRN-CS1) is intrathecally injected in the form of cell filling fluid diluted with

cerebrospinal fluid.

This clinical study is performed independently by Hanyang University Medical Center,

and it will be carried out for about 24 months with about 20 subjects (22 including the

subjects to be excluded). If you are selected to be a subject, the 100% autologous

marrow-derived adult stem cell will be administered to you. Also there is no possibility

that you may be assigned to the placebo group, in consideration of ethical problems.

4. Procedure

If you determine to participate in this study, your attending doctor will perform a physical

check-up, blood tests and neurophysiological examinations in order to check whether you

are suitable to this study. If you are suitable to the study, you will be assigned to the

experimental group. You need to be hospitalized three times in all, and each hospital

needs 2 days and 3 nights or 3 days and 4 nights. In addition to three hospitalizations,

you should visit the hospital on the days appointed for follow-ups (9 weeks and 13 weeks

after the primary treatment, respectively). Whenever visiting the hospital, you will

undergo an overhaul in order that clinical changes and adverse events may be detected.

5. Nota Bene

You should visit the hospital on the days appointed by the doctor.

Also, you should not participate in another clinical study during the 3 months’ follow-up.

It is important to minimize adverse events caused by other drugs, as well as to evaluate

the efficacy and safety of the agent.

6. Possibility of Adverse Events

The above-mentioned autologous marrow-derived adult stem cell is used to hebetate the

degenerative changes of nerve cells in patients with ASL. Adverse events, reported in

other studies, unknown ones may occur during this clinical study.

7. Expectable Risks and Adverse Events

Hematological changes (abnormal changes in erythrocytes, leukocytes and platelets),

infection or a tumor (related to the stem cell therapy, e.g., teratoma) may occur in the

process of cytotherapy. Also, hematoma may occur in connection with the harvest of the

bone marrow. Local anesthesia may cause an adverse event. And it has been reported

that a headache or a shock may temporarily occur in the process of intrathecal injection.

Such adverse events and inconvenience will be continuously evaluated and corrected by

the attending doctor from start to finish.

The clinical studies, based on cytotherapeutic agents, are very restricted all over the

world, and there is a possibility that unexpected problems may occur.

Adverse events and problems, related to this clinical study, will be immediately reported

to the institutional review board (IRB), and investigators will take measures at its

direction.

If you have any questions, please inquire with PlanetHospital anytime.

Your attending doctor may administer a drug, vitamin or inorganic matter to you if

necessary. However, you should not take other experimental drugs during the follow-up.

8. Advantages

This clinical study is very effective to prove the efficacy of the autologous marrow-

derived stem cell on patients with ALS. Cytotherapeutic agents are restrictedly used for

clinical studies all over the world. If you are selected to be a subject of this study, the

cytotherapeutic agent will be supplied free of charge to you.

9. Other Treatments

Riluzole, the only drug authorized by the U.S. Food and Drug Administration (FDA), and

conservative treatments may be administered. In case you sustain physical damage due

to an immediate cause of this clinical study, it will be immediately reported to IRB and

relevant treatments will be performed for you.

As you know, ALS is characterized by irreversible degeneration, respiratory paralysis and

muscle weakness. So you need to be aware of the fact that the symptoms are

exacerbated even after the cytotherapeutic agent was being administered.

10. Period and Subjects

This clinical study is scheduled to be carried out for about 6 months in all. The first 3

months is to perform cytotherapy, and during the second 3 months, the follow-up will be

performed. About 22 subjects, including you, are scheduled to participate in the study.

The number was determined in consideration of the subjects to cease voluntarily or be

fallen out by the investigator (10%). Thus practically, 20 patients will be subject to this

clinical study.

11. Compensation

There are no compensation administered to patients for participating in this clinical trial

per the laws of South Korea. Furthermore foreigners such as yourselves are responsible

for all hospital and clinical related expenses. As for the expenses, you will pay the

minimum (special treatments, neurologic examinations and neurophysiological

examinations will be performed without charge). But with regard to the cytotherapy to be

performed in this study, you will communicate this matter with PlanetHospital for

coordination.

