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Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis

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ClinicalTrials.gov Identifier: NCT01363401
Recruitment Status : Completed
First Posted : June 1, 2011
Results First Posted : July 20, 2016
Last Update Posted : October 9, 2018
Sponsor:
Information provided by (Responsible Party):
Corestem, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Amyotrophic Lateral Sclerosis
ALS
Interventions Biological: HYNR-CS inj
Other: Control group
Enrollment 72
Recruitment Details Between March 2011 to May 2013, Of 10 subjects who consented to participate in the Stage 1 study, 2 subjects failed in screening, and 8 subjects were enrolled in the study. Among 71 subjects who consented to participate in the Stage 2 study, 7 subjects failed in screening, and 64 subjects were randomized.
Pre-assignment Details Phase 1 : March 17, 2011 to November 24, 2011 Phase 2 : December 5, 2011 to May 6, 2013 The study consisted of stage 1 for safety evaluation and stage 2 for efficacy and safety evaluation of the study drug, and at stage 1, safety evaluation of the study drug, and at stage 1, safety evaluation for 28 days and then they followed stage 2.
Arm/Group Title HYNR-CS Inj. No Treatment
Hide Arm/Group Description

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.
Period Title: Overall Study
Started 41 [1] 31
Completed 39 27
Not Completed 2 4
[1]
Including 8 subjects of Phase 1 safety assessment. (Called "Modified ITT" in this clinical trials)
Arm/Group Title HYNR-CS Inj. No Treatment Total
Hide Arm/Group Description

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.

Take each 50mg 1 hour before a meal or 2 hours after a meal at least at an interval of 12 hours, 28 weeks(12 weeks of run-in phase plus 16 weeks of treatment phase)

Total of all reporting groups
Overall Number of Baseline Participants 41 31 72
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 31 participants 72 participants
52.59  (8.59) 52.65  (8.93) 52.61  (8.61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 31 participants 72 participants
Female
17
  41.5%
18
  58.1%
35
  48.6%
Male
24
  58.5%
13
  41.9%
37
  51.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Korea, Republic of Number Analyzed 41 participants 31 participants 72 participants
41 31 72
Riluzole use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 41 participants 31 participants 72 participants
on Riluzole 41 31 72
Not on Riluzole 0 0 0
1.Primary Outcome
Title The Difference in the Changes of Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R) Between Treatment Groups and Control Groups.
Hide Description ALSFRS-R is ordinal rating scale questionnaire (rating 0-4 for each question, 4 is most functional, 0-48 total) of 12 functional activities. The most functional total score is 48. ALSFRS-R was evaluated at baseline and week 28.(The first injection was performed at 0 week) ALSFRS-R total score variation baseline(Visit 5) and week 16(Visit 9)
Time Frame baseline(Visit 5) and week 16(Visit 9)
Hide Outcome Measure Data
Hide Analysis Population Description
The ALSFRS-R score was assessed by all the subjects in Phase 1/2 clinical trials.
Arm/Group Title HYNR-CS Inj. No Treatment
Hide Arm/Group Description:

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.
Overall Number of Participants Analyzed 39 27
Mean (Standard Deviation)
Unit of Measure: score on a scale
-1.36  (2.39) -4.67  (3.25)
2.Secondary Outcome
Title Change in Appel Scale
Hide Description

To evaluate the disease change, Appel scale will be assessed. Appel scale is a test tool, which is devised to evaluate the functional condition and variation of ALS(Lou Gehrig’s disease) patients (rating 6 to between 30 and 36 points for each of 5 functional conditions, 30-164 total).

