Cov ntaub ntawv theem III ntawm Tuam Tshoj cov tshuaj tshiab hauv NEJM qhia tau tias qhov ua tau zoo tsis qis dua Paxlovid

Thaum ntxov ntawm lub Kaum Ob Hlis 29, NEJM tau tshaj tawm online txog kev tshawb fawb theem III tshiab ntawm tus kab mob coronavirus Suav tshiab VV116. Cov txiaj ntsig tau qhia tias VV116 tsis phem dua li Paxlovid (nematovir/ritonavir) hais txog lub sijhawm rov zoo thiab muaj tsawg dua cov teeb meem tshwm sim.

Duab los ntawm: NEJM

Lub sijhawm rov zoo nruab nrab yog 4 hnub, tus nqi tshwm sim tsis zoo yog 67.4%

VV116 yog ib qho tshuaj nucleoside tiv thaiv kab mob coronavirus tshiab (SARS-CoV-2) uas tau tsim los ntawm kev koom tes nrog Junsit thiab Wang Shan Wang Shui, thiab yog ib qho tshuaj RdRp inhibitor ua ke nrog Gilead's remdesivir, Merck Sharp & Dohme's molnupiravir thiab Real Biologics' azelvudine.

Xyoo 2021, kev sim tshuaj theem ob ntawm VV116 tau ua tiav hauv Uzbekistan. Cov txiaj ntsig ntawm txoj kev tshawb fawb qhia tau hais tias pawg VV116 tuaj yeem txhim kho cov tsos mob hauv kev kho mob zoo dua thiab txo qhov kev pheej hmoo ntawm kev nce mus rau daim ntawv tseem ceeb thiab kev tuag piv rau pawg tswj. Raws li cov txiaj ntsig zoo ntawm kev sim no, VV116 tau pom zoo hauv Uzbekistan rau kev kho mob rau cov neeg mob uas muaj COVID-19 nruab nrab mus rau hnyav, thiab tau dhau los ua thawj cov tshuaj tshiab hauv qhov ncauj uas tau pom zoo rau kev lag luam txawv teb chaws hauv Suav teb [1].

Qhov kev sim tshuaj theem III no [2] (NCT05341609), coj los ntawm Xibfwb Zhao Ren ntawm Tsev Kho Mob Shanghai Ruijin, Xibfwb Gaoyuan ntawm Tsev Kho Mob Shanghai Renji thiab Tus Kws Qhia Ntawv Ning Guang ntawm Tsev Kho Mob Shanghai Ruijin, tau ua tiav thaum muaj kev sib kis los ntawm Omicron variant (B.1.1.529) txij lub Peb Hlis mus txog lub Tsib Hlis hauv Shanghai, nrog lub hom phiaj ntawm kev ntsuam xyuas qhov ua tau zoo thiab kev nyab xeeb ntawm VV116 piv rau Paxlovid rau kev kho mob thaum ntxov ntawm cov neeg mob uas muaj COVID-19 me me mus rau nruab nrab. Lub hom phiaj yog los ntsuam xyuas qhov ua tau zoo thiab kev nyab xeeb ntawm VV116 piv rau Paxlovid rau kev kho mob thaum ntxov ntawm cov neeg mob uas muaj COVID-19 me me mus rau nruab nrab.

Duab los ntawm: Siv 2

Ib qho kev sim ntau lub chaw, uas tsis tau saib xyuas, tsis raug xaiv, thiab tswj hwm los ntawm cov neeg saib xyuas ntawm 822 tus neeg mob Covid-19 laus uas muaj feem yuav mob hnyav dua thiab muaj cov tsos mob me me mus rau nruab nrab tau ua ntawm 4 Lub Plaub Hlis thiab 2 Tsib Hlis 2022 los ntsuas qhov tsim nyog ntawm cov neeg koom nrog los ntawm xya lub tsev kho mob hauv Shanghai, Suav teb. Thaum kawg, 771 tus neeg koom nrog tau txais VV116 (384, 600 mg txhua 12 teev rau hnub 1 thiab 300 mg txhua 12 teev rau hnub 2-5) lossis Paxovid (387, 300 mg nimatuvir + 100 mg ritonavir txhua 12 teev rau 5 hnub) ua tshuaj noj.

