Idatha yeSigaba sesi-III malunga neyeza elitsha laseTshayina lesithsaba somlomo kwi-NEJM libonisa ukusebenza ngokungekho ngaphantsi kwePaxlovid

Ngeeyure zokuqala ze-29 kaDisemba, i-NEJM yapapasha kwi-intanethi isifundo esitsha senqanaba lesithathu le-coronavirus yaseTshayina i-VV116.Iziphumo zabonisa ukuba i-VV116 yayingekho mbi kune-Paxlovid (nematovir/ritonavir) ngokobude bexesha lokuchacha kweklinikhi kwaye ibeneziganeko ezimbi ezimbalwa.

Umthombo womfanekiso:NEJM

Ixesha lokubuyisela iMedi kwiintsuku ze-4, izinga lesiganeko esibi 67.4%

I-VV116 lichiza lomlomo le-nucleoside anti-new coronavirus (SARS-CoV-2) ichiza eliphuhliswe ngentsebenziswano noJunsit kunye noWang Shan Wang Shui, kwaye iyi-RdRp inhibitor kunye ne-remdesivir yaseGiliyadi, i-Merck Sharp & ne-Dohme's molnupiravir kunye ne-Real Biologics' azelvudine.

Ngo-2021, ulingo lwezonyango lwesigaba II se-VV116 lwagqitywa e-Uzbekistan.Iziphumo zophando zibonise ukuba iqela le-VV116 linokuphucula ngcono iimpawu zekliniki kwaye linciphise kakhulu umngcipheko wokuqhubela phambili kwifom ebalulekileyo kunye nokufa xa kuthelekiswa neqela lokulawula.Ngokusekwe kwiziphumo ezincumisayo zolu lingo, i-VV116 yamkelwe e-Uzbekistan kunyango lwezigulane ezine-COVID-19 ephakathi ukuya kweyomandundu, kwaye iye yaba lichiza lomlomo elitsha lokuqala elivunyiweyo ukuba lithengiswe phesheya eTshayina [1].

Esi sigaba sesi-III solingo lwezonyango [2] (NCT05341609), ekhokelwa nguProf Zhao Ren weSibhedlele saseShanghai Ruijin, uProf Gaoyuan weSibhedlele saseShanghai Renji kunye no-Academician uNing Guang weSibhedlele saseShanghai Ruijin, sagqitywa ngexesha lokuqhambuka okubangelwa yi-Omicron variant ( B.1.1.529) ukusuka ngoMatshi ukuya kuMeyi eShanghai, ngenjongo yokuvavanya ukusebenza kunye nokhuseleko lwe-VV116 ngokuchasene ne-Paxlovid kunyango lwakwangoko lwezigulane ezinobulali ukuya phakathi kwe-COVID-19.Injongo yayikukuvavanya ukusebenza kunye nokhuseleko lwe-VV116 xa ithelekiswa ne-Paxlovid kunyango lwakwangoko lwezigulane ezine-COVID-19 ephakathi ukuya kweyokuphakathi.

Umthombo womfanekiso: Isalathisi 2

Ulingo olubanzi, olungaboniyo, olungaboniyo, olungenamkhethe, olulawulwa ngabantu abadala abangama-822 abaguli be-Covid-19 abasemngciphekweni omkhulu wokuqhubela phambili kunye neempawu ezithambileyo ukuya kweziphakathi lwenziwa phakathi komhla we-4 ku-Epreli kunye nomhla wesi-2 kuMeyi ka-2022 ukuvavanya ukufaneleka kwabathathi-nxaxheba abavela kwizibhedlele ezisixhenxe eShanghai, eTshayina.Ekugqibeleni, abathathi-nxaxheba abangama-771 bafumana nokuba yi-VV116 (384, 600 mg rhoqo kwiiyure ze-12 ngosuku loku-1 kunye ne-300 mg nganye iiyure ezili-12 ngeentsuku ze-2-5) okanye i-Paxovid (387, 300 mg nimatuvir + 100 mg ritonavir rhoqo kwiiyure ze-12 ngeentsuku ezi-5) iyeza lomlomo.

