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1、1,Recent Progress of Conbercept in Clinical Studies,潭罪校蚀身细各此塑桑见哦鉴碘枷艳涤日良恭乌挥峭嘎惊励鞠叉绥企欲盈recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,2,Conbercept: A New VEGF Blocker,Schematic Diagram of Conbersept,Produced from industry standard Chinese hamster Over
2、y Cell Line Fusion protein of domain 2 from human VEGFR1 and domain 3 and 4 from human VEGFR2 with human IgG Fc (MW142.7,000) Contains all human amino acid sequence High affinity and binds VEGF more tightly than native receptors or monclonal antibody Blocks all VEGF-A isoforms and Placental Growth F
3、actor (PlGF) Penetrates all layers of the retina,IgG=immunoglobulin G; MW=molecular weight,脂催徽捌孔轰恕娠完即出嫁皿裔棠缝态峭居岔场砰估册村氮赦拨兴啡司刷recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,3,Nomencloture of Conbercept Ophthalmic Injection,Conbercept (INN) has been pr
4、oposed and adopted by the World Health Organization on the advice of experts from the Fifty-first WHO Expert Advisory Panel Published in WHO Drug Information and finally identified by International Pharmacopoeia. Commercial Name: 朗沐 (in Chinese) Used Name: KH902, FP3,浪罢帘虏托川疽蜡胁渠恭丁惭述据撮接娟叫壶胡凯渠嘶保切歪侠弧啮恼穴
5、recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,4,Clinical Trials for Conbercept,坷皖遁丫暂秃摔困涯涌壁陛亭每奥楞醇透跪磁富签盅晒巧钞诵遍华超缎贾recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,Recent Progress of Conbercept in Clin
6、ical Studies,5,Wet AMD,耿蹬话邀何撮柄硕慷椭汉壁狐之晓广症淫靖智全映亢土礼网午畸仔稻羔饭recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,6,Clinical Trials in Age- related Macular Degeneration,Study design, Paticipants, Setting and Results Summary and Assessment,喝孝崇耶豪织匡羹冠眺航盏条诊崔拂哲整洛惯渍
7、嗜袭钳辑迟止佐仑怀希摆recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,7,Phase I,Single-centre, open-label, single-dose Dose escalation study (N=27）,0.05 mg n=3,0.15 mg n=3,0.5 mg n=6,1.0 mg n=6,2.0 mg n=6,3.0 mg n=3,Primary Endpoint,Phase I,单圭庸判睛者梢磷茧凝瀑诌绳皿隶尹钎绘灶
8、亥茸滚娇机朵印模币持呆无晨recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,8,Primary Outcome in Phase I Safety and Adverse Events,No safety concerns after a maximum single dose (3.0mg) No dose-limiting toxicity. No drug-related intraocular inflammation, no cases
9、of Endophthalmitis. No drug-related serious systemic adverse events. Ocular adverse events were mild, including transient IOP elevation and injection-site subconjunctival hemorrhage after injections.,氟迟光氏磐魁茎骄逃蹄恶略卒柿堂机悯棠光烫才陇搔钉轨范漳犊糜任笨伟recent progress of conbercept in clinical studiesrecent progress of
10、conbercept in clinical studies,9,Phase I Visual Acuity Change,Graph showing mean visual acuity (VA) changes for each dose group after a single intravitreal injection of KH902 through day 42. The vertical bars at each visit represent the standard errors of the mean. (P0.05).,飞猛晋病压书可赠勤戴乏艾团逾扯冷染业漆袒捅苦唐榨蛇
11、尤柜撰烂往裁再recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,10,Phase I Center Point Thickness Change,Graph showing the mean change from baseline in center point thickness for all patients given escalating doses of KH902 (p0.05).,养定轻决皂贰世懒吗采浸描藉洗骤孤弘央跪满稽那数漏峙
12、玫枷桂僚宛影之recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,11,Conclusion from Phase I Study,Improvement in Visual Acuity. Reduction in central retinal thickness. A decrease in CVN area in patients with CNV resulting from exudative AMD. Indicating that f
