自体骨髓源性干细胞治疗肌萎缩脊髓侧索硬化症安全性和有效性研究临床试验

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Safety and Efficacy Study of Autologous Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
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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) transplantation of "HYNR-CS inj" in 7 patients with ALS. Safety will be evaluated with adverse effect and clinical.... H! _# F' @2 _8 E
Date First Received: May 30, 2011* v. m( T. _9 f! r
Last Updated: May 30, 2011( Q5 g9 p! P, [( a( b
Verified by: Corestem, Inc., May 2011. N/ C! a8 E3 \* ]0 v8 h& i4 F4 e
Clinical Trial Phase: Phase 1/Phase 2 | Start Date: February 2011
. E+ M; @" k+ ^3 b- D+ Y0 ]Overall Status: Recruiting9 _8 M4 Q' k5 |. N* t
Estimated Enrollment: 716 Z( n5 n1 E8 ?+ A/ m5 u) t$ i
Brief Summary
$ e) d# |; t' J" @8 yOfficial 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”
' L, t5 y( R+ R0 E* XCondition Keyword(s):0 I5 c& u$ I. ~! j- ^7 G
•        Amyotrophic Lateral Sclerosis . J+ Q1 t; b5 N& e
•        ALS
! u; B" R" {9 I& ?& v& ?Additional Keyword(s) Provided by Clinical Trial Investigators:
# j# w, f$ Z7 a( K•        Amyotrophic lateral sclerosis
2 D% N/ R+ F: C- l* \4 `$ X$ M( r•        ALS
$ I' T& J: o. e0 y& g•        Motor neuron disease
( ]  A: S4 H, @7 N9 k•        MND
, ^5 k9 U; Q+ H; P' U•        HYNR-CS inj + X/ K8 ?3 q. U/ W9 R* L7 |* r
•        Autologous bone marrow derived stem cell 4 j( A6 z5 @$ S8 e* b) u/ n; B
•        Intrathecal injection 2 o- O$ v! ?' J" Q
Intervention(s):6 E0 O0 f1 D9 H1 a9 T, {
•        Biological: HYNR-CS inj
. M* Q- Y- a" F! D- f•        Biological: Control group 3 d% i6 M" a; U2 H' @( Y+ t$ P' p" u" ~

$ G$ D9 P' Y9 S7 `0 J0 C* k" ^Condition MeSH Term(s), Assigned with an Experimental Algorithm:
2 z' _0 `5 K7 V: L: H•        Amyotrophic Lateral Sclerosis
# Z. t. i: k0 p; s6 ?•        Sclerosis
0 P. X+ f9 U& g* a•        Motor Neuron Disease 2 d# \  a1 Z& G& D; i# k3 K
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.6 f4 q# [1 b, S7 I& F9 J
This study consists of 2 steps. First step is a safety study of the intrathecal(IT) transplantation of "HYNR-CS inj" in 7 patients with ALS. Safety will be evaluated with adverse effect and clinical laboratory test.0 D" f- S7 v. ?& y
Second step is to compare the efficacy and safety between test group and control group of total 64 patients with ALS.* [# ^5 N% ^% F( ?
Study Type: Interventional
# d" c! k8 ~! r& vStudy Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
- A# r* ?1 s5 `' H* B5 d: \: ?Study Primary Completion Date: July 2012
. E% j  D. z8 s1 ~9 b9 v$ DDetailed Clinical Trial Description
1 u2 N$ P2 r1 A% o& K% g, B- S2 u. r7 J4 WAmyotrophic 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.
# q. q& u  ^& XWe 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.! _' v' R' w* Z9 a3 c- ^! E7 p* f
This study is to evaluate safety and efficacy of HYNR-CS inj(autologous bone marrow-derived stem cells) in patients with ALS.
! Q# G# h$ g* Z6 Z; _( MIntervention(s) in this Clinical Trial( {& [/ c. w1 U' P
•        Biological: HYNR-CS inj
; B/ Y" X6 X( R8 Q/ mo        Intratheca injection with 1ml/10kg of body weight at an interval of 26 days." D9 _5 e4 y* U# ^+ I: W9 G& C
•        Biological: Control group
3 O1 L5 s# b& Z8 b0 S5 ?( T7 y9 So        No treatment of HYNR-CS inj
* y/ d7 r5 _# X# G# G& OArms, Groups and Cohorts in this Clinical Trial, l4 C% V+ Q1 d% g4 A) a
•        Experimental: Test group ; o# P4 ^2 a* b6 v6 G- B
o        Treatment group with test drug.+ }/ w& g6 [  k9 @4 k
•        Experimental: Control group % u8 N! k( ~4 v" N. ^0 U9 |
o        No treatment with HYNR-CS inj.
