Efficacy and Safety of 8- Versus 12-week Sofosbuvir-ravidasvir Treatment of Non-cirrhotic Chronic Hepatitis C Patients: An Open-label, Randomized, Multicenter Study in Malaysia

This is open-label, randomized, multicentre study to compare the efficacy and safety of the 8-week versus 12-week of SOF-RVD combination treatment for non-cirrhotic chronic hepatitis C patients.
All the recruited subjects will receive the treatment accordingly and be followed up for 24 weeks following the completion of treatment.

Start Date23 Mar 2021

Sponsor / Collaborator-

ISRCTN21085622 / CompletedPhase 2/3

Randomized, open-label, prospective study to evaluate the safety and efficacy of sofosbuvir plus daclatasvir or ravidasvir in Egyptian adults with COVID-19

Start Date29 Sep 2020

Sponsor / Collaborator

European Egyptian Pharmaceutical Industry

NCT04358523 / CompletedPhase 1

Drug Interaction Between RDV and SOF in ASC18 Tablets (RDV/SOF Compound Tablets) and the Influence of Food Effect on the Pharmacokinetics of ASC18 Tablets Were Evaluated in Healthy Subjects. Comparison of the Pharmacokinetic Parameters of ASC18 Tablets（Ravidasvir and Sofosbuvir Fixed Dose Combination）With Reference Tablets (Ravidasvir Sofosbuvir) in Healthy Subjects After Single and Multiple Oral Dosing

The objective of this study is to evaluate potential drug interaction between RDV and SOF in ASC18 tablets (RDV/SOF compound tablets) and the influence of food effect on the pharmacokinetics of ASC18 tablets were evaluated in healthy subjects -and compare the pharmacokinetic parameters of ASC18 tablets（ravidasvir and sofosbuvir fixed dose combination）with ravidasvir tablets and sofosbuvir tablets in healthy subjects after single and multiple oral dosing.

Start Date20 Mar 2020

Sponsor / Collaborator

Ascletis Pharmaceuticals Co.,Ltd.

100 Clinical Results associated with Ravidasvir Hydrochloride

100 Translational Medicine associated with Ravidasvir Hydrochloride

100 Patents (Medical) associated with Ravidasvir Hydrochloride

Literatures (Medical) associated with Ravidasvir Hydrochloride

09 Jul 2024·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Population pharmacokinetics of ravidasvir in adults with chronic hepatitis C virus infection and impact of antiretroviral treatment

Article

Author: Salvadori, Nicolas ; Thongsawat, Satawat ; Avihingsanon, Anchalee ; Thanprasertsuk, Sombat ; Menétrey, Caroline ; Swanson, Alistair ; Panjasawatwong, Navarat ; Ribeiro, Isabela ; Cressey, Tim R. ; Tan, Soek-Siam ; Gillon, Jean-Yves

ABSTRACT:

Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%–60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.

01 Aug 2023·Bioorganic & medicinal chemistry letters

Discovery of potent NAMPT-Targeting PROTACs using FK866 as the warhead

Article

Author: Zhang, Peifeng ; Guo, Menglu ; Xu, Defeng ; Sheng, Chunquan ; Wang, Wei ; Dong, Guoqiang ; Zhou, Luozhu

Nicotinamide phosphoribosyltransferase (NAMPT) has emerged as a promising target for cancer therapy due to its strong correlation with nicotinamide adenine dinucleotide (NAD⁺) metabolism and tumorigenesis. Proteolysis targeting chimeras (PROTACs) provided an attractive strategy for developing NAMPT-targeting NAD⁺-depleting cancer drugs. Herein, a series of von Hippel-Lindau (VHL)-recruiting NAMPT-targeting PROTACs were designed using NAMPT inhibitor FK866 as the warhead. Among them, compound C5 degraded NAMPT (DC₅₀ = 31.7 nM) in a VHL- and proteasome-dependent manner. Moreover, compound C5 effectively inhibited the proliferation of A2780 cells (IC₅₀ = 30.6 nM) and significantly reduced the general cytotoxicity of FK866 to normal cells.

17 May 2023·ACS chemical neuroscience

Antiferroptotic Activities of Oxindole GIF-0726-r Derivatives: Involvement of Ferrous Iron Coordination and Free-Radical Scavenging Capacities.

