RESULTS
obesity, sore throat, cardiovascular disease, TEAEs, cough, migraine, diabetes
OBESITY, SORE THROAT, VIRUS, CARDIOVASCULAR DISEASE, ADVERSE EVENTS, ADVERSE DRUG REACTIONS, EVENT, CHRONIC RESPIRATORY DISEASE, MAY, PLAQUE, REGRESSION, HIGH BLOOD PRESSURE, MIGRAINE, DIABETES
A total of 365 patients from 21 institutions in South Korea were assessed between February and May 2021, and 342 patients were enrolled in the study (Enrollment and randomization.Of the 342 randomized patients, a total of 323 patients (161 in the camostat group and 162 in the placebo group), excluding 15 who did not receive investigational products and 4 who missed the “Efficacy Variables Check,” were included in the full analysis set (FAS). A total number of 245 patients (116 in the camostat group and 129 in the placebo group), excluding 78 patients from the FAS (6 due to “Inclusion Criteria Deviation,” 1 due to “Exclusion Criteria Deviation,” and 71 due to “IP Handling and Administration”), was included in the modified full analysis set (mFAS). The median age was 53.0 years in the camostat group and 53.5 years in the placebo group, and 53.22% (182/342) were male. In all, 54.39% (186/342) had one or more risk factors, such as cardiovascular disease, chronic respiratory disease, high blood pressure, diabetes, obesity, and smoking, of which 55.81% (96/172) were in the camostat group and 52.94% (90/170) in the placebo group. At baseline, 72.22% (247/342) had a mild and 27.78% (95/342) had a moderate severity of COVID-19 (Demographics and baseline characteristics of the randomized setMin, minimum; max, maximum; BMI, body mass index; NEWS, national early warning score.See the description of the randomized set in Results. For the data below, unless otherwise indicated, the denominator of the percentage is the number of subjects in each group.Testing for difference between DWJ1248 and placebo using two-sample Testing for difference between DWJ1248 and placebo using chi-square test (c) or Fisher’s exact test (f).The denominator of the percentage for individual risk factors is the number of subjects with the risk factor in each group.The denominator of the percentage for COVID-19 antibody is the number of subjects who had a positive result for COVID-19 antibody in each group.The primary endpoint, time to clinical improvement of subject symptoms within 14 days, was not significantly different between the two groups, being 7 days in the camostat group and 8 days in the placebo group (95% confidence interval [CI], 0.84 to 1.43; Kaplan-Meier plot for time to clinical improvement of subjective symptoms.Clinical improvement in subjective symptoms in the FASFAS, full analysis set. See the description of the FAS in Results.Min, minimum; max, maximum; CI, confidence interval.The denominator of the percentage is the number of subjects who have symptoms at baseline for each group.Duration (days) = (date of event/censored, whichever occurs first − date of first IP administration +1); status = event (clinical improvement) if there is clinical improvement at least once by day 14, and status = censored (no clinical improvement) if there is no improvement by day 14 but clinical improvement after day 14 or no improvement by the end of the study or there is rescue therapy usage before clinical improvement by day 14.Testing for difference between DWJ1248 and placebo using the log rank test.Testing for difference between DWJ1248 and placebo using the Cox proportional hazards model with treatment group as a factor and age and risk factor as covariates. If the result or CI was estimated to be infinity, hazard ratio was estimated using Firth’s penalized maximum likelihood and its CI was presented as the profile penalized likelihood confidence interval.The median time to clinical improvement and its 95% confidence interval by treatment group using the Kaplan-Meier curve.In the FAS of the high-risk group, the proportions with improvement of subjective symptoms by day 7 were 45.87% (50/109) and 38.46% (40/104) in the camostat group and the placebo group, respectively (95% CI, 0.77 to 2.31; Clinical improvement of subjective symptoms in high-risk group in the FAS and the mFASFAS, full analysis set; mFAS, modified full analysis set. See the descriptions of the FAS and the mFAS in Results.The denominator of the percentage is the number of subjects in each group.Testing for difference between treatment groups using the chi-square test.Odds ratio was estimated using Firth’s penalized maximum likelihood, and its CI was presented as the profile penalized likelihood confidence interval.Testing for difference between treatment groups using the logistic regression model with treatment group as a factor and age and risk factor as a covariate.In the high-risk group, the ordinal scale score improved by day 7 in 20.00% (18/90) of the camostat group in the FAS, compared to 13.33% (12/90) of the placebo group (95% CI, 0.75 to 3.78; Improvement in ordinal scale in high-risk group in the FAS and the mFASFAS, full analysis set; mFAS, modified full analysis set. See the descriptions of the FAS and the mFAS in Results.The denominator of the percentage is the number of subjects in each group.Testing for difference between treatment groups using the chi-square test.Odds ratio was estimated using Firth’s penalized maximum likelihood, and its confidence interval (CI) is presented as the profile penalized likelihood confidence interval.Testing for difference between treatment groups using the logistic regression model with treatment group as a factor and age and risk factor as a covariate.Virus culture was previously planned as an exploratory endpoint in this study’s protocol. The virus culture test was performed on swab samples obtained from the nasopharynx. For the quantification of SARS-CoV-2, nasopharyngeal swab samples were taken at predetermined intervals. All the clinical samples were transferred to a single central laboratory and were analyzed there. SARS-CoV-2 culture was performed and viral titers were assessed as described previously (Virus culture using plaque assay in SARS-CoV-2-infected patient samples. Error bars show standard deviations.Concomitant medications (Piroxicam patch and Diphenhydramine Hydrochloride patch) used included analgesics, antibiotics, antihistamine, nonsteroidal anti-inflammatory drugs (NSAIDs), cough medicine, sore throat medicine, muscle relaxant, patch, migraine reliever, and analgesic or cough medicine. The proportions of patients receiving the concomitant medications were not significantly different in the two groups, supporting the conclusion that taking camostat mesylate contributed to the improvement in patients’ clinical symptoms, rather than taking other standard-of-care medications (Table S2). Although not statistically different, 60.47% (104/172) of the camostat group and 68.82% (117/170) of the placebo group received cough medicine (95% CI, 59.55 to 69.69; The rates of incidence of treatment emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were not statistically different between the camostat and placebo groups (Incidence of TEAEs and ADRs (safety set)The denominator of the percentage is the number of subjects in each group.Testing for difference between treatment groups using the chi-square test.