12. Not Relevant

13. Report

In the event that the news which may affect your participation, is detected during this

clinical study, it will be reported to you or your protector as soon as possible.

14. Notification

If new information, which may affect you, is taken, the investigator will immediately

notify you of it.

15. Inquiry

If you want to take additional information on this clinical study or your rights and

interests, please inquire of the principal investigator, the sub-investigator or the

coordinator (clinical research nurse, CRN). Also if you sustain damage due to this clinical

study, contact the principal investigator or medical workers.

16. Withdrawal

If you want to withdraw the participation in this clinical trial in bodily fear, please tell the

investigator it. If you decided to stop participating halfway, immediately tell the

investigator it and again visit the hospital to undergo the final examination.

In the following cases, the investigator may fall out you without your consent.

- The case where the investigator decides to halt this clinical study.

- The case where a medical problem or a serious adverse event is detected in you.

- The case where it is methodologically impossible to administer the agent to you.

- The case where you do not follow the schedule.

Under no circumstances you will not be disadvantaged, and doctor’s treatments and

attitude will not be changed. However no funds are refunded but any unused

compensation is returned or not requested.

17. Voluntary Participation

If you fully understand the explanation for this clinical study and make a decision to

participate in the study, you should sign the consent form. In this case, you should

voluntarily sign the form and should not do it on compulsion. You may withdraw the

consent anytime even though you signed the consent form. But after you drop out the

clinical study, the agent is administered free of charge anymore.

18. Confidentiality

Your information, medical records and research data will be confidential, and will not be

used publicly. However, they may be used within the framework of relevant laws and

regulations.

The one (IRB), who obtain the approval of the director of Korea FDA or the hospital, may

read your medical records related to this clinical study, in order to review the procedure

of the clinical study and to verify the reliability of data. In this case, it should be done

without infringing confidentiality.

Although the results of this clinical study are carried in a medical journal, your

information will not be opened. After signing the consent form, you, your protector or

your legally-acceptable representative may read your medical records.

After this clinical study was finished, the results will putted in the lockable box appointed

by IRB.

Inclusion and Exclusion Criteria

1. Inclusion Criteria

- Patients aged between 25 and 80

- Patients who were diagnosed with ALS on the authority of EI Escorial Criteria and

comes under probable ALS and upward.

- Those who get 21 points in the ALSFRS-R score.

- Those who can visit the hospital on foot or by help of a protector.

- Patients who or whose protectors signed the consent forms.

2. Exclusion Criteria

- Those who do not correspond to the criteria of ALS.

- Those who correspond to the criteria of ALS but do not consent to the participation in

the clinical study.

- Patients in danger of cytotherapy-related adverse events (the malignant tumor, the

cardiogenic shock, moderate hypertension, etc.).

- Patients whose get ALSFRS-R score is less than 20.

- Patients who were attached to the ventilator or underwent tracheostomy at the time

of selection.

- Patients who underwent gastrostomy at the time of selection.

- Patients whose clinical changes cannot be checked because they could not undergo

the pulmonary function test at the time of selection or whose forced vital capacities

were estimated at 20% and less.

- Patients with serious internal complications.

- Patients who took other experimental drugs 3 months before this clinical study.

- Patients who have the history of postictal phenomena.

- Patients who are pregnant.

Code Name, Principal Ingredient and Administration

Code Name: HYNR-CS1 (the autologous marrow-derived adult stem cell)

Principal Ingredient: The mesenchymal stem cell (1×103 cell/Kg)

Administration

- A dose should be determined according to patients’ weights, and should be diluted

with autologous cerebrospinal fluid, and should be intrathecally injected (twice, at

intervals of about 35 days).

Expectable Adverse Events and Directions for Use

HYNR-CS1

- Hematological Changes (abnormal changes in erythrocytes, leukocytes and platelets)

- Oncogenesis (tumors related to the stem cell therapy, e.g., teratoma)

- Hematoma (in the process of the harvest of the bone marrow)

- Adverse events related to local anesthesia

- The headache and the shock (in the process of intrathecal injection)

Dropout Criteria

- The case where a subject or its legally-acceptable representative asks.