Article

Author: Takemori, Hiroshi ; Hirata, Yoko ; Hamamoto, Akie ; Furuta, Kyoji ; Takahashi, Mayu ; Oh-Hashi, Kentaro

Ferroptosis and oxytosis are iron- and oxidative stress-dependent cell death pathways strongly implicated in neurodegenerative diseases, cancers, and metabolic disorders. Therefore, specific inhibitors may have broad clinical applications. We previously reported that 3-[4-(dimethylamino)benzyl]-2-oxindole (GIF-0726-r) and derivatives protected the mouse hippocampal cell line HT22 against oxytosis/ferroptosis by suppressing reactive oxygen species (ROS) accumulation. In this study, we evaluated the biological activities of GIF-0726-r derivatives with modifications at the oxindole skeleton and other positions. The addition of a methyl, nitro, or bromo group to C-5 of the oxindole skeleton enhanced antiferroptotic efficacy on HT22 cells during membrane cystine-glutamate antiporter inhibition and ensued intracellular glutathione depletion. In contrast, the substitution of the dimethylamino group on the side chain phenyl ring with a methyl, nitro, or amine group dramatically suppressed antiferroptotic activity regardless of other modifications. Compounds with antiferroptotic activity also directly scavenged ROS and decreased free ferrous ions in both HT22 cells and cell-free reactions while those compounds without antiferroptotic activity had little effect on either ROS or ferrous-ion concentration. Unlike oxindole compounds, which we have previously reported, the antiferroptotic compounds had little effect on the nuclear factor erythroid-2-related factor 2-antioxidant response element pathway. Oxindole GIF-0726-r derivatives with a 4-(dimethylamino)benzyl moiety at C-3 and some types of bulky group at C-5 (whether electron-donating or electron-withdrawing) can suppress ferroptosis, warranting safety and efficacy evaluations in animal models of disease.

News (Medical) associated with Ravidasvir Hydrochloride

27 Jul 2023

·www.pmlive.com

World Health Organization publishes updated essential medicines list

The World Health Organization (WHO) has published updated editions of the Model Lists of Essential Medicines (EML) and Essential Medicines for Children (EMLc) that contain new medicines for the treatment of multiple sclerosis (MS), cancer, infectious diseases, and cardiovascular conditions, among others. The new Model Lists intends to grant better access to innovative medicines that show major clinical benefits, impacting public health globally without affecting the health budgets of low- and middle-income countries. Dr Tedros Adhanom Ghebreyesus, WHO director-general, said: "For over 40 years, countries all over the world have relied on the WHO EML as a definitive, evidence-based guide [for] the most important medicines for delivering the biggest health impact." The new recommendations consist of 85 applications spanning over 100 medicines and formulations that were considered by the WHO Expert Committee on Selection and Use of Essential Medicines. The recent changes have brought the total number of medicines enlisted on the EML and EMLc to a total of 502 and 361, respectively. MS, a chronic and debilitating disease of the nervous system that affects approximately 2.8 million people globally, previously had no medicines for its treatment included on the EML. Three medicines to delay or slow MS progression – cladribine, glatiramer acetate and rituximab – have now been added. Multiple fixed-dose combinations of cardiovascular medicines for the prevention of diseases of the heart and blood vessels, have also been added to the EML for the first time after multiple countries conducted milestone trials confirming the benefits of these combinations for primary and secondary prevention of heart disease. Four new medicines have been listed for infectious diseases, including ravidasvir for the treatment of chronic hepatitis C virus infection in adults, as well as pretomanid for the treatment of multi-drug resistant or rifampicin-resistant tuberculosis. Pegylated liposomal doxorubicin and pegfilgrastim, two new cancer treatments, were added to the ECL, along with new medicines to include new types of childhood cancers on the EMLc. Other listings also include new medications for conditions including diabetes and mental health, as well as essential medicines for children. Dr Benedikt Huttner, secretariat of the WHO EML, described the list as an "important tool for achieving universal health coverage", adding that it provides "guidance to governments, health facilities and procurers on which medicines are the best value in terms of benefits for individuals and communities".

NDA

26 Jun 2023

·www.prnewswire.com

Ascletis Announces Poster Presentation of Phase II Study of ASC42 FXR Agonist for Functional Cure of Chronic Hepatitis B at EASL CONGRESS 2023