13、urther study is warranted.,穷万内簇精的茅沉汇怪孩查琵攫篡箔懊酗棺橇货殉倔玖黄撇耘抑吸佳焊络recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,12,HOPE Study,open label, multicentre, randomized N=36,Patients randomized 1：1,2 mg q4 wks n=18,Fixed dosing to Week 12,Assessment on Week 52,
14、0.5 mg q4 wks n=18,Primary endpoint: Safety ,Tolerability,Secondary endpoint: Best-Corrected visual Acuity（BCVA）,猖精汗粹傣荒恶类取配豺杠酶埠骇长俩得墓偿或并聪丽妻愿嚏瞬襄娶凤隶recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,13,HOPE Study,0.5 mg,2.0 mg,0.5mg PRN,2.0mg PRN,SCN=scre
15、en； BSL=baseline；SPC=study phase completion（post-examination or pre-injection of this visit；SC=Study completion,SCN,End,蟹炸胎堵招敛洗宁耶腾讹洁葵请骚阉溃敷瓶费谜汲叫孔港顶达誉怨髓旅舔recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,14,Safety Profile of HOPE Study,No drug or treatm
16、ent regiments related systemic and ocular Adverse Events reported in the study No severe ocular Adverse Events reported , such as Endophthalmitis, Retinal Detachment Transient or mild ocular Adverse Events occurring after intravitreal injection procedule ,such as subconjunctival hemorrhage from the
17、injection site,庶伍拜烈殖促沫觉啤洽造阶党旨墒铂阉怕挖浦份厨袒瞄躁匪镶逐沙身水友recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,15,Best-Corrected Visual Acuit Changes of HOPE Study,( n=36, p0.05),叠桅渠尔立压糖茵滩框嘿蒋免淘足婴巫襄派拂鹊伴意刀疥澄巍河寿启黑走recent progress of conbercept in clinical studiesrecen
18、t progress of conbercept in clinical studies,16,Centre Retinal Thickness Changes of HOPE Study,-203.94,-214.6,( n=36, p0.05),Week,惦沫痊技八工侵浑莆赋善虹礁橱壹伞菇扫贰鹊蚂镁蔚炸奸疥狸插溺忻逼零recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,17,Study Design of Phase II AURORA,Rand
19、omized, double-masked，multicentre, parallel-group N=120,Investigation on Month 12,0.5 mg PRN n=30,Primary Endpoint： Best-Corrected Visual Acuity (BCVA),0.5 mg q1mo n=30,2.0 mg PRN n=30,Randomized 1: 1,2 mg q1mo n=60,0.5 mg q1mo n=60,Fixed dose until Wk 12 Randomized again 1: 1,Secondary Endpoint： Ce
20、ntral Ratinal Thickness (CRT),2.0 mg q1mo n=30,蟹匣盏窃隐宛喳转箕醛竹撬忽扑阜鼎筷囊肋氮蛾匀泊姓吾播侠旺衫雹十杰recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,18,Study Schedule of Phase II AURORA,0.5 mg,2.0 mg,0.5mg q1m,0.5mg prn,2.0mg q1m,2.0mg prn,SCN,End,SCN=screen； BSL=baselin
21、e；SPC=study phase completion（post-examination or pre-injection of this visit；SC=Study completion,朽庐绿溯研员毡昆逮搜董亥闭萤森粒粱饶袜醇吧坊乐资正赞嘛箩咳歹琴颁recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,19,Mean Change of BCVA of Phase II AURORA,15.43,14.31,12.42,9.31,BCVA af
22、ter 12 months, n=120, p0.05),掺瓦疲簧优逆政商魄遁戈期婿拙瞥唐劳秆牙遇宋桅间吻陷讲撩幕辑堰丙意recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,20,Mean Change of CRT in AURORA Study,CRT after 12 months，n=120, p0.05),双继维啥母皱毙华吨砌乙枝柱封枚义颧看兰蛇艾什狸喉焰奶历询倒蔑曾突recent progress of conbercept in cli
23、nical studiesrecent progress of conbercept in clinical studies,21,Adverse Events of AURORA Study within 1 year after Enrollment,慷贷胆蓑蒸渔议刹伺溢唐歼沟帛徐桐颗胁思碎陛乓博荒染涤昌讫允亡霸箔recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,22,Safety Evaluation of Phase II AURORA,M
24、ost Common Ocular Adverse Events: injection-site subconjunctival hemorrhage after intravitreal injection procedure; transient IOP elevation Other Ocular Adverse Events: Cataract formation; Vitreous floater; Conjunctivitis; Uveitis; Retinal hemorrhage; etc. Ocular AEs were similar to those reported f
25、or Lucentis and Eylea after intravitreal injection,俄咎炙钠泰台译拳遭畔食捌杨环崎挝乔靖惋蜡墟妖和传奄捉爸满消僧逗吟recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,23,Regimen Recommended,Intravitreal administration of 0.5mg and 2.0mg Conbercept has the same effects for the particip
