Idatha yeSigaba sesiThathu malunga neyeza elitsha laseTshayina elisebenzisa umqhele womlomo kwi-NEJM ibonisa ukusebenza kakuhle okungekho ngaphantsi kwePaxlovid

Kwiiyure zokuqala zomhla wama-29 kuDisemba, i-NEJM yapapasha kwi-intanethi uphando olutsha lwesigaba sesi-3 seklinikhi ye-VV116 entsha yaseTshayina. Iziphumo zibonise ukuba i-VV116 yayingekho mbi kunePaxlovid (nematovir/ritonavir) ngokwexesha lokuchacha kweklinikhi kwaye yayineziganeko ezimbalwa ezimbi.

Umthombo womfanekiso: NEJM

Ixesha eliphakathi lokuchacha liziintsuku ezi-4, izinga lesiganeko esibi liyi-67.4%

I-VV116 liyeza elilwa ne-coronavirus entsha elivela kwi-nucleoside (SARS-CoV-2) elenziwe ngentsebenziswano ne-Junsit kunye ne-Wang Shan Wang Shui, kwaye liyi-RdRp inhibitor kunye ne-remdesivir yase-Gilead, i-Merck Sharp kunye ne-Dohme's molnupiravir kunye ne-azelvudine yeReal Biologics.

Ngowama-2021, uvavanyo lweklinikhi lwesigaba sesiBini se-VV116 lwagqitywa e-Uzbekistan. Iziphumo zolu phononongo zibonise ukuba iqela le-VV116 lingaziphucula ngcono iimpawu zonyango kwaye linciphise kakhulu umngcipheko wokuqhubela phambili ukuya kwimo ebalulekileyo kunye nokufa xa kuthelekiswa neqela lolawulo. Ngokusekelwe kwiziphumo ezilungileyo zolu vavanyo, i-VV116 ivunyiwe e-Uzbekistan kunyango lwezigulane ezine-COVID-19 ephakathi ukuya kweyona inzima, kwaye ibe liyeza lokuqala elitsha le-coronary elivunyiweyo ukuthengiswa kwamanye amazwe e-China [1].

Olu vavanyo lweklinikhi lwesigaba sesiThathu [2] (NCT05341609), olukhokelwa nguNjingalwazi uZhao Ren weSibhedlele iShanghai Ruijin, uNjingalwazi uGaoyuan weSibhedlele iShanghai Renji kunye noNjingalwazi uNing Guang weSibhedlele iShanghai Ruijin, lugqitywe ngexesha lokuqhambuka okubangelwe yi-Omicron variant (B.1.1.529) ukusuka ngoMatshi ukuya kuMeyi eShanghai, ngenjongo yokuvavanya ukusebenza kakuhle kunye nokhuseleko lwe-VV116 ngokuchasene nePaxlovid kunyango lwangoko lwezigulane ezine-COVID-19 engaphantsi ukuya kwephakathi. Injongo yayikukuvavanya ukusebenza kakuhle kunye nokhuseleko lwe-VV116 ngokuchasene nePaxlovid kunyango lwangoko lwezigulane ezine-COVID-19 engaphantsi ukuya kwephakathi.

Umthombo womfanekiso: Isalathiso sesi-2

Uvavanyo oluqhutywa ngamaziko amaninzi, olungakhange lubonwe ngamehlo, olucwangcisiweyo, nolulawulwayo lwezigulane ezingama-822 zabantu abadala zeCovid-19 ezisengozini enkulu yokuqhubela phambili kwaye ezineempawu ezincinci ukuya kweziphakathi lwenziwe phakathi komhla wesi-4 ku-Epreli nomhla wesi-2 kuMeyi 2022 ukuvavanya ukufaneleka kwabathathi-nxaxheba abavela kwizibhedlele ezisixhenxe eShanghai, eTshayina. Ekugqibeleni, abathathi-nxaxheba abangama-771 bafumene i-VV116 (384, 600 mg qho emva kweeyure ezili-12 ngosuku loku-1 kunye ne-300 mg qho emva kweeyure ezili-12 ngosuku lwesi-2 ukuya kolwesi-5) okanye iPaxovid (387, 300 mg nimatuvir + 100 mg ritonavir qho emva kweeyure ezili-12 kangangeentsuku ezi-5) njengamayeza omlomo.

