Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
The purpose of this study is to evaluate the safety and efficacy of autologous bone marrow-derived stem cells("HYNR-CS inj"), through intrathecal delivery for the treatment in patients with ALS.
This study consists of 2 steps. First step is a safety study of the intrathecal(IT) injection of "HYNR-CS inj" in 8 patients with ALS. In this phase 1 study, AE, laboratory test, physical examination, vital signs, Electrocardiogram, and Chest X-Ray examination were evaluated in terms of safety.
Second step is to compare the efficacy and safety between test group and control group of total 64 patients with ALS.
Amyotrophic Lateral Sclerosis
Biological: HYNR-CS inj
Other: Control group
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Phase I/II Trial for Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis|
- The Difference in the Changes of Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Between Treatment Groups and Control Groups. [ Time Frame: 28 weeks (12-week lead-in period + 16-week treatment and follow-up period) ] [ Designated as safety issue: No ]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 between baseline(Visit 5) and 12 weeks following second administration(Visit 9)
- Change in Appel Scale [ Time Frame: week -12,0,16 ] [ Designated as safety issue: No ]
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 6~36 for functional condition, 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 Appel scale total score variation between baseline(Visit 5) and 12 weeks following second administration(Visit 9)
- Change in Forced Vital Capacity (FVC) (Percent of Predicted Normal) [ Time Frame: week -12,0,16 ] [ Designated as safety issue: No ]
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 between baseline(Visit 5) and 12 weeks following second administration(Visit 9)
- Change in SF-36 (The Short Form (36) Health Survey is a 36 Item) [ Time Frame: week 0, 16 ] [ Designated as safety issue: No ]
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 between baseline(Visit 5) and 12 weeks following second administration(Visit 9)
|Study Start Date:||February 2011|
|Study Completion Date:||August 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Test group
Treatment group with HYNR-CS inj.
Biological: HYNR-CS inj
Intrathecal injection with 1ml/10kg of body weight at an interval of 26 days.
Experimental: Control group
No treatment with HYNR-CS inj.
Other: Control group
No treatment of HYNR-CS inj
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by motor neuron loss. Despite of many trials for disease-modifying, no treatment has so far changed natural course of disease.
We have performed the pre-clinical and clinical studies using autologous bone marrow-derived stem cells in ALS. We could get the evidence that autologous bone marrow-derived stem cells have dose-dependent effects on SOD1 mice via intrathecal injection. In our results of clinical trial, intrathecal injection of autologous bone marrow-derived stem cells could slow down disease progression and might be used as a disease modifying strategy in patients with ALS.
This study was designed as a single center, randomized, open-label, parallel-group, 2-stage study, and targeted at patients diagnosed with Amyotrophic Lateral Sclerosis(Lou Gehrig's disease). The study consisted of Stage-1 study for safety evaluation and Stage-2 study for efficacy and safety evaluation of the study drug, and at Stage 1, 7 subjects eligible for the inclusion/exclusion criteria received safety evaluation for 28 days of study drug administration in twice under the protocol, and then followed Stage 2. To decide whether the study can be proceeded in 2 stages, ADR(CTCAE Version 3.0, ≥grade 3) should not appear in initial 7 subjects.
Data obtained from subjects of this study were analyzed into three: Safety Analysis, ITT(Intent-To-Treat) Analysis, and PP(Per Protocol) Analysis. However, in case of phase 1, only safety analysis was conducted, and in case of phase 2, all of safety, ITT, and PP analyses were conducted.
For ITT Analysis, all the subjects whose data on primary efficacy endpoint could be obtained following the administration of investigational drug were analyzed in analysis among subjects who were administered the investigational drug once at least. Also, Modified ITT Analysis, including 7 subjects at Stage 1, was carried out.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01363401
|Korea, Republic of|
|Hanyang University Hospital|
|Seoul, Korea, Republic of, 133-792|
|Principal Investigator:||Seung Hyun Kim, M.D., Ph.D.||Hanyang University|