The higher the total score presents more severe disability. This was done at Visit 1, Visit 5 and Visit 9 (week -12,0,16). The first injection was performed at 0 week(Visit 5) Appel scale total score variation baseline(Visit 5) and week 16(Visit 9)

Time Frame baseline(Visit 5) and week 16(Visit 9)
Hide Outcome Measure Data
Hide Analysis Population Description
Apple scale was assessed except Two participants of No treatment group, because 1) ICU admissions for breathing therapy 2) Patients reject the measurement.
Arm/Group Title HYNR-CS Inj. No Treatment
Hide Arm/Group Description:

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.
Overall Number of Participants Analyzed 39 25
Mean (Standard Deviation)
Unit of Measure: point
8.97  (9.24) 17.96  (11.78)
3.Secondary Outcome
Title Change in Forced Vital Capacity (FVC) (Percent of Predicted Normal)
Hide Description

Secondary efficacy was measured by comparing the rate of decline of mean FVC by treatment group.

FVC which is a clinical scale to observe variation in patient’s respiratory competence, was conducted at Visit 1, Visit 5 and Visit 9. (week -12,0,16) The first injection was performed at 0 week. FVC variation baseline(Visit 5) and week 16(Visit 9)

Time Frame baseline(Visit 5) and week 16(Visit 9)
Hide Outcome Measure Data
Hide Analysis Population Description

One of the test group, FVC was assessed except because received tracheostomy during the clinical trial.

FVC was assessed except Two participants of no treatment group because 1) ICU admissions for breathing therapy 2) Patients reject the measurement

Arm/Group Title HYNR-CS Inj. No Treatment
Hide Arm/Group Description:

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.
Overall Number of Participants Analyzed 38 25
Mean (Standard Deviation)
Unit of Measure: percent of prediceted
-10.51  (9.52) -10.75  (8.40)
4.Secondary Outcome
Title Change in SF-36 (The Short Form (36) Health Survey is a 36 Item)
Hide Description

The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score presents more severe disability. The higher the score presents less disability.

This was measured at Visit 5 and Visit 9. (week 0,16) The first injection was performed at 0 week.

The score variation baseline(Visit 5) and week 16(Visit 9)

Time Frame baseline(Visit 5) and week 16(Visit 9)
Hide Outcome Measure Data
Hide Analysis Population Description
The SF-36 was assessed except Two participants of no treatment group, because 1) ICU admissions for breathing therapy 2) Patients reject the measurement.
Arm/Group Title HYNR-CS Inj. No Treatment
Hide Arm/Group Description:

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.
Overall Number of Participants Analyzed 39 25
Mean (Standard Deviation)
Unit of Measure: point
-8.59  (12.39) -11.83  (11.28)
Time Frame Adverse events (AEs) were collected for the duration of the study period: March 2011 to May 2013. Each subject was followed for AEs from consent signing to the end of their study participation.
Adverse Event Reporting Description

Adverse event(AE) means undesirable and unintended sign(e.g. abnormal laboratory test value) or symptom, or disease which appears following Investigational Drug use, and it shall not have causal relationship with the drug, necessarily.

And then result of adverse events includes all the adverse events observed in 1/2 clinical trials.

 
Arm/Group Title HYNR-CS Inj. No Treatment
Hide Arm/Group Description

Treatment group with HYNR-CS inj.

intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.