& k4 s3 }! ?1 @5 E3 N5 c9 T, BOutcome Measures for this Clinical Trial
; A1 r$ {( F  ]( W. j6 u( m2 vPrimary Measures- s) x+ G& N2 C# R7 O2 H
•        Changes in ALSFRS-R score , y. }; y+ w/ N7 @! w
o        Time Frame: Week 12, -8, -4, 0, 4, 8, 12, 16
+ K/ J" l8 V9 h/ M( ?( y' HSafety Issue?: No4 d5 N1 f) ^- s' d/ S# P
Secondary Measures
6 C5 {- N0 P/ `' }( t2 x•        Change in Appel scale # W0 a  j8 y, g; ]/ L
o        Time Frame: Week -12, 0, 16
" v, ^0 p+ j( s. y$ s# o, zSafety Issue?: No
# c6 A2 u# V: L+ `6 @•        Change in FVC ; h3 u* v. v8 E  Y6 e4 B% z
o        Time Frame: Week -12, 0, 16
; i0 w4 X) [. n, aSafety Issue?: No
& x6 C; z2 p" N5 o•        Change in SF-36
0 ^8 v  _- M' _/ Z6 X6 po        Time Frame: Week 0, 166 W7 U0 ?1 t% T: j6 K& D  G
Safety Issue?: No
( K( D0 i$ c* vCriteria for Participation in this Clinical Trial
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2 p" p9 L; s9 J% @0 a* hInclusion Criteria:
3 Y; M: C4 T) H& d8 \4 N! s•        Patients between 25 and 65 years old
2 \* N) J; w3 L" l: \6 L3 B( z•        Patients who have both signs of lower motor neuron(LMN) and upper motor neuron(UMN) degeneration by clinical, electrophysiological or neuropathologic examination 2 a+ \9 u  {6 I
•        Patients diagnosed as 'Probable' or 'Definite' ALS according to the World Federation of Neurology El Escorial criteria : q4 j$ J+ S* _: e( c
•        Patients who have taken Rilutek at stable background dose from 3 months ago at least before screening entry
1 k* D3 e% K5 Y; Z% \1 H, Z6 o•        Patients whose duration of disease is within 5 years from the first diagnosis / j& w" j3 U6 O1 B9 p% G
•        Patients with ALSFRS-R score within 31 to 46 at screening - |! L8 `2 q$ E4 s0 a* X. [9 E2 c
•        Patients who can visit to a hospital by walk personally or by protector's help
  G) |( ]4 p1 [% @& h* M5 U& w6 A•        Patients who provide the written consent by oneself or his/her legal representative
8 z4 }# G0 X3 @$ i; z5 I' mExclusion Criteria:
, Z- L+ k/ z8 T2 [4 W  o•        Patients who doesn't appropriate to the diagnostic criteria of ALS
1 i5 ~& B, j; }0 O•        Patients who are diagnosed as primary lateral sclerosis(PLS) or progressive muscular atrophy(PMA) - J0 T' A  i" M# [) K7 z+ V5 D
•        Patients suspected of adverse effect after stem cell injection(patients suspected of malignant tumor, risk group of psychogenic shock, patients with serious hypertension) : G% d% a2 t+ g# @$ C. @
•        Patients with ALSFRS-R score below 30 at screening ' x% u7 W5 v; h7 u; o% @1 I" ]0 t
•        Patients performed ventilator or tracheostomy at screening & `) G; L+ H3 S! N
•        Patients performed gastrostomy at screening 9 H. x1 k& M5 U# \
•        Patients unable to assess the efficacy of this clinical trial due to unattainable
  m+ a/ q" E) g+ `# C0 w( G1 }1 ]+ q•        PFT(Pulmonary Functional Test) or patients with suspected 40% or less of FVC at screening " A4 b  Z  e6 [( }& F
•        Patients with finding of myocardial infarction or angina pectoris according to ECG, patients who have been performed Stenting or Bypass operation at screening
4 B& \& U; K4 v1 q/ j•        Patients who have taken any other drug for clinical trial within the past 3 months at screening entry 8 D( \$ K- @8 K- P$ t