Cov txiaj ntsig ntawm txoj kev tshawb fawb no qhia tau tias kev kho mob thaum ntxov nrog VV116 rau COVID-19 me me mus rau nruab nrab tau ua tiav qhov kawg tseem ceeb (lub sijhawm kom rov zoo los ntawm kev kho mob) uas tau kwv yees los ntawm cov txheej txheem kho mob: lub sijhawm nruab nrab kom rov zoo los ntawm kev kho mob yog 4 hnub hauv pawg VV116 thiab 5 hnub hauv pawg Paxlovid (qhov piv txwv txaus ntshai, 1.17; 95% CI, 1.02 txog 1.36; qhov txwv qis dua. >0.8).

Tswj lub sijhawm rov zoo los ntawm kev kho mob

Cov ntsiab lus tseem ceeb thiab theem ob ntawm kev ua tau zoo (kev tshuaj xyuas tag nrho ntawm cov pej xeem)

Duab los ntawm: Siv 2

Hais txog kev nyab xeeb, cov neeg koom nrog uas tau txais VV116 tau tshaj tawm tias muaj tsawg dua qhov tshwm sim tsis zoo (67.4%) dua li cov neeg uas tau txais Paxlovid (77.3%) ntawm 28 hnub tom qab kev saib xyuas, thiab qhov tshwm sim ntawm Qib 3 / 4 qhov tshwm sim tsis zoo qis dua rau VV116 (2.6%) dua li rau Paxlovid (5.7%).

Cov xwm txheej tsis zoo (cov neeg muaj kev nyab xeeb)

Duab los ntawm: Siv 2

Kev sib cav sib ceg thiab cov lus nug

Thaum Lub Tsib Hlis 23, 2022, Juniper tau tshaj tawm tias Kev Tshawb Fawb Txog Kev Kho Mob Theem III ntawm VV116 piv rau PAXLOVID rau kev kho mob thaum ntxov ntawm COVID-19 me me mus rau nruab nrab (NCT05341609) tau ntsib nws qhov kawg ntawm kev tshawb fawb.

Duab los ntawm: Siv 1

Thaum lub sijhawm uas cov ntsiab lus ntawm qhov kev sim tsis txaus, qhov kev tsis sib haum xeeb nyob ib puag ncig txoj kev tshawb fawb Theem III yog ob qho: thawj zaug, nws yog kev tshawb fawb ib leeg dig muag thiab, yog tias tsis muaj kev tswj hwm placebo, nws ntshai tias nws yuav nyuaj rau txiav txim siab cov tshuaj kom meej; qhov thib ob, muaj cov lus nug txog cov ntsiab lus kho mob.

Cov qauv kev suav nrog hauv kev kho mob rau Juniper yog (i) cov txiaj ntsig zoo rau qhov kev xeem tshiab, (ii) ib lossis ntau cov tsos mob COVID-19 me me lossis nruab nrab, thiab (iii) cov neeg mob uas muaj feem yuav mob COVID-19 hnyav, suav nrog kev tuag. Txawm li cas los xij, qhov kawg tseem ceeb hauv kev kho mob yog 'lub sijhawm kom rov zoo los ntawm kev kho mob'.

Ua ntej qhov kev tshaj tawm, thaum lub Tsib Hlis 14, Juniper tau kho dua cov ntsiab lus kho mob los ntawm kev tshem tawm ib qho ntawm cov ntsiab lus kho mob tseem ceeb, "feem pua ​​​​​​ntawm kev hloov pauv mus rau kev mob hnyav lossis kev tuag" [3].

Duab los ntawm: Siv 1

Ob lub ntsiab lus tseem ceeb ntawm kev sib cav no kuj tau hais txog tshwj xeeb hauv kev tshawb fawb uas tau luam tawm.

Vim muaj tus kab mob Omicron kis sai sai, kev tsim cov tshuaj placebo rau Paxlovid tsis tau ua tiav ua ntej pib qhov kev sim thiab yog li ntawd cov kws tshawb nrhiav tsis tuaj yeem ua qhov kev sim no siv ob-blind, ob-mock tsim. Raws li qhov ib-blind ntawm qhov kev sim tshuaj, Juniper tau hais tias cov txheej txheem tau ua tom qab kev sib txuas lus nrog cov tub ceev xwm tswj hwm thiab tias ib-blind tsim txhais tau tias tsis yog tus kws tshawb nrhiav (suav nrog tus neeg ntsuam xyuas ntawm qhov kawg ntawm kev tshawb fawb) lossis tus txhawb nqa yuav paub txog kev faib tshuaj kho mob tshwj xeeb kom txog thaum lub hauv paus ntaub ntawv kawg raug kaw thaum kawg ntawm kev tshawb fawb.