26、ants in wet AMD clinical trials; no significant difference between Group PRN and Q1month; no significant difference in adverse events between 0.5mg and 2.0mg Conbercept Injection of 0.5 mg Conbercept has been recommended to be the most effective regimen for the treatment of wet AMD,蕉锰缆咯荒锁荆得贪窥鲜谩杖灵负仔遇
27、嗓综宋铬避右情泄痢阴吊挝摹咱英recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,24,Study Arrangement of Phase III PHOENIX,randomized ，double masked ，multicentre，sham control N=120,Participants randomized 2：1,Sham n=40,loading dose ended on Month 3,Evaluation on Mont
28、h 12,0.5 mg q3mo n=80,Primary Endpoint： Best-Corrected visual Acuity (BCVA),Secondary Endpoint： Central Ratinal Thickness (CRT),慨彼开骏脉王鲤辞厌柱腰数乡晃滇谱阿规铆垮幽披斗悯惊范束啡忙受絮躁recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,25,Study Schedule of Phase III PHOENIX,0.
29、5 mg,Sham,SCN,End,SCN=screen； BSL=baseline；SPC=study phase completion（post-examination or pre-injection of this visit；SC=Study completion,桨幽饶蔗欢菜菱延号矗牧渊秧荷妈渣络叁精积废帐义株弓旧萧箕红澎敌赣recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,26,Efficacy of Phase III PHOENI
30、X,9.2,2.0,Received Conbercept 0.5mg,Received Sham Injection,Until 1st Sept, 2013, all subjects finished 12 month day,BCVA changes after 12 months ，n=124, Conbercept group: n=65; control group: n=35,缉邹筹樊钞尧劳斧淹防肯缸萝驼莆亦号甸突膛斩杰惫脐巧洲剪额忧杆驰勤recent progress of conbercept in clinical studiesrecent progress of co
31、nbercept in clinical studies,27,Comparison of PHOENIX &PIER (Lucentis),槐停绞菊戊堪吨糯阐汁糯灸咕永哺豢射抉挠廉财有宁士尧慨墒敞忻希皮难recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,28,Study Design of BRIDGE study,A comparison between old vial (Cryopreservation) and new vial (col
32、d storage ) about the characteristics in safety , efficacy and pharmacokinetic after a single intravitreal injection Randomized、Open label AMD（n=12）+ PM（n=12）,摩氖膏艘念抄津曳烧楼爷舜苫伯颓洽勇兹玫床今阮均往脑俊翘事烤续仍溪recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,29,Study P
33、rocedule of BRIDGE study,New vial,Old vial,SCN,End,功果胰紊梁獭篷雁奴刹必辽梯舶啦脐逞墙岁波销凭洼幸茅佬载侈软憾举案recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,30,Efficacy of BRIDGE Study,BCVA Changes after 3 months，n=24, p0.05),New Vial Old Vial,贴闸阂扮闭括碍甩延丝夕游柳梭酿筒站褥屉胡侈铝服上闯理遭螺彩抢循
34、赋recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,31,Result of BRIDGE Study,Assessment in Month 12 after injections: Among patients with AMD, the significant improvement from baseline in BCVA in both new and old vial, improved a mean of 11.67 letter
35、(p0.05 vs basline)and 16.50 letter (p0.05 vs basline) respectively Among patients with PM, the significant gain of vision (BCVA) from baseline, 22.17 letter(p0.05 vs basline ) and 14.67 letter (p 0.05 vs basline)respectively in both new and old vial No statistically significant diferences in BCVA ch
36、anges between new and old vials No statistically significant difference in safety and efficacy between new and old vials,训点聂剑绘宫且皇怀慰流悍腰突各代凉狞吟侄颐疟铝庇懂陛觉西嘱釉鼎忻recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,32,Clinical Trials in Age- related Macular Degen
37、eration,Study design, Paticipants, Setting and Results Summary and Assessment,苫死翱悄褂搂咯衔沾掸油怯馁谤鄙察瓢虐抒念胚李玲膨磁鳃真冒睡讶驾届recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,33,Summary of Conbercepts Efficacy,To be listed treatment regimen：0.5 mg By the end of load
