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

Study Overview
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Brief Summary
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This study is a placebo-controlled, Phase 2a proof-of-concept clinical study which will evaluate efficacy and safety of dalcetrapib in outpatients patients with mild to moderate, symptomatic, confirmed COVID 19.

Official Title
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A Double-blind, Placebo-controlled, Phase 2a Proof-of-concept Trial of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: Dalcetrapib
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must satisfy all of the following criteria unless otherwise stated: Willing and able to provide informed consent Male or female patients > 18 years of age on the day of informed consent Have received a confirmed diagnosis of COVID-19 (positive for SARS CoV 2), as assessed by PCR or point-of-care within 72 hours of first dose on Day 1 Have mild to moderate signs or symptoms of COVID-19 with onset within 5 days of first dose on Day 1, at least two of the following symptoms: stuffy or runny nose sore throat shortness of breath cough fatigue myalgia headache chills or shivering feeling hot or feverish nausea vomiting diarrhea anosmia ageusia Outpatient with COVID-19 disease (not requiring oxygen therapy [WHO COVID-19 Clinical Improvement Ordinal Scale, score of 3]) Patient is aware of the investigational nature of this study and willing to comply with protocol treatments, blood tests, and other evaluations listed in the informed consent form (ICF). Exclusion Criteria: Patients will be excluded from the study if they satisfy any of the following criteria unless otherwise stated: Females who are pregnant (negative pregnancy test required for all women of child bearing potential at Screening) or breast-feeding Male patients and women of childbearing potential (women who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least one protocol specified method of contraception Severe COVID-19 disease as defined by the WHO COVID-19 Clinical Improvement Ordinal Scale, scores of 5 (non invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation), or 7 (ventilation + additional organ support pressors, renal replacement therapy [RRT], extracorporeal membrane oxygenation [ECMO]) Expected survival less than 72 hours Peripheral capillary oxygen saturation (SpO2) <90% while breathing room air Treatment with other drugs thought to possibly have activity against SARS CoV 2 infection like remdesivir, favipiravir, within 7 days prior to enrollment or concurrently History of abuse of drugs or alcohol that could interfere with adherence to study requirements as judged by the Investigator Use of any other concurrent investigational drugs while participating in the present study Patient requires frequent or prolonged use of systemic corticosteroids (≥20 mg of prednisone/day or equivalent for >4 weeks) or other immunosuppressive drugs (e.g., for organ transplantation or autoimmune conditions) Known renal disease with an estimated glomerular filtration rate (eGFR) <50 mL/min based on local laboratory results Patients with clinically apparent liver disease, e.g., jaundice, cholestasis, hepatic synthetic impairment, or active hepatitis Alanine transaminase (ALT) or aspartate transaminase (AST) >3 × upper limit of normal (ULN) or alkaline phosphatase or bilirubin levels > 2 × ULN based on local laboratory results Co administration of clinical doses of orlistat with dalcetrapib Inability to swallow oral medications or a gastrointestinal disorder with diarrhea (e.g., Crohn's disease) or malabsorption at Screening Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the Investigator, would jeopardize the safety of the patient or potentially impact patient compliance or the safety/efficacy observations in the study History of an allergic reaction or hypersensitivity to the study drug or any component of the study drug formulation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, double blind, multicenter, Phase 2a proof-of-concept study in outpatients with confirmed, mild to moderate, symptomatic COVID-19.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 900 mg dose<br>Patients will receive Dalcetrapib 900 mg for 10 days | Drug: Dalcetrapib<br>* Dalcetrapib 300 mg Film-Coated Tablets<br>|
| Active Comparator: 1800 mg dose<br>Patients will receive Dalcetrapib 1800 mg for 10 days | Drug: Dalcetrapib<br>* Dalcetrapib 300 mg Film-Coated Tablets<br>|
| Active Comparator: 3600 mg dose<br>Patients will receive Dalcetrapib 3600 mg for 10 days | Drug: Dalcetrapib<br>* Dalcetrapib 300 mg Film-Coated Tablets<br>|
| Placebo Comparator: Placebo tablets<br>Patients will receive Placebo for 10 days | Other: Placebo<br>* Placebo Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Sustained Clinical Resolution of Symptoms of COVID-19 (Excluding Cough, Sense of Smell and Taste) in Subjects With Confirmed, Mild to Moderate, Symptomatic COVID-19 Treatment With Dalcetrapib | 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. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in log10 Viral Load (Saliva) | 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. | Screening/Baseline (Day -2 to Day -1), Day 3, Day 5, Day 10, and Day 28/End of Study (EOS) | 
| Change From Baseline in log10 Viral Load (Nasal Swab) | 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. | Screening/Baseline (Day -2 to Day -1), Day 3, Day 5, Day 10, and Day 28/End of Study (EOS) | 
| Time to Sustained Complete Clinical Resolution of Symptoms in Subjects With Confirmed, Mild to Moderate, Symptomatic COVID-19 Treatment With Dalcetrapib | 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. | 28 days | 
| Viral Clearance Using Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) Polymerase Chain Reaction (PCR) | 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. | Day 1 to Day 28 | 
| Time to Complete Clinical Resolution (Excluding Cough, Sense of Smell and Taste) Defined in the Same Way as the Primary Endpoint, But Considering That All Symptoms Must Resolve to a Score of 0 for 72 Hours | 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. | 28 days | 
| Time to Complete Clinical Resolution | 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. | 28 days | 
| Change From Baseline in Coronavirus Disease of 2019 (COVID-19) Total Symptom Severity Score Collected at All Time Points | 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. | 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) | 
| Scoring of World Health Organization (WHO) Clinical Outcome Scale (9-point Scale) at Screening, Days 1, 3, 5, End of Treatment (Day 10), Follow-Up Visit (Day 14), and 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. | Screening (Day -2 to Day -1), Days 1, 3, 5, End of Treatment (Day 10), Follow-Up Visit (Day 14), and Day 28 | 
| Rate of Hospitalization Through 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. | Day 1 to Day 28 | 
| Rate of Progression to Oxygen Therapy Through 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. | Day 1 to Day 28 | 
| Type of Oxygen Therapy Received Through Day 28 | 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. | Day 1 to Day 28 | 
| Duration of Hospitalization | 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. | Day 1 through Day 28 | 
| Mortality Rate by Day 28 | 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. | Day 1 to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Coronavirus disease, Dalcetrapib