Idatha yeSigaba III ngomuthi omusha womqhele womlomo waseChina ku-NEJM ikhombisa ukusebenza kahle okungengaphansi kwe-Paxlovid

Ekuqaleni kwangomhla zingama-29 kuZibandlela, i-NEJM ishicilele ku-inthanethi ucwaningo olusha lwesigaba sesi-III se-coronavirus entsha yaseChina i-VV116. Imiphumela yabonisa ukuthi i-VV116 yayingeyimbi kakhulu kune-Paxlovid (nematovir/ritonavir) ngokwesikhathi sokululama emtholampilo futhi ibe nezigameko ezimbi ezimbalwa.

Umthombo wesithombe:NEJM

Isikhathi sokutakula esimaphakathi izinsuku ezi-4, izinga lomcimbi omubi ngu-67.4%

I-VV116 iyisidakamizwa somlomo se-nucleoside anti-new coronavirus (SARS-CoV-2) esakhiwe ngokubambisana no-Junsit no-Wang Shan Wang Shui, futhi iyisivimbeli se-RdRp kanye ne-remdesivir yase-Gilead, i-Merck Sharp & Dohme's molnupiravir kanye ne-azelvudine ye-Real Biologics.

Ngo-2021, ukuhlolwa komtholampilo kwesigaba II se-VV116 kwaqedwa e-Uzbekistan. Imiphumela yocwaningo ibonise ukuthi iqembu le-VV116 lingakwazi ukuthuthukisa kangcono izimpawu zomtholampilo futhi linciphise kakhulu ingozi yokuqhubekela phambili kwifomu elibucayi nokufa uma kuqhathaniswa neqembu lokulawula. Ngokusekelwe emiphumeleni emihle yalolu cwaningo, i-VV116 igunyazwe e-Uzbekistan ukuze zelashwe iziguli ezine-COVID-19 emaphakathi ukuya kobucayi, futhi isibe umuthi wokuqala womlomo omusha ovunyelwe ukumakethwa phesheya kwezilwandle eChina [1].

Lesi sigaba sesi-III sesilingo somtholampilo[2] (NCT05341609), esiholwa nguProf. Zhao Ren weSibhedlela sase-Shanghai Ruijin, uProf. Gaoyuan wase-Shanghai Renji Hospital kanye no-Academician Ning Guang wase-Shanghai Ruijin Hospital, saqedwa phakathi nokuqubuka okubangelwa ukwahluka kwe-Omicron (B.1.1.529) kusukela ngoMashi kuya e-Shanghai kusukela ngoMashi kuya ku-May 29 ye-VV116 iqhathaniswa ne-Paxlovid yokwelashwa kusenesikhathi kweziguli ezine-COVID-19 ethambile kuya kwemaphakathi. Inhloso bekuwukuhlola ukusebenza kahle nokuphepha kwe-VV116 uma iqhathaniswa ne-Paxlovid yokwelashwa kusenesikhathi kweziguli ezine-COVID-19 emaphakathi kuya kokulinganisela.

Umthombo wesithombe: Inkomba 2

Isivivinyo se-multicentre, esingaboni, esingaboni, esingahleliwe, esilawulwayo seziguli ezikhulile ezingama-822 ze-Covid-19 ezisengcupheni enkulu yokuqhubekela phambili futhi ezinezimpawu ezithambile nezilinganiselayo zenziwa phakathi komhlaka 4 Ephreli no-2 Meyi 2022 ukuze kuhlolwe ukufaneleka kwabahlanganyeli abavela ezibhedlela eziyisikhombisa eShanghai, eChina. Ekugcineni, ababambiqhaza abangama-771 bathola noma i-VV116 (384, 600 mg njalo emahoreni ayi-12 ngosuku loku-1 no-300 mg njalo emahoreni ayi-12 ezinsukwini ezi-2-5) noma i-Paxovid (387, 300 mg nimatuvir + 100 mg ritonavir njalo emahoreni ayi-12 njengemithi yomlomo izinsuku ezinhlanu).

