Prochymal治疗GVHD 的临床研究

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哥伦比亚的诊疗公司Osiris于2012年5月17日宣布获得加拿大卫生部对其干细胞疗法药物Prochymal的上市批准，用于治疗儿童移植物抗宿主病（GVHD）
  k# @' {& |) q  @当前临床进展：; r1 n. X( r2 U5 o/ R
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临床入选方案：9 b& S: U" o) v/ ~% `
Eligibility1 B/ a0 v  T* e0 H( Q3 J
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Ages Eligible for Study:          12 Years to 35 Years
4 m# o& K6 n& e8 Y$ ^Genders Eligible for Study:          Both
% d! @( [/ q& }) `# gAccepts Healthy Volunteers:          No# A) {- f  V5 H2 v" ]* U- W
Criteria
* O3 v/ q5 }$ [* \Inclusion Criteria:
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- o6 J) C( B+ F8 i6 CSubject must have a diagnosis of type 1 diabetes mellitus based on the ADA criteria0 X1 p# o) _2 S* c' q# C" e8 z2 [5 a
Subject must be screened between 2 and 20 weeks from initial T1DM diagnosis! b+ S* s& s6 a3 ]1 X3 {# M% o
Subject must be between the ages of 12 and 35 (inclusive)
5 c/ z- q0 K/ h# ]5 f5 L0 oSubject must have at least one diabetes-related autoantibody present (either GAD or IA-2)
; f- W* M' l$ [+ S4 s, dSubject must have some beta cell function as determined by C-peptide testing
& X- E  x. M) P% i7 @' _Subject must be willing to comply with "intensive diabetes management" as directed by the Investigator with the goal of maintaining blood glucose as close to normal as possible
8 `4 m: C- z# o2 Z$ h+ x. i1 ~Subject must be willing to comply with the schedule of study visits and protocol requirements. C5 e+ i7 l' S7 ]$ H8 ^
Exclusion Criteria:* }9 R6 _% n& x- {4 \1 o

' r- i; b' `4 M% j0 G; PSubject has Body Mass Index (BMI) ≥ 30  U6 Y1 x7 H# h: k8 n5 V. l
Subject has evidence of retinopathy at baseline
4 x' F" \+ }2 c3 Z) ^Subject has abnormally high lipid levels
% n& z3 R& E/ c+ {5 S& k& y  oSubject has abnormal blood pressure% z3 p) o; M4 Q2 }- A5 G  [2 @
Subject has abnormal serum creatinine
; q* S" I% ~, f/ k* Z! H* VSubject has evidence of clinically significant proteinuria% E" J6 v+ S) i5 ?
Subject has diabetic ketoacidosis
$ `! {- Y1 ?  [: C+ qSubject is being treated for severe active infection of any type
/ I0 K: u$ V. N! q3 g! J" _$ jA female subject who is breast-feeding, pregnant, or intends to become pregnant during the study+ t0 V3 I+ i; J- {9 [% Y! W/ K
Subject with clinically relevant uncontrolled medical condition not associated with diabetes (e.g. hematologic, renal, hepatic, neurologic, cardiac, or respiratory)4 b; ~5 z# u$ n6 R. ]: ^
Subject is allergic to bovine or porcine products! {* F2 c. e+ `4 {$ C2 `
Subject has evidence of active malignancy, or prior history of active malignancy that has not been in remission for at least 5 years
6 A# S" K. i" ]7 P& S  w8 [ 临床治疗进展：9 i+ h! _' h3 e: C0 C: }
临床实验方案——phase Ⅰ
" Q+ Q( a3 K, t5 b病例数：10-30例
$ B1 @3 K0 U" A$ [" d* R2 S% \% z实验对象：健康人志愿者& |8 ?! `) X6 n' F& i
给药方式：静脉注射，低剂量5 `! b# W' F: N7 C
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临床数据监察与分析：观察人体对于制剂的耐受程度和药代动力学，以及制剂的安全性评价，为制定给药方案提供依据2 h7 [0 X9 C+ b6 e" w& r
安全性评价应包括：静脉滴注的毒性、不良反应、组织异位、感染、死亡等，安全性评价至少持续180天
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临床实验方案——phase Ⅱ# }  F7 ~9 a7 D& W+ \+ v
病例数：＞100例
5 n& y) L4 O, W/ h患者要求：Ⅲ级、Ⅳ级aGVHD患者,或者使用激素类药物三天后无效者，对于重度感染者、器官衰竭不可逆转者、因为实体瘤而接受移植的患者以及过敏者应排除在外3 v1 a: d+ T! p' w6 n# H5 {- s' R' \
给药方式：静脉注射，每周两次，间隔3天，持续4周
, J0 ~! }0 l; Q对照组：双盲实验法，患者被随机分为对照组或者实验组，实验组：对照组=2:1, d4 A5 z: D( z
临床数据监察与分析：检验干细胞治疗方案的有效性，并进一步评价其安全性  M8 J0 {3 J5 @$ K$ f
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临床实验方案——phase Ⅲ
% D! A$ e4 i4 u4 h& u4 I病例数：＞300例
6 a$ _: n9 @& n' t/ k9 q患者要求：Ⅲ级、Ⅳ级aGVHD患者,或者使用激素类药物三天后无效者，对于重度感染者、器官衰竭不可逆转者、因为实体瘤而接受移植的患者以及过敏者应排除在外
4 s6 [$ }) Z4 P$ \2 H给药方式：静脉注射，每周两次，间隔3天，持续4周
1 I% ^2 I; y% m1 }% f对照组：双盲实验法，患者被随机分为对照组或者实验组，实验组：对照组=2:1
9 g3 G5 q9 e! D2 Q. ?End points：28天后症状缓解，180天存活
5 }1 m# E( K& q) U2 I4 I: b临床数据监察与分析：进一步明确干细胞治疗方案的有效性，监测其不良反应，评价其与现行的传统治疗方式比较的优势，治疗后随访，收集更多的信息为其临床应用做准备。
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同样大家可以针对该注射剂谈谈自己的看法，该注射剂为批准的静脉注射剂，对于以后干细胞的静脉注射剂起了很好的指导作用。