Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19

Sustained clinical resolution is defined as occurring when no key COVID-19 related symptom has a score higher than 1 over a 72-hour period (as documented using an electronic patient-reported outcome \[ePRO\] instrument), except for sense of smell and taste where the score should be 0 over a 72-hour period. The time to resolution was taken as the time from randomization until the first day of the last 72-hour period where the patient met the definition of resolution within 28 days. Patients who did not meet the definition of resolution 28 days after randomization were considered not resolved. The scale is Assessment of 14 Common COVID-19-Related Symptoms: Items and Response from the Food and Drug Administration (FDA). The symptoms are scored as on a scale of 0 to 3 for 12 of the symptoms where 0 is none and on a scale of 0 to 2 for the two other symptoms where 0 is as usual. A higher score is a worse outcome.

Time frame: 28 days

COVID-19 total symptom severity score was summarized by treatment group using descriptive statistics (N, mean, median, standard deviation, minimum, and maximum) for each visit as well as for changes from baseline where an 80% confidence interval (CI) was also presented. Mean changes from baseline were analyzed using a repeated measures ANCOVA model. The scale is Assessment of 14 Common COVID-19-Related Symptoms: Items and Response from the Food and Drug Administration (FDA) document Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment Guidance for Industry. Symptoms are scored as on a scale of 0 to 3 for 12 the symptoms and on a scale of 0 to 2 for two symptoms. The sum of all 14 symptom scores is reported, where 0 is the minimum and 40 is the maximum. A higher score is a worse outcome.

Time frame: Baseline, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 14 (follow-up visit 1), and Day 28 (end of study / follow-up visit 2)

Population: The number of subjects is different at baseline and at post-baseline visits. The difference in means is therefore not the same as the mean of the differences. The analysis has been conducted on the mean of the differences and the analysis of the change from baseline to Day X is based on subjects who had data at both baseline and Day X visits.

Log10 viral load, as assessed using the nasal swab, was summarized by treatment group using descriptive statistics (N, mean, median, standard deviation, minimum, and maximum) for each visit as well as for changes from baseline where an 80% CI were also presented. A repeated ANCOVA model was used for the data shown below, showing the mean changes from baseline to study visits (Day 3, Day 5, Day 10, and Day 28/EOS) in log10 viral load including treatment groups by study visit interaction, baseline value of log10 viral load and baseline value of log10 viral load by study visit interaction.

Time frame: Screening/Baseline (Day -2 to Day -1), Day 3, Day 5, Day 10, and Day 28/End of Study (EOS)

Log10 viral load, as assessed using the saliva, was summarized by treatment group using descriptive statistics (N, mean, median, standard deviation, minimum, and maximum) for each visit as well as for changes from baseline where an 80% CI were also presented. A repeated ANCOVA model was used for the data shown below, showing the mean changes from baseline to study visits (Day 3, Day 5, Day 10, and Day 28/EOS) in log10 viral load including treatment groups by study visit interaction, baseline value of log10 viral load and baseline value of log10 viral load by study visit interaction.

Time frame: Screening/Baseline (Day -2 to Day -1), Day 3, Day 5, Day 10, and Day 28/End of Study (EOS)

The duration of hospitalization was performed on the intention-to-treat (ITT) population in subjects who were hospitalized. Duration of hospitalization was summarized by treatment group using descriptive statistics (N, mean, median, standard deviation, Q1, Q3, minimum, and maximum). An ANOVA model was performed to analyze the difference between treatment groups. The model included only the treatment group. Contrasts under this model allowed for the comparisons across treatment groups. The results were presented as mean treatment difference with associated 80% confidence interval (CI) and p-value.

Time frame: Day 1 through Day 28

Population: The duration of hospitalization was measured for all participants in the intent-to-treat (ITT) population; however, the mean length of hospitalization for each arm presented here reflects an analysis performed on only the hospitalized subjects from the ITT population.

The analysis of this endpoint was performed on the intention-to-treat (ITT) population. The number and percentage of patients who died was presented. The percentage of patients who died was compared using a binary logistic regression. The model included only the treatment group. Contrasts under this model allowed for the comparisons across treatment groups. The results were presented as odds ratios, with associated 80% CIs and p-values.