- The case where the investigator judges that the clinical study may have a negative

effect on a subject’s welfare.

- The case where it is difficult to follow up a subject due to poor compliance.

- The case where it is impossible to harvest the bone marrow.

- The case where it is impossible to perform rachicentesis.

Subject Initial Hospital No. ALS Clinic No. Subject No.

ALS_

Screening Protocol

Screening Date of First Visit: y m d Subject No.

Name of Subject Hospital No.

Date of Written Consent y m d Date of Birth y m d

Case History

1) Past and Present History

Name of Disease/Operation Date of Onset(y/m)

Treatment Period(y/m)

Medical Opinion

2) History of ALS

El Escorial criteria

Taking of Rilutek Taken Untaken

Medical Institution of First Diagnosis (y/m) y m d

History of Drugs

Anti-ALS drugs (within 3 months) Taken (refer to the followings) Untaken

Name of Drug

Daily Dose Unit Route

Start of Administration

(y/m/d)

Finish of Administration

(y/m/d)

Continuance of Use Purpose of Treatment

Using

TreatmentPrevention

Using

TreatmentPrevention

Using

TreatmentPrevention

History of Anti-Complication Drugs Taken (refer to the followings) Untaken

Name of Drug

Daily Dose Unit Route

Start of Administration

(y/m/d)

Finish of Administration

(y/m/d)

Continuance of Use Purpose of Treatment

Using

Using

Using


ALS_

Lab findingTest Date Result

Brain MRI

C-spine MRI

Protein & Immunoelectrophoresis

BM Exam

Creatine Kinase

Thyoid function test

Calcium / Phosphate

Parathyroid Hormone

Tumor mekers

Anti-Hu Ab

CT disease markers (ANA, RA, ANCA, C3.4)

Serum VDRL

Anti-HIV Ab

Anti-HTLV-1 Ab

Anti-neural Ag.(GM1, asialo-GM1)

LeukocyteHexosaminidase A assay

CAG repeat(androgen receptor gene)

SerumVery long chain fatty acid

Vit B12

Abdominal Sono.

CSF-Study

other

Muscle Bx:

EMG finding:


ALS_

Follow Up Note

Date PET(FVC) FRSNorris Scale

Appel Score

Neurophysiologic Index Examinator

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

y m d

Time Table

1 st AdmissionSecure Baseline data

1 st Bone Marrow Collection

Application on Admission

Admission Content Attending Worker

1 st

AdmissionDay1

1. Drawing up Informed Consent2. Neurologic Examination3. Drawing up ALS Clinic Patient sheet4. Record Functional Scale 5. CBC, Electrolyte, U/A, EKG, Chest PA

SMA, TFT, PET, Neurophysiologic Examination

Full-Time DoctorProfessor in Charge Full-Time DoctorAttending DoctorNurse SpecialistNurse SpecialistAttending Doctor

Day2

1. 1 st Bone Marrow Collection2. Pharmacovigillance after Bone Marrow

Collection

Full-Time DoctorProfessor in Charge Attending Doctor

Day3

1. Pharmacovigillance after Bone Marrow Collection, Discharge

Attending Doctor

2nd Admission2nd Bone Marrow Collection

1 st HYNR-CS1 Treatment

3rd Admission2 nd HYNR-CS1 Treatment

2nd

AdmissionDay1

1. Neurologic Examination2. Record ALS Clinic Patient sheet 3. Record Functional Scale sheet 4. CBC, Electrolyte, U/A, EKG, Chest PA


5. 2 nd Bone Marrow Collection

Full-Time DoctorAttending DoctorNurse SpecialistNurse SpecialistAttending Doctor

Full-Time DoctorProfessor in Charge

Day2

1. 1 st HYNR-CS1 Treatment2. Post-Treatment Pharmacovigillance

Full-Time DoctorProfessor in ChargeAttending Doctor

Day3

1. Post-Treatment Pharmacovigillance, Discharge

Attending Doctor

3rd

AdmissionDay1

1. Neurologic Examination2. Record ALS Clinic Patient sheet 3. Record Functional Scale sheet4. CBC, Electrolyte, U/A, EKG, Chest PA