Imiphumela yalolu cwaningo lomtholampilo ikhombise ukuthi ukwelashwa kusenesikhathi nge-VV116 kwe-COVID-19 ethambile kuye kwalinganisela kwahlangabezana nesiphetho sokuqala (isikhathi sokululama emtholampilo) esibikezelwe umthetho olandelwayo womtholampilo: isikhathi esimaphakathi sokululama emtholampilo kwakuyizinsuku ezi-4 eqenjini le-VV116 kanye nezinsuku ezi-5 eqenjini le-Paxlovid (isilinganiso sengozi, 1.17; 95% CI kuya ku-1.32% sehlise umkhawulo, 1.02).

Ukugcina isikhathi sokululama emtholampilo

Iziphetho zokusebenza ngempumelelo okuyisisekelo nesesibili (ukuhlaziywa okuphelele kwesibalo sabantu)

Umthombo wesithombe: Inkomba 2

Mayelana nokuphepha, abahlanganyeli abathola i-VV116 babike izehlakalo ezimbi ezimbalwa (67.4%) kunalabo abathola i-Paxlovid (77.3%) ekulandeleni kwezinsuku ezingu-28, futhi izehlakalo zeBanga lesi-3 / 4 zezenzakalo ezimbi zaziphansi ku-VV116 (2.6%) kune-Paxlovid (5.7%).

Izehlakalo ezimbi (abantu abaphephile)

Umthombo wesithombe: Inkomba 2

Izingxabano nemibuzo

Ngomhla zingama-23 kuNhlaba, 2022, uJuniper wadalula ukuthi isifundo somtholampilo sokubhaliswa kweSigaba III se-VV116 iqhathaniswa ne-PAXLOVID yokwelashwa kwangaphambi kwesikhathi kwe-COVID-19 ethambile kuya kwemaphakathi (NCT05341609) ihlangabezane nesiphetho sayo sokuqala.

Umthombo wesithombe: Inkomba 1

Ngesikhathi lapho imininingwane yokuqulwa kwecala ingekho, impikiswano ezungeze isifundo seSigaba sesi-III yayikabili: okokuqala, kwakuwucwaningo olulodwa oluyimpumputhe futhi, lapho kungabikho ukulawulwa kwe-placebo, kwakusaba ukuthi kuyoba nzima ukwahlulela izidakamizwa ngokuphelele; okwesibili, bekunemibuzo mayelana neziphetho zomtholampilo.

Inqubo yokufakwa emtholampilo yeJuniper (i) imiphumela emihle yokuhlolwa komqhele omusha, (ii) uphawu olulodwa noma ngaphezulu oluthambile noma olumaphakathi lwe-COVID-19, kanye (iii) neziguli ezisengozini enkulu ye-COVID-19 enzima, okuhlanganisa nokufa. Kodwa-ke, ukuphela kwesiphetho somtholampilo 'isikhathi sokusimama komtholampilo'.

Ngaphambi nje kwesimemezelo, ngoMeyi 14, uJuniper wayebuyekeze iziphetho zomtholampilo ngokususa enye yezindawo eziyinhloko zomtholampilo, "ingxenye yokuguqulwa kokugula okubi noma ukufa" [3].

Umthombo wesithombe: Inkomba 1

Lawa maphuzu amabili asemqoka engxabano nawo adingidwa ngqo ocwaningweni olushicilelwe.

Ngenxa yokuqubuka kungazelelwe kwe-Omicron, ukukhiqizwa kwamaphilisi e-placebo e-Paxlovid kwakungakaqedwa ngaphambi kokuqala kwecala ngakho-ke abaphenyi abakwazanga ukuqhuba lolu cwaningo besebenzisa idizayini eyimpumputhe kabili, eyimbumbulu kabili. Ngokuqondene nesici esisodwa esiyimpumputhe esivivinyweni somtholampilo, uJuniper uthe i-protocol yenziwa ngemva kokuxhumana neziphathimandla ezilawulayo nokuthi umklamo owodwa oyimpumputhe usho ukuthi umphenyi (kuhlanganise nomhloli wokuphela kocwaningo) noma umxhasi uzokwazi ukunikezwa kwemithi ethile yokwelapha kuze kube yilapho i-database yokugcina ivaliwe ekupheleni kocwaningo.