•        Patients with epilepsy
7 U0 f. g2 \4 N4 c; p# e, v•        Patients with severe renal dysfunction(serum creatinine≥2.0mg/dl)
+ i( h6 c% m; u; C2 x) e9 U1 p! e7 x•        Patients with severe liver dysfunction(ALT, AST, bilirubin≥upper limit of normal X 2) - W( j: t1 |: e& }
•        Pregnant woman, lactating woman, female patients who has a pregnancy planning or who doesn't agree with adoption of contraception methods proper medically, male patients who doesn't agree with adoption of contraception methods proper to his partner during participating this study
" ]! ]8 ~. D+ w7 o( t) Q•        Patients with hemorrhagic tendency at screening
' `% }/ h: I8 N•        Patients with virus infection at screening
& ^9 {& u6 C% t- y+ z•        Patients with a known history of hypersensitivity/allergy to penicillin and streptomycin
4 ]4 D  @( I3 f4 R; W•        Patients with previous stem cell therapy ! t, v+ |4 O; h$ }% y9 P1 M: r
•        Patients diagnosed with cancer 8 P$ |! p9 l2 x, @
•        Patients who have taken any drug thag can effect to bone marrow function
) |4 J+ j! K* F3 W& _•        Patients with any other neurological disease except ALS # ^* p' ]- o' D" {
•        Patients with psychotic diseases
3 o3 n0 I- Z$ G: AGender Eligibility for this Clinical Trial: Both9 R; e& X; K, ^9 }
Minimum Age for this Clinical Trial: 25 Years
5 X7 [3 ?: L( T2 q+ Y6 MMaximum Age for this Clinical Trial: 65 Years( {$ s' C) d$ g% a- @" D! `4 @
Are Healthy Volunteers Accepted for this Clinical Trial?: No
0 T" H( W  |1 T6 ?2 k) ?Clinical Trial Investigator Information4 Z2 u6 _7 i6 x/ B  a! `" b: e
Lead Investigator: Corestem, Inc. Industry
6 K% V& i) t+ KOverall Clinical Trial Officials and Contacts4 c& t4 g9 _; J) w* F# b
Seung Hyun Kim, M.D., Ph.D. Principal Investigator Hanyang University  : b% r6 u# _) \7 m" @" K
Overall Contact: Seung Hyun Kim, M.D., Ph.D. +82-2-2290-9367 kimsh1@hanyang.ac.kr
) Z4 i. f9 B" z- v; p. Q: uRelated Publications
6 U- J: i1 b$ u; q4 ~  ~% s& EReferences' K: `1 @1 X2 ~7 n
Kim H, Kim HY, Choi MR, Hwang S, Nam KH, Kim HC, Han JS, Kim KS, Yoon HS, Kim SH. Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice. Neurosci Lett. 2010 Jan 14;468(3):190-4. Epub 2009 Oct 29.
/ [2 D* T, g6 [$ Y  c' d% ~Choi MR, Kim HY, Park JY, Lee TY, Baik CS, Chai YG, Jung KH, Park KS, Roh W, Kim KS, Kim SH. Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis. Neurosci Lett. 2010 Mar 19;472(2):94-8. Epub 2010 Feb 1.- H! P! R. ?6 O  Q+ E( c8 ^- }. B0 G: c
Additional Information1 z: w" c+ z' {7 B% P6 x
Information obtained from ClinicalTrials.gov on May 31, 20114 ~5 }+ k* f& O" X2 F
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01363401: u0 Z0 J$ l+ ^  e
Study ID Number: HYNR_CS_ALS201: b2 }* d+ ]& Q" A( m' z
ClinicalTrials.gov Identifier: NCT01363401
5 o+ [: Z/ D7 d3 c* Y5 t$ R+ T7 oHealth Authority: Korea: Food and Drug Administration" ?: j9 j6 |) ~- R  S$ ~
Hanyang Cell Therapy Center 4 {% I. `3 w  D
CORESTEM Inc. 8 k1 B; W5 _2 R! M4 ^
Clinical Trials Authorship and Review4 _3 c6 c3 d4 P( T+ P. z
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
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