Full-Time DoctorAttending DoctorNurse SpecialistNurse SpecialistAttending Doctor

Day2

1. 2 nd HYNR-CS1 Treatment2. Post-Treatment Pharmacovigillance

Full-Time DoctorProfessor in ChargeAttending Doctor

Day3

1. Pharmacovigillance after Autologous Bone Marrow Stem Cell Treatment, Discharge

Attending Doctor

Checklists on Admission

Prescription Name

ALSMSC 1st

Admission (BMextraction)

MSC 2nd

Admission(Stem Cell

1 차 Therapy)

MSC 3rd

Admission(Stem Cell

2 차 Therapy)

Routine Laboratory

Study

Routine CBC Profile(1) (BUN/Cr, Ca, P, TP) Uric acid LDH-CROL HDL-CROL Total-Lipid TG Routine Urine Analysis Sodium Potassium Chloride CPK EKG Chest PA/lat.

Electrophoresis

Protein EP, Serum Protein EP, Urine Immunoelectrophorosis, Serum

Immunoelectrophorosis, Urine

Imaging Study

Brain MRI / c CE C-Spine MRI / c CE

HomoneTSH T4 (free) PTH

Tumor Markers

AFP CA19-9 CEA CA125

SCC NSE PSA CA15-3

Connective Tissue

Disease

RF Anti-cardiolipm Ab AIT titer (ANA) ANCA titer Lupus anti coagulant C4 C3

InfectionHIV VDRL HTLV-1

VitaminVit B12 Folate

Pulmonary PFT (Spirometry) Blood Smear

PB smear

Metal

Aluminum Arsenic Copper, mangane Lead, cadmium

CSF study

Routine Protein Chloride Gic, CSF Gic

Neurophysiologic

Examination

NCV, Motor, U / Extr NCV, Motor, L / Extr NCV, Sensory, U / Extr NCV, Sensory, L / Extr H-reflex F-wave, U / Extr F-wave, L / Extr EMG, U / Extr EMG, L / Extr

Neurologic Examinatio

n

Neurologic Examination

Somatomedin-c Add (Pre/Post-Admission Application)


ALS_

Admission 1

Baseline Data1 st Bone Marrow Collection

Evaluation/Examination List

The followings are to be performed previously to admission.

Procedure Examination List Check

1 The Present State of Informed Consent Yes

2 Physical Checkup Yes

3 Electrocardiography Yes

4 Laboratory Test Yes

5 Medication History Analysis Yes

6 ALS rating scale (Norris, Appel, FRS) Yes

7 Neurologic Exam (Video & Photo) Yes

8 Neurophysiologic Index Yes

9 1 st bone marrow stem cell extraction(HYNR-CS1 Limited to Subjects)

Yes

10 CSF Study Yes

11 SF-36 Yes


ALS_

The Present State of Informed Consent

Written Consent: YES / NO Date: y m d

Physical Checkup

Vital Signs (Pressure / Pulse / Body Temperature / Stature) Date: y m d

Blood pressure (mmHg/ mmHg)

Pulse (bpm) Body Temperature (℃)

Stature (cm) Weight (kg)

Physical Examination

Accompanying Disease YES – Please write down detail NO

Diseases Opinion

Cardiovascular Diseases

Pulmonary and Respiratory Diseases

Gastrointestinal,Hepatic and Biliary

diseases

Endocrine Diseases

Renal and Urinary Diseases

Reproductive Diseases

Musculoskeletal Diseases

Mental Diseases

Allergy

Skin and Connective Tissue

Other Accompanying Diseases


ALS_

Electrocardiography (12-lead ECG)

Date: y m d

Was a significant positive abnormality observed on electrocardiography?

Normal Abnormal => In the case of “Yes”, write down the results and the clinician’s

opinion.