Iziphumo zolu phononongo lweklinikhi zibonise ukuba unyango lwasekuqaleni nge-VV116 ye-COVID-19 ethambileyo ukuya kwephakathi lufikelele kwinqanaba lokuqala (ixesha lokuchacha okuqhubekayo kweklinikhi) elalixelwe kwangaphambili yinkqubo yeklinikhi: ixesha eliphakathi lokuchacha kweklinikhi yayiziintsuku ezi-4 kwiqela le-VV116 kunye neentsuku ezi-5 kwiqela lePaxlovid (umlinganiselo weengozi, 1.17; 95% CI, 1.02 ukuya kwi-1.36; umda ophantsi. >0.8).

Ukugcina ixesha lokuchacha kweklinikhi

Iziphumo zokuphumelela eziphambili nezesibini (uhlalutyo olupheleleyo lwabemi)

Umthombo womfanekiso: Isalathiso sesi-2

Ngokuphathelele ukhuseleko, abathathi-nxaxheba abafumene i-VV116 baxele ukuba kukho iziganeko ezibi ezimbalwa (67.4%) kunabo bafumana i-Paxlovid (77.3%) kulandelelwano lweentsuku ezingama-28, kwaye iziganeko ezibi zeBanga lesi-3/4 zaziphantsi kwi-VV116 (2.6%) kunakwi-Paxlovid (5.7%).

Iziganeko ezimbi (abantu abakhuselekileyo)

Umthombo womfanekiso: Isalathiso sesi-2

Iimpikiswano nemibuzo

Ngomhla wama-23 kuCanzibe, ngowama-2022, uJuniper watyhila ukuba uphando lweklinikhi lobhaliso lweSigaba sesiThathu lwe-VV116 xa kuthelekiswa ne-PAXLOVID lonyango lwasekuqaleni lwe-COVID-19 ebuthathaka ukuya kwephakathi (NCT05341609) lufikelele kwisiphelo salo sophando oluphambili.

Umthombo womfanekiso: Isalathiso 1

Ngexesha apho iinkcukacha zovavanyo zazingekho, impikiswano ejikeleze uphando lweSigaba sesiThathu yayizimbini: okokuqala, yayiluphononongo olungaboniyo kwaye, xa kungekho lawulo lwe-placebo, kwakusoyikwa ukuba kuya kuba nzima ukugweba ichiza ngokupheleleyo ngendlela echanekileyo; okwesibini, kwakukho imibuzo malunga neziphumo zonyango.

Iikhrayitheriya zokubandakanywa kweJuniper kwiklinikhi zezi (i) iziphumo ezilungileyo zovavanyo olutsha lwe-crown, (ii) uphawu olunye okanye ezingaphezulu ze-COVID-19 eziphantsi okanye eziphakathi, kunye (iii) nezigulana ezisengozini enkulu ye-COVID-19 enzima, kubandakanya nokufa. Nangona kunjalo, ukuphela kwesiphelo seklinikhi 'lixesha lokuqhubeka nokuchacha kweklinikhi'.

Ngaphambi nje kwesi sibhengezo, nge-14 kaMeyi, uJuniper wayehlaziye iziphelo zeklinikhi ngokususa enye yeziphelo eziphambili zeklinikhi, "umlinganiselo wokuguqulwa kube sisifo esibi okanye ukufa" [3].

Umthombo womfanekiso: Isalathiso 1

Ezi ngongoma zimbini ziphambili zempikiswano nazo zijongwe ngokukodwa kuphando olushicilelweyo.

Ngenxa yokuqhambuka ngequbuliso kwe-Omicron, ukuveliswa kweepilisi ze-placebo zePaxlovid bekungekagqitywa ngaphambi kokuqala kovavanyo kwaye ngenxa yoko abaphandi babengenakukwazi ukuqhuba olu vavanyo besebenzisa uyilo olungaboni kabini, olungabonakaliyo. Ngokuphathelele icala elingaboniyo lovavanyo lweklinikhi, uJuniper uthe le nkqubo yenziwe emva kokunxibelelana nabasemagunyeni abalawulayo kwaye uyilo olungabonakaliyo luthetha ukuba umphandi (kuquka umvavanyi wesiphelo sophando) okanye umxhasi akayi kwazi ukwabiwa kwamayeza athile onyango de kube yidathabheyisi yokugqibela itshixiwe ekupheleni kophando.