Iziphumo zolu phononongo lweklinikhi zibonise ukuba unyango lwangethuba nge-VV116 oluphakathi ukuya kwe-COVID-19 ludibene nesiphelo sokuqala (ixesha lokuzinzisa ukuchacha kweklinikhi) eliqikelelweyo yinkqubo yezonyango: ixesha eliphakathi lokuchacha ekliniki yayiziintsuku ezi-4 kwiqela le-VV116 kunye nezi-5. iintsuku kwiqela lePaxlovid (umlinganiselo wengozi, 1.17; 95% CI, 1.02 ukuya kwi-1.36; umda ophantsi. >0.8).

Ukugcina ixesha lokubuyisela iklinikhi

Isiphelo seprayimari nesesekondari (uhlalutyo olubanzi lwabemi)

Umthombo womfanekiso: Isalathisi 2

Ngokokhuseleko, abathathi-nxaxheba abafumana i-VV116 bachaze iziganeko ezimbi ezimbalwa (67.4%) kunabo bafumana i-Paxlovid (77.3%) kwi-28-day-up-upload, kwaye iziganeko zeBanga lesi-3 / 4 ziphantsi kwi-VV116 (2.6%). ) kunePaxlovid (5.7%).

Iziganeko ezimbi (abantu abakhuselekileyo)

Umthombo womfanekiso: Isalathisi 2

Iingxabano kunye nemibuzo

NgoMeyi 23, 2022, uJuniper wadiza ukuba iSigaba sesi-III sofundo lweklinikhi lobhaliso lwe-VV116 ngokuchasene ne-PAXLOVID kunyango lwakwangoko lwe-COVID-19 ephakathi ukuya kwephakathi (NCT05341609) yadibana nesiphelo sayo sokuqala.

Umthombo womfanekiso: Isalathisi 1

Ngexesha apho iinkcukacha zetyala zazingekho, ingxabano ejikeleze isifundo seSigaba sesi-III yayiphindwe kabini: okokuqala, yayiyisifundo esisodwa esingaboniyo kwaye, ngokungabikho kolawulo lwe-placebo, kwakusoyikwa ukuba kuya kuba nzima ukugweba. ichiza ngokupheleleyo;okwesibini, bekukho imibuzo malunga neziphelo zeklinikhi.

Iikhrayitheriya zokubandakanywa kwekliniki zeJuniper zezi (i) iziphumo ezilungileyo zovavanyo olutsha lwesithsaba, (ii) uphawu olunye okanye ngaphezulu oluphakathi okanye oluphakathi lwe-COVID-19, kunye (iii) nezigulana ezisemngciphekweni omkhulu we-COVID-19, kubandakanywa nokufa.Nangona kunjalo, ekuphela kwesiphelo sekliniki 'lixesha lokuzinzisa ukuchacha kweklinikhi'.

Ngaphambi nje kokubhengezwa, ngoMeyi 14, iJuniper yayihlaziywe iziphelo zeklinikhi ngokususa enye yeziphumo eziphambili zeklinikhi, "umlinganiselo wokuguqulwa kwisifo esibi okanye ukufa" [3].

Umthombo womfanekiso: Isalathisi 1

Ezi ngongoma zimbini ziphambili zokuphikisana nazo zaqwalaselwa ngokukodwa kwisifundo esipapashiweyo.

Ngenxa yokuqhambuka kwequbuliso kwe-Omicron, ukuveliswa kweepilisi ze-placebo ze-Paxlovid akuzange kugqitywe ngaphambi kokuqala kovavanyo kwaye ngoko ke abaphandi abazange bakwazi ukuqhuba olu vavanyo ngokusebenzisa i-double-blind-blind-mock design.Ngokubhekiselele kwinkalo eyodwa-imfama yovavanyo lweklinikhi, uJuniper uthe iprotocol yenziwa emva kokunxibelelana nabasemagunyeni kunye nokuba uyilo olulodwa olungaboniyo luthetha ukuba akukho mphenyi (kubandakanywa nomvavanyi wesiphelo sokufunda) okanye umxhasi uya kukwazi. ulwabiwo oluthile lweyeza zonyango de i-database yokugqibela ivaliwe ekupheleni kophononongo.

