A Phase I Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Severe Kidney Impairment on the Pharmacokinetics, Safety and Tolerability of Leritrelvir(RAY1216)

This study will assess the effect of severe kidney impairment on the pharmacokinetics (PK), safety and tolerability of Leritrelvir.

Start Date26 Sep 2023

Sponsor / Collaborator

Guangdong Zhongsheng Ruichuang Biotechnology Co. Ltd.

NCT06362460 / CompletedPhase 1

Single-center, Open-label, Non-randomized and Single-dose Clinical Trial to Explore the Mass Balance of Oral Suspension of 400mg [14C]RAY1216

This study is a single-center, open-label, and single-dose clinical study to evaluate the mass balance, biotransformation and pharmacokinetics of [14C]RAY1216 in healthy Chinese male participants, revealing the overall pharmacokinetic characteristics of RAY1216.

Start Date18 Sep 2023

Sponsor / Collaborator

Guangdong Zhongsheng Ruichuang Biotechnology Co. Ltd.

NCT06161259 / CompletedPhase 1

A Phase I Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of Leritrelvir(RAY1216)

This study will assess the effect of hepatic impairment on the pharmacokinetics (PK), safety and tolerability of Leritrelvir(RAY1216)

Start Date14 Sep 2023

Sponsor / Collaborator

Guangdong Zhongsheng Ruichuang Biotechnology Co. Ltd.

100 Clinical Results associated with Leritrelvir

100 Translational Medicine associated with Leritrelvir

100 Patents (Medical) associated with Leritrelvir

Literatures (Medical) associated with Leritrelvir

01 Sep 2024·Acta Pharmaceutica Sinica B

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

Article

Author: Wang, Tong-Yun ; Yuen, Kwok-Yung ; Tsang, Jessica Oi-Ling ; Chu, Allen Wing-Ho ; Chan, Wan-Mui ; Qin, Zhenzhi ; Guo, Qian ; Ip, Jonathan Daniel ; Ye, Zi-Wei ; Ni, Tao ; Cui, Sheng ; Tang, Kaiming ; Xie, Yubin ; Chan, Chris Chun-Yiu ; Qin, Bo ; Dai, Mei ; Cai, Jian-Piao ; To, Kelvin Kai-Wang ; Jin, Dong-Yan ; Yuan, Shuofeng ; Wen, Lei ; Ong, Chon Phin ; Chu, Hin ; Cao, Jianli ; Chik, Kenn Ka-Heng ; Chan, Jasper Fuk-Woo ; Huang, Yixin ; Ge, Xing-Yi

There are only eight approved small molecule antiviral drugs for treating COVID-19. Among them, four are nucleotide analogues (remdesivir, JT001, molnupiravir, and azvudine), while the other four are protease inhibitors (nirmatrelvir, ensitrelvir, leritrelvir, and simnotrelvir-ritonavir). Antiviral resistance, unfavourable drug‒drug interaction, and toxicity have been reported in previous studies. Thus there is a dearth of new treatment options for SARS-CoV-2. In this work, a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 activity. One compound, designated 172, demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of concern. Mechanistic studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease (3CLpro) by binding to an allosteric site and reduces 3CLpro dimerization. A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in vitro. In vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 mice. Overall, this study identified an alternative druggable site on the SARS-CoV-2 3CLpro, proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

01 Mar 2024·International Journal of Antimicrobial Agents

Small-molecule antiviral treatments for COVID-19: A systematic review and network meta-analysis

Review

Author: Han, Bing ; Feng, Pinpin ; Zhang, Meiling ; Ying, Yin ; Yang, Bo ; Zhao, Qinqin ; Xin, Chuanwei ; Zhu, Jun ; Li, Gonghua ; Yang, Wenjuan ; Zheng, Bei

OBJECTIVEThis study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19).METHODSSeven databases were searched from their inception to 01 June 2023. The risk of bias in randomised controlled trials and retrospective studies was evaluated individually using the Cochrane risk-of-bias tool and Newcastle Ottawa Scale.RESULTSIn total, 160 studies involving 933 409 COVID-19 patients were evaluated. Compared with placebo or standard of care, proxalutamide demonstrated remarkable efficacy in reducing mortality rates, hospitalisation rates, serious adverse events, and the need for mechanical ventilation. Furthermore, it significantly enhanced both the rate of clinical improvement and expedited the duration of clinical recovery when compared with control groups. In patients with mild-to-moderate COVID-19, proxalutamide exhibited the above advantages, except for mortality reduction. Triazavirin was the most effective treatment for reducing the time required for viral clearance and improving the discharge rate. Leritrelvir and VV116 were ranked first in terms of enhancing the viral clearance rate on days 7 and 14, respectively. Molnupiravir was the most effective treatment for reducing the need for oxygen support. Overall, these findings remained consistent across the various subgroups.CONCLUSIONSA thorough evaluation of effectiveness, applicable to both mild-to-moderate and unstratified populations, highlights the specific advantages of proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 in combating COVID-19. Additional clinical data are required to confirm the efficacy and safety of simnotrelvir/ritonavir and leritrelvir. The safety profiles of these antivirals were deemed acceptable.

01 Jan 2024·eClinicalMedicine

Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial

Article

Author: Zhong, Nanshan ; Pan, Hongqiu ; Lin, Ling ; Zhang, Ping ; Wang, Xifu ; Lu, Hongzhou ; Li, Weiyang ; Liang, Shiwei ; Fang, Zhonghao ; Kang, Changyuan ; Ou, Shuqiang ; Jiang, Mei ; Song, Yudi ; Huang, Chaolin ; Wang, Furong ; Yu, Tao ; Yang, Zifeng ; Su, Liang ; Lin, Zhengshi ; Yao, Herui ; Luo, Jincan ; Li, Yueping ; Meng, Qingwei ; Li, Haijun ; Xu, Ruhong ; Liang, Jingyi ; Chen, Dexiong ; Deng, Ying ; Chen, Ruifeng ; Zhan, Yangqing ; Sun, Ruilin ; Zheng, Jingping ; Zheng, Zhigang ; Zhang, Yu ; Guo, Xiaoyun ; Ge, Fangqi ; Lin, Bingliang ; Tong, Jianlin ; Xiang, Tianxin

BackgroundLeritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19.MethodsThis was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160.FindingsBetween Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95-428.68 h]) than that of Placebo (271.33 h [IQR 219.00-529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07-1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious.InterpretationLeritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns.FundingThis study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

100 Deals associated with Leritrelvir

R&D Status

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Indication	Country/Location	Organization	Date
COVID-19	CN	Guangdong Zhongsheng Ruichuang Biotechnology Co. Ltd.	21 Mar 2023

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Diseases	Phase 1	CN	Guangdong Zhongsheng Ruichuang Biotechnology Co. Ltd.	26 Sep 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05620160 (Pubmed) Manual	Phase 3	COVID-19	1,359	Leritrelvir	(orpruijlxl) = awvfpwlddp acrrgveprk (xzhpcoxird, 188.95 - 428.68) View more	Positive	14 Dec 2023
				Placebo	(orpruijlxl) = qazrdabrhh acrrgveprk (xzhpcoxird, 219.00 - 529.63) View more

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