HANGZHOU and SHAOXING, China, June 25, 2023 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, "Ascletis") today announces the poster presentation of ASC42, a novel farnesoid X receptor (FXR) agonist, in combination with PEGylated interferon (PEG-IFN) and entecavir (ETV) in chronic hepatitis B (CHB) patients with 12-week treatment at European Association for the Study of the Liver (EASL) CONGRESS 2023. The summary of the abstract is shown as below: Title: A phase 2 study of ASC42, a novel farnesoid X receptor (FXR) agonist, in combination with PEGylated interferon (PEG-IFN) and entecavir (ETV) in chronic hepatitis B patients with 12-week treatment Presenter: Jinzi J. Wu, Ph.D. Principal Investigator: Prof. Jinlin Hou, Nanfang Hospital of Southern Medical University Poster Number: SAT-201 Category: Viral Hepatitis B and D Study Design: This Phase 2 trial (NCT05107778) was a multi-center, randomized, single-blind, placebo-controlled study conducted in China. Forty-three HBeAg negative, hepatitis B virus (HBV) DNA Results: In total, 122, 119, and 107 adverse events (AEs) were reported in 10 mg ASC42, 15 mg ASC42 and PBO cohorts, respectively, and most AEs (94.3%) were mild (grade 1) or moderate (grade 2) in severity. One subject in 15 mg ASC42 cohort experienced a grade 3 serious AE (SAE) of liver function injury with a final outcome of recovered. Pruritus is the most common AE, and study drug-related pruritus was reported in 1 (6.7%), 7 (50%) and 0 (0%) subjects in 10 mg ASC42, 15 mg ASC42 and PBO cohorts, respectively. Pruritus rate of 10 mg ASC42 (6.7%) is lower than other FXR agonists in non-alcoholic steatohepatitis (NASH) patients. Conclusion: In CHB patients, 12-week treatment of 10 mg ASC42 in combination of PEG-IFN-α-2a and ETV was safe and well-tolerated and showed minimum and mild pruritus (6.7%). Previous study indicated that in healthy subjects, 14-day treatment of ASC42 alone demonstrated 471%~1,780% increase of fibroblast growth factor 19 (FGF19) and 53%~91% decrease of 7α-hydroxy-4-cholesten-3-one (C4) at a dose range of 5 mg~15 mg. Data suggest that at the therapeutic dose of 10 mg, the novel FXR agonist ASC42 is differentiated from other FXR agonists in terms of pruritus. [1]. Data on file [2]. Younossi Z.M., Ratziu V., Loomba R., et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial [J]. The Lancet, 2019, 394(10215): 2184-96.DOI: 10.1016/s0140-6736(19)33041-7 [3]. Lau G.K., Piratvisuth T., Luo K.X., et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B [J]. N Engl J Med, 2005, 352(26): 2682-95.DOI: 10.1056/NEJMoa043470 [4]. Loomba R., Noureddin M., Kowdley K.V., et al. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH [J]. Hepatology, 2021, 73(2): 625-43.DOI: 10.1002/hep.31622 [5]. Anstee Q.M., Lucas K.J., Francque S., et al. Tropifexor plus cenicriviroc combination versus monotherapy in non-alcoholic steatohepatitis: Results from the Phase 2b TANDEM study [J]. Hepatology, 2023.DOI: 10.1097/hep.0000000000000439 About EASL EASL, the European Association for the Study of the Liver, founded in 1966, is a medical association dedicated to pursuing excellence in liver research, to the clinical practice of liver disorders, and to providing education to all those interested in hepatology. As of 2022, EASL serves 4,900 members from 112 countries. About Ascletis Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has three marketed products, i.e. ritonavir tablets, GANOVO® and ASCLEVIR®, and 23 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (HBV functional cure), ASC10 and ASC11(oral small molecules for COVID-19 treatment), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne). For more information, please visit . SOURCE Ascletis Pharma Inc.

Clinical ResultPhase 2Phase 3

08 May 2023

·www.prnewswire.com

Ascletis Announces China NMPA Approval of Conducting a Phase IIa Clinical Trial for ASC10 to Treat Respiratory Syncytial Virus Infection