Ukuza kuthi ga kwixesha lovavanyo lokugqibela, akukho namnye kubathathi-nxaxheba kulingo oye wasweleka okanye ukuqhubela phambili kwisiganeko esiqatha se-Covid-19, ke akukho zigqibo zinokuthathwa malunga nokusebenza kwe-VV116 ekuthinteleni ukuqhubela phambili ukuya kwi-Covid-19 eqatha okanye ebaluleke kakhulu. okanye ukufa.Idatha ibonise ukuba ixesha eliqikelelweyo le-median ukusuka kwi-randomisation ukuya kwi-regression eqhubekayo ye-Covid-19-impawu ezijoliswe kuyo yayiziintsuku ze-7 (95% CI, 7 ukuya kwi-8) kumaqela omabini (umlinganiselo wengozi, 1.06; 95% CI, 0.91 ukuya kwi-1.22) [2].Akukho nzima ukucacisa ukuba kutheni isiphelo esiphambili 'sezinga lokuguqulela kwisigulo esiqatha okanye ukufa', esasetwa ekuqaleni phambi kokuphela kovavanyo, sasuswa.

Ngomhla we-18 kuMeyi ka-2022, ijenali ye-Emerging Microbes & Infections yapapasha iziphumo zolingo lokuqala lwezonyango lwe-VV116 kwizigulana ezosulelwe ngokwahluka kwe-Omicron [4], uphononongo oluvulekileyo, olulindelekileyo lweqela elinezigulana ezili-136 eziqinisekisiweyo.

Idatha evela kuphononongo ibonise ukuba izigulane ezinesifo se-Omicron ezisebenzisa i-VV116 kwiintsuku ze-5 zovavanyo lwabo lokuqala oluhle lwe-nucleic acid zinexesha lokunciphisa i-nucleic acid kwiintsuku ze-8.56, ngaphantsi kweentsuku ze-11.13 kwiqela lolawulo.Ulawulo lwe-VV116 kwizigulane ezinempawu ngaphakathi kwexesha lesi sifundo (i-2-10 iintsuku zovavanyo lokuqala lwe-nucleic acid) zinciphisa ixesha lokunciphisa i-nucleic acid kuzo zonke izigulane.Ngokubhekiselele kukhuseleko lweziyobisi, akukho miphumo emibi kakhulu yabonwa kwiqela le-VV116 lonyango.

Umthombo womfanekiso: Isalathisi 4

Kukho ulingo lwezonyango oluqhubayo oluthathu kwi-VV116, ezibini kuzo zizifundo zesigaba III kwi-COVID-19 ephakathi ukuya kwephakathi (NCT05242042, NCT05582629).Olunye ulingo oluphakathi ukuya koluqatha lwe-COVID-19 liziko lamazwe ngamazwe, elingenamkhethe, elibumfama kabini kwisigaba sesi-III sophononongo lwezonyango (NCT05279235) lokuvavanya ukusebenza nokhuseleko lwe-VV116 xa kuthelekiswa nonyango oluqhelekileyo.Ngokwesaziso sikaJuniper, isigulana sokuqala sabhaliswa kwaye sajoliswa ngoMatshi ka-2022.

Umthombo womfanekiso:clinicaltrials.gov

IiReferensi:

[1] IJunshi Biotech: Isibhengezo ngesiphelo esiphambili seSigaba sesi-III esibhalisiweyo sophononongo lwezonyango lwe-VV116 ngokuchasene ne-PAXLOVID yonyango lwakwangoko lwe-COVID-19

[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 Ai , Yi Zhang, Jianming Zheng, Xiaogang Gao, Junming Xu, Hao 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.