Txog thaum lub sijhawm tshuaj xyuas zaum kawg, tsis muaj ib tus neeg koom nrog hauv kev sim siab tau ntsib kev tuag lossis kev nce qib mus rau qhov xwm txheej Covid-19 hnyav, yog li tsis muaj qhov xaus lus tuaj yeem kos txog qhov ua tau zoo ntawm VV116 hauv kev tiv thaiv kev nce qib mus rau qhov hnyav lossis tseem ceeb Covid-19 lossis kev tuag. Cov ntaub ntawv qhia tau hais tias lub sijhawm kwv yees nruab nrab los ntawm kev xaiv mus rau kev rov qab los ntawm cov tsos mob ntsig txog Covid-19 yog 7 hnub (95% CI, 7 txog 8) hauv ob pawg (qhov piv txwv txaus ntshai, 1.06; 95% CI, 0.91 txog 1.22) [2]. Nws tsis nyuaj rau piav qhia vim li cas qhov kawg tseem ceeb ntawm 'tus nqi hloov pauv mus rau kev mob hnyav lossis kev tuag', uas tau teeb tsa ua ntej qhov kawg ntawm kev sim siab, tau raug tshem tawm.

Thaum Lub Tsib Hlis 18, 2022, phau ntawv xov xwm Emerging Microbes & Infections tau tshaj tawm cov txiaj ntsig ntawm thawj qhov kev sim tshuaj ntawm VV116 hauv cov neeg mob uas muaj tus kab mob Omicron variant [4], kev tshawb fawb qhib, kev cia siab nrog 136 tus neeg mob hauv tsev kho mob.

Cov ntaub ntawv los ntawm kev tshawb fawb qhia tau tias cov neeg mob uas muaj tus kab mob Omicron uas siv VV116 hauv 5 hnub ntawm lawv thawj zaug kuaj nucleic acid muaj lub sijhawm rov qab los ntawm nucleic acid ntawm 8.56 hnub, tsawg dua 11.13 hnub hauv pawg tswj. Kev siv VV116 rau cov neeg mob uas muaj tsos mob hauv lub sijhawm ntawm kev tshawb fawb no (2-10 hnub ntawm thawj zaug kuaj nucleic acid) txo lub sijhawm rov qab los ntawm nucleic acid hauv txhua tus neeg mob. Hais txog kev nyab xeeb ntawm tshuaj, tsis muaj kev phiv loj heev tau pom hauv pawg kho mob VV116.

Duab los ntawm: Siv 4

Muaj peb qhov kev sim tshuaj kho mob uas tseem tab tom ua ntawm VV116, ob qho ntawm cov no yog kev tshawb fawb theem III ntawm COVID-19 me me mus rau nruab nrab (NCT05242042, NCT05582629). Lwm qhov kev sim rau COVID-19 nruab nrab mus rau hnyav yog kev tshawb fawb thoob ntiaj teb ntau lub chaw, randomized, ob-dig muag theem III (NCT05279235) los ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm VV116 piv rau kev kho mob tus qauv. Raws li Juniper tshaj tawm, thawj tus neeg mob tau sau npe thiab txhaj tshuaj rau lub Peb Hlis 2022.

Duab los ntawm: clinicaltrials.gov

Cov ntaub ntawv siv:

[1] Junshi Biotech: Tshaj tawm txog qhov kawg tseem ceeb ntawm Theem III kev tshawb fawb txog kev kho mob VV116 piv rau PAXLOVID rau kev kho mob thaum ntxov ntawm COVID-19 me me mus rau nruab nrab

[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, Xu Zhang, Yi, Zhang, 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) Omicron kab mob profile thiab txhaj tshuaj tiv thaiv kab mob ntawm 1881 cov neeg tau txais daim siab hloov pauv: ntau qhov chaw ua haujlwm rov qab los. Emerging Microbes & Infections 11:1, nplooj 2636-2644.