Kuze kube yisikhathi sokuhlaziywa kokugcina, abekho ababambiqhaza ochungechungeni abake bafa noma baqhubekela phambili esenzakalweni esinzima se-Covid-19, ngakho-ke azikho iziphetho ezingafinyelelwa mayelana nokusebenza kwe-VV116 ekuvimbeleni ukuqhubekela phambili ku-Covid-19 enzima noma ebucayi noma ukufa. Idatha ibonise ukuthi isikhathi esilinganiselwe se-median kusukela ekushintsheni okungahleliwe kuya ekuhlehleni okuqhubekayo kwezimpawu ezihlosiwe ezihlobene ne-Covid-19 kwakuyizinsuku ezingu-7 (95% CI, 7 kuya ku-8) kuwo womabili amaqembu (isilinganiso sengozi, 1.06; 95% CI, 0.91 kuya ku-1.22) [2]. Akunzima ukuchaza ukuthi kungani isiphetho esiyinhloko 'sezinga lokuguqulela ekuguleni okubi kakhulu noma ukufa', esasethwa ekuqaleni ngaphambi kokuphela kwecala, sasuswa.

Ngomhla ziyi-18 kuNhlaba wezi-2022, iphephabhuku i-Emerging Microbes & Infections yashicilela imiphumela yokuhlolwa kokuqala komtholampilo kwe-VV116 ezigulini ezitheleleke nge-Omicron variant [4], ucwaningo oluvulekile, olulindelekile lweqembu elineziguli ezingu-136 eziqinisekisiwe.

Idatha evela ocwaningweni ibonise ukuthi iziguli ezinokutheleleka kwe-Omicron ezisebenzisa i-VV116 phakathi kwezinsuku ezingu-5 zokuhlolwa kwazo kokuqala okuhle kwe-nucleic acid zinesikhathi sokuhlehla kwe-nucleic acid yezinsuku ezingu-8.56, ngaphansi kwezinsuku ezingu-11.13 eqenjini lokulawula. Ukuphathwa kwe-VV116 ezigulini ezinezimpawu ngaphakathi kwesikhathi salolu cwaningo (izinsuku ezingu-2-10 zokuhlolwa kokuqala kwe-nucleic acid) kunciphisa isikhathi sokuhlehla kwe-nucleic acid kuzo zonke iziguli. Mayelana nokuphepha kwezidakamizwa, akukho miphumela emibi kakhulu ebonwe eqenjini lokwelapha le-VV116.

Umthombo wesithombe: Inkomba 4

Kunezivivinyo ezintathu eziqhubekayo zomtholampilo ku-VV116, ezimbili zazo okuyizifundo zesigaba III ku-COVID-19 emaphakathi ukuya kwephakathi (NCT05242042, NCT05582629). Olunye uvivinyo lwe-COVID-19 emaphakathi kuya kolunzima luwucwaningo lomtholampilo lwe-multicentre international, randomised, double blind-blind phase III (NCT05279235) lokuhlola ukusebenza kahle nokuphepha kwe-VV116 uma kuqhathaniswa nokwelashwa okujwayelekile. Ngokwesimemezelo sikaJuniper, isiguli sokuqala sabhaliswa futhi sanikezwa umthamo ngoMashi 2022.

Umthombo wesithombe:clinicaltrials.gov

Izithenjwa:

[1]I-Junshi Biotech: Isimemezelo endaweni eyinhloko yocwaningo lomtholampilo olubhalisiwe lweSigaba III se-VV116 uma iqhathaniswa ne-PAXLOVID yokwelashwa kwangaphambi kwesikhathi kwe-COVID-19 emaphakathi kuya kokumaphakathi.

[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 Gau Zheng, Juming Xiao Zhang 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) Iphrofayili yokutheleleka kwe-Omicron kanye nesimo sokugoma phakathi kwabamukeli bokufakelwa kwesibindi abangu-1881: iqoqo le-multi-centre retrospective. I-Emerging Microbes & Infections 11:1, amakhasi 2636-2644.