Laboratory Test

Special Examination Date: y m d No Application

Checklists Unit Result Note (opinion)TSH mlU/LFree T4 mg/dlPFT %Somatomedin-C ng/ml

Complete Blood Count Examination (CBC)

Result

Checklists Unit / / / / / / / /WBC (total) X10³cell/mm³RBC X106cell/mm³Hemoglobin g/dlPlatelet X10³cell/mm³Hematocrit %


ALS_

Chemical Examination (Chemistry) Date: y m d No Application

Cheklists Unit Result Note (opinion)

Sodium mg/dl

Potassium mg/dl

Chloride mg/dl

AST(SGPT) units/L

ALT(SGOT) units/L

Alkaline phosphatase

units/L

BUN mg/dl

Creatinine mg/dl

Total bilirubin mg/dl

Albumin g/dl

Phosphorus mg/dl

Triglyceride mg/ml

Total cholesterol mg/dl

Uric acid mg/dl

Calcuim mg/dl

CPK units/L

Glucose mg/dl

LDH units/L

Urinalysis Date: y m d No Application

Checklists Normal Value Result Note (opinion)

pH 4.5 - 8

Albumin -

Glucose -

Ketone -

Bilirubin -

WBC 0-4/HPF

RBC 0-4/HPF


ALS_

Medication History Analysis

Combined Drug

Ingredient (or Product) Name

Administration Route

Daily Dose Indication

Outset of Administratio

n

Completion of

Administration

/ / / / Ongoing

/ / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / / Ongoing

/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing

/ / / / Ongoing

/ / / / Ongoing


ALS_

ALS rating scale (Norris, Appel, FRS)

Application: YES / NO Date: y m d

Bone Marrow Mesenchymal Stem Cell Extraction


CSF Study


Decide whether or not to participate in this Clinical Trial

Check whether this subject can participate in this clinical trial.

Continue Dropout (=> Dropout, Fill out the back in relation to the completion of screening

Evaluation Date: y m d

Signature of Investigator:


ALS_

Admission 3

2nd HYNR-CS therapy




1 The Present State of Informed Consent Yes








9 1 차 bone marrow stem cell extraction(HYNR-CS1 Limited to Subjects)

Yes

10 CSF Study Yes

11 SF-36 Yes

12 Check on Adverse Event Yes


ALS_

Check on History of Combined Drug

Is there a change in combined drug? YES => Write down the changes of combined drugs on the page.

NO

Physical Checkup







Diseases Opinion



Gastrointestinal,Hepatic and Biliary diseases

Endocrine Diseases




Mental Diseases

Allergy




ALS_


Date: y m d



opinion.

Laboratory Test




Result



ALS_



Sodium mg/dl

Potassium mg/dl

Chloride mg/dl

AST(SGPT) units/L

ALT(SGOT) units/L


units/L

BUN mg/dl

Creatinine mg/dl


Albumin g/dl

Phosphorus mg/dl

Triglyceride mg/ml


Uric acid mg/dl

Calcuim mg/dl

CPK units/L

Glucose mg/dl

LDH units/L



pH 4.5 - 8

Albumin -

Glucose -

Ketone -

Bilirubin -

WBC 0-4/HPF

RBC 0-4/HPF


ALS_


Combined DrugIngredient (or Product) Name




n

Completion of Administratio

n / / / / Ongoing

/ / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /


/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing

/ / / / Ongoing

/ / / / Ongoing


ALS_



2 nd HYNR-CS1 therapy


CSF Study


Check on Adverse Event

Did an abnormality occur after the above treatment?

YES / NO=> Write down adverse events on the page


ALS_

Adverse Event

1. Adverse Event Evaluation No Evaluation

Adverse Event 1

Adverse Event 2 Adverse Event 3 Adverse Event 4

Adverse Event

Date of Onset / /Continue / /

Continue / /

Continue / /

Continue

Date of Disappearance / / / / / / / /

Severity of Adverse Event

MildnessModerateness Severeness Death

Mildness Moderateness Severeness Death



Result of Adverse Event

Disappeared Recovering Going on Death




Relationship with Adverse Event

Obviously Related Related Possible Inappreciative




2. Results of Clinically-Significant Abnormality Application of Examination

y m d

y m d

y m d

y m d


ALS_

Ambulatory Care 1













ALS_

Physical Checkup







Diseases Opinion




Endocrine Diseases




Mental Diseases

Allergy




ALS_


Date: y m d



opinion.