Kude kube lixesha lohlalutyo lokugqibela, akukho namnye kubathathi-nxaxheba kuvavanyo owayekhe wafa okanye waqhubeka ukuya kwisiganeko esinzima seCovid-19, ngoko ke akukho zigqibo zinokuthathwa malunga nokusebenza kakuhle kwe-VV116 ekuthinteleni ukuqhubela phambili ukuya kwiCovid-19 okanye ukufa okuqatha okanye okubalulekileyo. Idatha ibonise ukuba ixesha eliphakathi eliqikelelweyo ukusuka kwi-randomisation ukuya ekubuyeleni okuqhubekekayo kweempawu ezijolise kwiCovid-19 yayiziintsuku ezisi-7 (95% CI, 7 ukuya ku-8) kumaqela omabini (umlinganiselo wobungozi, 1.06; 95% CI, 0.91 ukuya ku-1.22) [2]. Akunzima ukuchaza ukuba kutheni isiphelo esiphambili 'sezinga lokuguquka ukuya kwisifo okanye ukufa okuqatha', esasimiselwe ngaphambi kokuphela kovavanyo, sasuswa.

Ngomhla we-18 kuCanzibe 2022, ijenali i-Emerging Microbes & Infections yapapasha iziphumo zovavanyo lokuqala lweklinikhi lwe-VV116 kwizigulana ezine-Omicron variant [4], uphando oluvulekileyo nolunokwenzeka lweqela elinezigulane ezili-136 eziqinisekisiweyo ukuba zingeniswe.

Idatha evela kuphononongo ibonise ukuba izigulane ezine-Omicron sulelo ezisebenzise i-VV116 kwiintsuku ezi-5 emva kovavanyo lwazo lokuqala lwe-nucleic acid zinexesha lokubuyela umva kwe-nucleic acid kwiintsuku ezi-8.56, ngaphantsi kweentsuku ezili-11.13 kwiqela lolawulo. Ukunikezelwa kwe-VV116 kwizigulane ezineempawu ngexesha lophando (iintsuku ezi-2-10 zovavanyo lokuqala lwe-nucleic acid) kunciphisa ixesha lokubuyela umva kwe-nucleic acid kuzo zonke izigulane. Ngokuphathelele ukhuseleko lwamayeza, akukho miphumo mibi ibonakalayo kwiqela lonyango lwe-VV116.

Umthombo womfanekiso: Isalathiso 4

Kukho iimvavanyo ezintathu eziqhubekayo zeklinikhi kwi-VV116, ezimbini kuzo zizifundo zesigaba sesithathu kwi-COVID-19 ethambileyo ukuya kwephakathi (NCT05242042, NCT05582629). Olunye uvavanyo lwe-COVID-19 ephakathi ukuya kweyona inzima luphononongo lweklinikhi lwesigaba sesithathu oluqhutywa ngamaziko amaninzi, olucwangcisiweyo, olungaboni kabini (NCT05279235) lokuvavanya ukusebenza kakuhle kunye nokhuseleko lwe-VV116 xa kuthelekiswa nonyango oluqhelekileyo. Ngokwesibhengezo sikaJuniper, isigulana sokuqala sabhaliswa saza sanikwa idosi ngoMatshi 2022.

Umthombo womfanekiso: clinicaltrials.gov

Iireferensi:

[1]Junshi Biotech: Isaziso malunga nesiphelo esiphambili seSigaba sesiThathu sophando lweklinikhi olubhalisiweyo lwe-VV116 ngokuchasene ne-PAXLOVID ukuze kufumaneke unyango lwangoko lwe-COVID-19 ebuthathaka ukuya kwephakathi.

[2]https://www.nejm.org/doi/full/10.1056/NEJMoa2208822?query=featured_home[3]https://clinicaltrials.gov/ct2/show/record/NCT05341609[4] Ensi Ma, Jingwen Aiming Yi Zhang, Jingwen Aiming Yi Zhang, Juming Xheng Xiao Yin, Zhiren Fu, Hao Xing, Li Li, Liying Sun, Heyu Huang, Quanbao Zhang, Linlin Xu, Yanting Jin, Rui Chen, Guoyue Lv, Zhijun Zhu, Wenhong Zhang, Zhengxin Wang. (2022) Iprofayili yosulelo lwe-Omicron kunye nesimo sokugonywa phakathi kwe-1881 abamkeli besibindi sokufakelwa kwesibindi: i-multi-centre retrospective cohort. Emerging Microbes & Infections 11:1, amaphepha 2636-2644.