No treatment with HYNR-CS inj.
All-Cause Mortality
HYNR-CS Inj. No Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
HYNR-CS Inj. No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/41 (7.32%)      3/31 (9.68%)    
Cardiac disorders     
Cardiac arrest  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Infections and infestations     
Pyelonephritis acute  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Injury, poisoning and procedural complications     
Contusion, Ankle fracture  1  0/41 (0.00%)  0 2/31 (6.45%)  2
Metabolism and nutrition disorders     
Hyponatraemia  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
HYNR-CS Inj. No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/41 (68.29%)      22/31 (70.97%)    
Cardiac disorders     
Cardiac arrest  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Ear and labyrinth disorders     
Cerumen impaction  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Eye disorders     
Conjunctival disorder  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Foreign body sensation in eyes  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  4/41 (9.76%)  4 2/31 (6.45%)  2
Nausea  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Toothache  1  1/41 (2.44%)  2 0/31 (0.00%)  0
Diarrhoea  1  1/41 (2.44%)  1 1/31 (3.23%)  1
Dyspepsia  1  0/41 (0.00%)  0 2/31 (6.45%)  2
Abdominal distension  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Abdominal pain  1  1/41 (2.44%)  1 0/31 (0.00%)  0
General disorders     
Influenza like illness  1  8/41 (19.51%)  11 7/31 (22.58%)  8
Pyrexia  1  5/41 (12.20%)  6 1/31 (3.23%)  1
Pain  1  3/41 (7.32%)  4 0/31 (0.00%)  0
Oedema peripheral  1  1/41 (2.44%)  1 1/31 (3.23%)  1
Chest discomfort  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Chest pain  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Hepatobiliary disorders     
Hepatobiliary disorders  1  3/41 (7.32%)  3 0/31 (0.00%)  0
Hyperbilirubinaemia  1  2/41 (4.88%)  2 0/31 (0.00%)  0
Hepatitis toxic  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Infections and infestations     
Gingivitis  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Cystitis  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Periodontitis  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Pyelonephritis acute  1  1/41 (2.44%)  2 0/31 (0.00%)  0
Tinea pedis  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Urinary tract infection  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Vaginitis bacterial  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Injury, poisoning and procedural complications     
Contusion  1  2/41 (4.88%)  2 1/31 (3.23%)  1
Procedural pain  1  1/41 (2.44%)  1 1/31 (3.23%)  1
Ankle fracture  1  0/41 (0.00%)  0 1/31 (3.23%)  2
Investigations     
Alanine aminotransferase increased  1  2/41 (4.88%)  2 0/31 (0.00%)  0
Aspartate aminotransferase increased  1  2/41 (4.88%)  3 0/31 (0.00%)  0
Blood cholesterol increased  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Weight decreased  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Hypokalaemia  1  1/41 (2.44%)  5 0/31 (0.00%)  0
Hyponatraemia  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  9/41 (21.95%)  16 0/31 (0.00%)  0
Arthralgia  1  1/41 (2.44%)  1 1/31 (3.23%)  1
Coccydynia  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Musculoskeletal pain  1  5/41 (12.20%)  5 3/31 (9.68%)  4
Pain in extremity  1  3/41 (7.32%)  3 2/31 (6.45%)  2
Joint swelling  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Neck pain  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Temporomandibular joint syndrome  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Nervous system disorders     
Headache  1  4/41 (9.76%)  5 2/31 (6.45%)  3
Dizziness  1  4/41 (9.76%)  4 1/31 (3.23%)  1
Psychiatric disorders     
Insomnia  1  1/41 (2.44%)  1 2/31 (6.45%)  2
Sleep disorder  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Renal and urinary disorders     
Nephrolithiasis  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Urinary retention  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Reproductive system and breast disorders     
Reproductive system and breast disorders  1  1/41 (2.44%)  2 0/31 (0.00%)  0
Pelvic pain  1  1/41 (2.44%)  2 0/31 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Cough  1  1/41 (2.44%)  2 0/31 (0.00%)  0
Atelectasis  1  2/41 (4.88%)  2 0/31 (0.00%)  0
Reflux larngitis  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Urticaria  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Surgical and medical procedures     
Wisdom teeth removal  1  0/41 (0.00%)  0 1/31 (3.23%)  1
Vascular disorders     
Hypertension  1  1/41 (2.44%)  2 0/31 (0.00%)  0
Hypotension  1  1/41 (2.44%)  1 0/31 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Seung-Hyun Kim, M.D., Ph.D.
Organization: Hanyang University Seoul Hospital
Phone: +82-2-2290-8114
EMail: kimsh1@hanyang.ac.kr
Layout table for additonal information
Responsible Party: Corestem, Inc.
ClinicalTrials.gov Identifier: NCT01363401     History of Changes
Other Study ID Numbers: HYNR_CS_ALS201
First Submitted: May 30, 2011
First Posted: June 1, 2011
Results First Submitted: December 8, 2015
Results First Posted: July 20, 2016
Last Update Posted: October 9, 2018