Trial Outcomes & Findings for Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis (NCT NCT01363401)

Last Updated: 2022-03-17

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

72 participants

Primary outcome timeframe

baseline(Visit 5) and week 16(Visit 9)

Results posted on

2022-03-17

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	HYNR-CS Inj. Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment No treatment with HYNR-CS inj.
Overall Study STARTED	41	31
Overall Study COMPLETED	39	27
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HYNR-CS Inj. n=41 Participants Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment n=31 Participants 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 n=72 Participants Total of all reporting groups
Age, Continuous	52.59 years STANDARD_DEVIATION 8.59 • n=5 Participants	52.65 years STANDARD_DEVIATION 8.93 • n=7 Participants	52.61 years STANDARD_DEVIATION 8.61 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	13 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment Korea, Republic of	41 participants n=5 Participants	31 participants n=7 Participants	72 participants n=5 Participants
Riluzole use on Riluzole	41 participants n=5 Participants	31 participants n=7 Participants	72 participants n=5 Participants
Riluzole use Not on Riluzole	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline(Visit 5) and week 16(Visit 9)

Population: The ALSFRS-R score was assessed by all the subjects in Phase 1/2 clinical trials.

Outcome measures

Outcome measures
Measure	HYNR-CS Inj. n=39 Participants Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment n=27 Participants No treatment with HYNR-CS inj.
The Difference in the Changes of Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Between Treatment Groups and Control Groups.	-1.36 score on a scale Standard Deviation 2.39	-4.67 score on a scale Standard Deviation 3.25

SECONDARY outcome

Timeframe: baseline(Visit 5) and week 16(Visit 9)

Population: Apple scale was assessed except Two participants of No treatment group, because 1) ICU admissions for breathing therapy 2) Patients reject the measurement.

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)

Outcome measures

Outcome measures
Measure	HYNR-CS Inj. n=39 Participants Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment n=25 Participants No treatment with HYNR-CS inj.
Change in Appel Scale	8.97 point Standard Deviation 9.24	17.96 point Standard Deviation 11.78

SECONDARY outcome

Timeframe: baseline(Visit 5) and week 16(Visit 9)

Population: 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

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)

Outcome measures

Outcome measures
Measure	HYNR-CS Inj. n=38 Participants Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment n=25 Participants No treatment with HYNR-CS inj.
Change in Forced Vital Capacity (FVC) (Percent of Predicted Normal)	-10.51 percent of prediceted Standard Deviation 9.52	-10.75 percent of prediceted Standard Deviation 8.40

SECONDARY outcome

Timeframe: baseline(Visit 5) and week 16(Visit 9)

Population: The SF-36 was assessed except Two participants of no treatment group, because 1) ICU admissions for breathing therapy 2) Patients reject the measurement.

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)

Outcome measures

Outcome measures
Measure	HYNR-CS Inj. n=39 Participants Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment n=25 Participants No treatment with HYNR-CS inj.
Change in SF-36 (The Short Form (36) Health Survey is a 36 Item)	-8.59 point Standard Deviation 12.39	-11.83 point Standard Deviation 11.28

Adverse Events

HYNR-CS Inj.

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

No Treatment

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HYNR-CS Inj. n=41 participants at risk Treatment group with HYNR-CS inj. intrathecal injection with 1ml/10kg of body weight administer twice at an interval of 26day.	No Treatment n=31 participants at risk No treatment with HYNR-CS inj.
Infections and infestations Pyelonephritis acute	2.4% 1/41 • Number of events 1 • 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(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.	0.00% 0/31 • 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(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.
Metabolism and nutrition disorders Hyponatraemia	2.4% 1/41 • Number of events 1 • 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(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.	0.00% 0/31 • 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(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.
Cardiac disorders Cardiac arrest	0.00% 0/41 • 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(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.	3.2% 1/31 • Number of events 1 • 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(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.
Injury, poisoning and procedural complications Contusion, Ankle fracture	0.00% 0/41 • 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(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.	6.5% 2/31 • Number of events 2 • 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(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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.4% 1/41 • Number of events 1 • 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(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.	0.00% 0/31 • 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(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.

Other adverse events

Additional Information

Seung-Hyun Kim, M.D., Ph.D.

Hanyang University Seoul Hospital

Phone: +82-2-2290-8114

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place