Time frame: Day 1 to Day 28

The analysis of this endpoint was performed on the intention-to-treat (ITT) population. The percentage of patients who were hospitalized was compared using a binary logistic regression analysis. The model included only the treatment group. The results were presented as odds ratios, with associated 80% CIs and p-value.

Time frame: Day 1 to Day 28

The analysis of this endpoint was performed on the intention-to-treat (ITT) population. The number and percentage of patients who progressed to oxygen therapy was presented. The percentage of patients who had progressed to oxygen therapy was compared using a binary logistic regression analysis. The model included only the treatment group. The results were presented as odds ratios, with associated 80% confidence intervals (CIs) and p-value.

Time frame: Day 1 to Day 28

The number and percentage of patients for each WHO clinical outcome score was summarized. Scores were compared using the Mann-Whitney-Wilcoxon test. This scale is called the WHO Clinical Outcome Scale. It is scored from 0 to 9 where 9 is the most severe disease presentation. A higher score is a worse outcome.

Time frame: Screening (Day -2 to Day -1), Days 1, 3, 5, End of Treatment (Day 10), Follow-Up Visit (Day 14), and Day 28

Population: Not all subjects completed the trial. World Health Organization Clinical Outcome Scores were not collected for withdrawn subjects beyond their withdrawal date.

Sustained clinical resolution is defined as occurring when no key COVID-19 related symptom has a score higher than 0 over a 72-hour period. The time to resolution was taken as the time from randomization until the first day of the last 72 hour period where the patient met the definition of resolution within 28 days. Patients who did not meet the definition of resolution 28 days after randomization were considered not resolved. The scale is Assessment of 14 Common COVID-19-Related Symptoms: Items and Response was used. The symptoms are scored as on a scale of 0 to 3 for 12 of the symptoms where 0 is none and on a scale of 0 to 2 for the two other symptoms where 0 is as usual. A higher score is a worse outcome. Resolution must have occurred within 28 days. Time of resolution of 29 days was imputed in censored subjects.

Time frame: 28 days

Complete clinical resolution is defined as occurring when no key COVID-19 related symptom (excluding cough, sense of smell and taste) has a score higher than 0 over a 72-hour period. The time to resolution was taken as the time from randomization until the first day of the last 72 hour period where the patient met the definition of resolution within 28 days. Patients who did not meet the definition of resolution 28 days after randomization were considered not resolved. The scale is Assessment of 14 Common COVID-19-Related Symptoms: Items and Response was used. The symptoms are scored as on a scale of 0 to 3 for 12 of the symptoms where 0 is none and on a scale of 0 to 2 for the two other symptoms where 0 is as usual. A higher score is a worse outcome.

Time frame: 28 days

Sustained clinical resolution is defined as occurring when no key COVID-19 related symptom has a score higher than 1 over a 72-hour period (as documented using an electronic patient-reported outcome \[ePRO\] instrument). The time to resolution was taken as the time from randomization until the first day of the last 72-hour period where the patient met the definition of resolution within 28 days. Patients who did not meet the definition of resolution 28 days after randomization were considered not resolved. The scale is Assessment of 14 Common COVID-19-Related Symptoms: Items and Response from the Food and Drug Administration (FDA). The symptoms are scored as on a scale of 0 to 3 for 12 of the symptoms where 0 is none and on a scale of 0 to 2 for the two other symptoms where 0 is as usual. A higher score is a worse outcome.

Time frame: 28 days

The analysis of this endpoint was performed on the intention-to-treat (ITT) population and only on those who received oxygen therapy. The number and percentage of patients who received different types of oxygen therapy was presented using descriptive statistics.

Time frame: Day 1 to Day 28

Population: The type of oxygen therapy received was measured for all participants in the intent-to-treat (ITT) population; however, the data presented here reflects an analysis performed only on those subjects from the ITT population who received oxygen therapy.

Viral clearance based on polymerase chain reaction (PCR) test for Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) using nasal swab and saliva samples was performed on the intention-to-treat (ITT) population. Viral clearance was summarized by treatment group using Kaplan-Meier methods. Median and associated 80% confidence interval (CI) was presented. The number and percentage of patients who did not show viral clearance, did show viral clearance, and patients censored were presented.

Time frame: Day 1 to Day 28

Population: Two subjects were deleted from this analysis as the samples were deemed unreliable by the study site. One subject had no saliva samples analyzed.