Laboratory Test




Result



ALS_



Sodium mg/dl

Potassium mg/dl

Chloride mg/dl

AST(SGPT) units/L

ALT(SGOT) units/L


units/L

BUN mg/dl

Creatinine mg/dl


Albumin g/dl

Phosphorus mg/dl

Triglyceride mg/ml


Uric acid mg/dl

Calcuim mg/dl

CPK units/L

Glucose mg/dl

LDH units/L



pH 4.5 - 8

Albumin -

Glucose -

Ketone -

Bilirubin -

WBC 0-4/HPF

RBC 0-4/HPF


ALS_






n


n / / / / Ongoing

/ / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /


/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing

/ / / / Ongoing

/ / / / Ongoing


ALS_







ALS_

Adverse Event


Adverse Event 1


Adverse Event


Continue / /

Continue / /

Continue


















y m d

y m d

y m d

y m d


ALS_

Ambulatory Care 2













ALS_

Physical Checkup







Diseases Opinion




Endocrine Diseases




Mental Diseases

Allergy




ALS_


Date: y m d



opinion.

Laboratory Test




Result



ALS_



Sodium mg/dl

Potassium mg/dl

Chloride mg/dl

AST(SGPT) units/L

ALT(SGOT) units/L


units/L

BUN mg/dl

Creatinine mg/dl


Albumin g/dl

Phosphorus mg/dl

Triglyceride mg/ml


Uric acid mg/dl

Calcuim mg/dl

CPK units/L

Glucose mg/dl

LDH units/L



pH 4.5 - 8

Albumin -

Glucose -

Ketone -

Bilirubin -

WBC 0-4/HPF

RBC 0-4/HPF


ALS_






n


n / / / / Ongoing

/ / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /


/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing

/ / / /

Ongoing

/ / / /

Ongoing

/ / / / Ongoing

/ / / / Ongoing


ALS_







ALS_

Adverse Event


Adverse Event 1


Adverse Event


Continue / /

Continue / /

Continue


















y m d

y m d

y m d

y m d


ALS_

Ambulatory Care 3













ALS_

Physical Checkup







Diseases Opinion




Endocrine Diseases




Mental Diseases

Allergy




ALS_


Date: y m d



opinion.

Laboratory Test




Result



ALS_



Sodium mg/dl

Potassium mg/dl

Chloride mg/dl

AST(SGPT) units/L

ALT(SGOT) units/L


units/L

BUN mg/dl

Creatinine mg/dl


Albumin g/dl

Phosphorus mg/dl

Triglyceride mg/ml


Uric acid mg/dl

Calcuim mg/dl

CPK units/L

Glucose mg/dl

LDH units/L



pH 4.5 - 8

Albumin -

Glucose -

Ketone -

Bilirubin -

WBC 0-4/HPF

RBC 0-4/HPF


ALS_






n


n / / / / Ongoing

/ / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /

Ongoing / / / /


/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing / / / /

Ongoing

/ / / /

Ongoing

/ / / / Ongoing

/ / / / Ongoing


ALS_







ALS_

Adverse Event


Adverse Event 1


Adverse Event


Continue / /

Continue / /

Continue


















y m d

y m d

y m d

y m d


ALS_

End of the Clinical Trial / Dropout

Outset of Clinical Trial: y m d

Completion of Clinical Trial: y m d

YES

NO => Date of Dropout y m d

* Time of Dropout Visit 1 Visit 2 Visit 3

* Reason In case a subject breached inclusion criteria or exclusion criteria Adverse Event / Serious Adverse Event In case a subject asks for secession from the clinical trial Failure of Follow-up In case an investigator has judged that the clinical trial should

be stopped

Overall Opinion

Evaluation Date: y m d

Signature of Investigator:

Als treatment protocol details

Health & Medicine

purposethis clinical

methodsthis clinical

recent study

stem cell therapy

undifferentiated cell

clinical changes

subjectsa stem cell

clinical studies