Serial Viral Load Analysis by Ddpcr to Evaluate Fnc Efficacy and Safety in the Treatment of Moderate Cases of Covid-19

Abstract

A highly pathogenic coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 causing coronavirus disease 2019 (COVID-19). Trials have been carried out to find drugs effective in fighting the disease, as COVID-19 is being considered a treatable disease only after we have antivirals. A clinical candidate originally developed for HIV treatment, AZVUDINE (FNC), is a promising drug in the treatment of COVID-19, being able to reduce the patient's viral load leading to cure. In this study, a randomized clinical trial was performed in moderate COVID-19 patients to evaluate the efficacy of FNC added to standard treatment, compared with placebo group added to standard treatment. RT-qPCR and ddPCR were applied to estimate the viral load in samples from patients, which was performed every 48 hours throughout the treatment. Also, the clinical improvement was evaluated as well as the liver and kidney function. Notably, FNC treatment in moderate COVID-19 patients may shorten the time of nucleic acid negativity conversion versus placebo group, accelerates the elimination of the virus, decreasing the viral load significantly, especially in the first days. Due to the lack of specific antiviral drug, the pandemic is not under the control and resurfaces in different waves of infection, which cause a large cumulative expense of medical resources. Fortunately, FNC could reduce treatment time of moderate COVID-19 patients and save a lot of medical resources, making it a strong candidate for the treatment of COVID-19. Trial registration number: NCT04668235 https://clinicaltrials.gov/ct2/show/NCT04668235?term=azvudine&cond=COVID-19&draw=2&rank=1

A Nearly 20‐Year Journey to Success of Azvudine for Antiviral Therapy

“…In another randomized clinical trial in moderate COVID‐19 patients, Azvudine shortened the time of NANC compared to the placebo group, accelerated virus elimination, and decreased the viral load significantly (trial number: NCT04668235). [ 35 ] No changes were observed for hepatic and renal functions between the FNC and control group, indicating the safety of Azvudine. Similarly, the adverse events of Azvudine were mainly related to the increase in ALT, GGT, AST, and GRADE 1 headache, with normalization of these events until the end of treatment.…”

“…Furthermore, Azvudine demonstrated efficacy against various virus variants, including Alpha, Beta, and Delta. [ 35 ] The patients receiving Azvudine (5 mg per person daily) did not experience increased risk. There were no statistically significant differences in adverse events between the Azvudine and placebo groups.…”

Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials

“…Patients with moderate COVID-19 were randomly assigned with a ratio of 1:1 to receive Azvudine 10 mg once a night plus standard treatment or placebo plus standard treatment. A total of 180 eligible patients with moderate COVID-19 were enrolled, of whom 172 completed the study ( Cabral et al, 2022 ). The results of both phase III clinical trials revealed that Azvudine significantly reduced the NANC time and viral load of the patients compared to the placebo group ( da Silva et al, 2023 ; Cabral et al, 2022 ).…”

“…A total of 180 eligible patients with moderate COVID-19 were enrolled, of whom 172 completed the study ( Cabral et al, 2022 ). The results of both phase III clinical trials revealed that Azvudine significantly reduced the NANC time and viral load of the patients compared to the placebo group ( da Silva et al, 2023 ; Cabral et al, 2022 ).…”

Efficacy and safety evaluation of Azvudine in the treatment of COVID-19 based on four phase Ⅲ clinical trials.

“…The results were detailedly disclosed in the preprints published on the Research Square platform (https://www.researchsquare.com), and showed that Azvudine significantly reduced the time of nucleic acid negative conversion (NANC) as well as the viral load of the patients compared to placebo. 4,5 Taken together, Azvudine could decrease the time of NANC, viral load, and median time to improvement in clinical condition, and increase the proportion of improvement in clinical condition on day 7 in the patients with COVID-19. In addition, Azvudine exhibited good safety and well tolerance as compared to placebo.…”