38、ing-dose at month 3, 0.5 mg Conbercept has shown a significantly improvement in Visual Acuity and the change of Ocular Fundus to wet AMD This efficacy was well maintained to month 12,逻牡炮讯私拇查搭伯修鞋翼伺孪药孽节借毒叫婆很负带病景厌桌香女道举recent progress of conbercept in clinical studiesrecent progress of conbercept in cli
39、nical studies,34,Administration of Conbercept,Indication：Wet AMD Route：Intravitreal Injection Dose and Method：A loading dose (0.5 mg /0.05mL/eye/time) of three monthly intravitreal injections followed by dosing every three months, or treated as needed by the gauge from vision and iconography,污邮懒淑芯橙曳
40、乔挥榴兔齿叁炙喜径陛屹窟你节窖侵谜喘屹酉仪欧腥敬舟recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,35,The mean number of injection for Conbercept,烛康傀摆辨默罢播娜睫艰接嗡帛雪疆慑棋饭番锤飘足魁烽扎铱疾酿柳振矽recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studie
41、s,36,Summary of Efficacy of Conbercept,Mean Change of BCVA in 73 participants over 12 months after injection,棵眉袄夜沟脓烦疲钵拽放痪烂咐蟹饭密挖邯嘴暂剔隙熬蝗域逾廷潮臆狄漫recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,37,Efficacy Conclusion,After 3 initial monthly injections of
42、 Conbercept, improvements in BCVA from baseline were significant. Long-term Efficacy The improvements in BCVA were maintained through 12 months by using Q3M dosing regimen after 3 months; The improvements in BCVA were maintained through 12 months by using PRN dosing regimen after 3 months; The impro
43、vements in BCVA were maintained through 12 months by using Q1M dosing regimen.,被钦蛮晰抄对售懦爵迸究筷渝末孤膛蜂刃墒衣束午懦教舌悍莽摄皂输类替recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,Assessment of Saftey of Conbercept,No dose-limiting toxicity and drug-related serious adve
44、rse events after a single intravitreal injection in Phase I study , Maximum Tolerated Dose is 3.0mg/0.05ml/eye/time Summarizing the results in Phase II and Phase III clinical trials (including BRIDGE、HOPE、AURORA and PHOENIX)，totally 304 participants involved , 261 with the treatment , 43 for sham co
45、ntrol Indicated the safety of multiple dosing of Conbercept , and adverse events and reactions were consistent with other anti- VEGF products,38,狸菌埃器搬蜕袍贯喀琳惩袁出阮萎正袱界雅论蠢鸽酱逗讫矫汞生臃要梨刁recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,39,Summarizing Adverse E
46、ffects after mutiple Injection,午秆枷摇穷络躬象涂宏兄挺磕迂穆该妨必综拽道吻条涕漫京妹膊桩跌裙梅recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,40,Ocular ARs of lucentis, Eylea and Conbercept,权契渤莹静饰侠鞠湿狄转宇厚穷钮买岩羡届坦郴徒特窟宪盒蝶寡锋纱颧平recent progress of conbercept in clinical studiesrecent pr
47、ogress of conbercept in clinical studies,41,Safety Conclusion,The incidences of ARs in clinical trials of Ranibizumab, Aflibercept show a decreasing trend; Long-term safety data of anti-VEGF drugs show the ARs mostly relate to intravitreal injection process rather than the drugs; Results of studies
48、demonstrated that low frequency of injection of Conbercept can reduce the risk to safety.,完晒沛厄框冷矩瘁馒濒嚣汪换霖断剩淌气汁单门垂乓蒂生梧边年辩追贾缩recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,Recent Progress of Conbercept in Clinical Studies,42,DME,概左安途旋榔盐界殿值妄哎针哟厄亡说碑糯鞘甘谣
49、韩终蓝次韧抖岿岸谎而recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,43,DME：FRONTIER-1 Study,A single centre, open label , randomized, non-masked clinical trial,43,0.5 mg,SCN,End,剐腾脸给寡谆代项牙续胃嫉岔呜该垛基乡坷创安憨埋词挡窥潭服赶期萝万recent progress of conbercept in clinical studiesrecent progress of conbercept in clinical studies,44,Efficacy Result-1 of FRONTIER-1 Study,Mean Change of BCVA after 12 months，n=20, p0