--Respiratory syncytial virus (RSV) infection treatment remains huge unmet medical needs and there is no effective drug for treatment globally so far --Dosage of 800 mg ASC10, twice daily was selected to conduct a Phase IIa study in patients with RSV infection --Preclinical research showed that ASC10-A is a potent inhibitor against RSV both in vitro and in vivo HANGZHOU and SHAOXING, China, May 8, 2023 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces today that the China National Medical Products Administration ("NMPA") has approved to conduct a Phase IIa clinical trial for ASC10 to treat respiratory syncytial virus (RSV) infection. Based on available data, dosage of 800 mg ASC10, twice daily was selected to conduct a randomized, double-blind, placebo-controlled Phase IIa study to evaluate the antiviral activity, safety, tolerability and pharmacokinetics of ASC10 tablets in patients with mild or moderate RSV infection. Ascletis obtained the approval of conducting a Phase IIa clinical trial for ASC10 to treat RSV infection from the U.S. Food and Drug Administration in January 2023. ASC10 is an oral double prodrug. After oral administration, ASC10 is rapidly and completely converted in vivo into the active metabolite ASC10-A, also known as β-D-N4-hydroxycytidine (NHC) or EIDD-1931. Preclinical research[1] showed that ASC10-A (NHC) is a potent inhibitor with EC50 of 0.51 to 0.6 uM against two RSV clinical isolates using in vitro infection assay in HEp-2 cells. Furthermore, preclinical research[1] also demonstrated that ASC10-A (NHC) is efficacious in a mouse RSV infection model. Ascletis has been granted a patent of ASC10 and its derivatives, and their uses to treat multiple virus infections by the United States Patent and Trademark Office (USPTO), including SARS-CoV-2, monkeypox virus and RSV. Globally, RSV affects an estimated 64 million people and causes 160,000 deaths each year[2]. RSV infection treatment remains huge unmet medical needs and there is no effective drug for treatment so far. According to the report from Astute Analytica, the global market of RSV therapies is expected to grow at CAGR of 14.9% from 2022-2027 and reach revenue of US$4.2 billion by 2027[3]. "RSV poses a persistent threat to infants and the elderly population, and so far there is no effective drug available worldwide. We are glad that ASC10 has obtained the China NMPA approval to conduct a Phase IIa study to treat RSV infection in patients, which is a new milestone of Ascletis' R&D in treatment for viral diseases. Preclinical research showed that ASC10-A is a potent inhibitor against RSV both in vitro and in vivo, and we will accelerate the Phase IIa clinical study to benefit patients worldwide." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. [1] Jeong-Joong Yoon, Mart Toots, Sujin Lee, et al. Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses. Antimicrob Agents Chemother. 2018;62(8):e00766-18. [2] [3] About Ascletis Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has three marketed products, i.e. ritonavir tablets, GANOVO® and ASCLEVIR®, and 23 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (HBV functional cure), ASC10 and ASC11(oral small molecules for COVID-19 treatment), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne). For more information, please visit . SOURCE Ascletis Pharma Inc.

Phase 2

100 Deals associated with Ravidasvir Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
-	Ravidasvir Hydrochloride	J05AP	DB15652

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis C	CN	Ascletis Biopharmaceutical (Hangzhou) Co. Ltd.	29 Jul 2020
Hepatitis C	CN	Ascletis Pharma, Inc.	29 Jul 2020

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 3	EG	European Egyptian Pharmaceutical Industry	25 Feb 2020
Chronic hepatitis C genotype 1	Phase 3	CN	Ascletis Biopharmaceutical (Hangzhou) Co. Ltd.	26 Sep 2018
Pseudohyperkalemia Cardiff	Phase 2	-	Ascletis Pharmaceuticals Co.,Ltd.	01 Aug 2015
Hepatitis C, Chronic	Phase 2	US	Presidio Pharmaceuticals, Inc.	01 May 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03020095 (EVEREST, CTgov)	Phase 2	Chronic hepatitis C genotype 1 \| Pseudohyperkalemia Cardiff	38	Danoprevir+Ravidasvir+Ritonavir+Ribavirin	hkmondolhz(siscptbktz) = vrxpuxzmcz rtblncngbs (qynfuvatag, sczbxnfhoo - qjlifsnfcv) View more	-	22 Oct 2020
NCT03362814 (Pubmed \| J Clin Transl Hepatol) Manual	Phase 2/3	Hepatitis C	424	Ravidasvir +ritonavir+danoprevir+ribavirin	bolldhhybo(lxpcuyqoqp) = nkgrwglkoo yfsgwjjaqi (mpvtvzzqxj, 97 - 100) View more	Positive	28 Sep 2019
NCT03362814 (phase 2/3, EASL2019)	Phase 2/3	Chronic hepatitis C genotype 1 NS5A RASs \| IL-28B CC genotype	424	Ravidasvir 200 mg	cvffrdnxes(gyksiqlwkw) = mkcqomjewt gdjjdddleq (rdrtxbisgr ) View more	Positive	11 Apr 2019
NCT03362814 (phase 2/3, EASL2019)	Phase 2/3		424	Danoprevir 100 mg/100 mg	cvffrdnxes(gyksiqlwkw) = zdjhvesydu gdjjdddleq (rdrtxbisgr )	Positive	11 Apr 2019
NCT03020095 (EVEREST, Pubmed \| J Gastroenterol Hepatol) Manual	Phase 2	Hepatitis C	38	Ravidasvir +danoprevir +ribavirin	nkgbosffuz(qmdfpvcymw) = zuyvnxcsdt jjoadjktsu (qcdnghirlj ) View more	Positive	01 Aug 2018
NCT02371408 (Pubmed \| J Hepatol)	Phase 2/3	Hepatitis C, Chronic	300	Ravidasvir plus Sofosbuvir	xcmdgugebg(jglzcvyisk) = pfqzfukywu vurdmyxjxs (vmjdwnuhhg )	Positive	19 Sep 2017

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