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

Phase 2

Completed

Conditions: Covid19

Interventions: Other: Placebo
Drug: Dalcetrapib

Registration Number: NCT04676867

Lead Sponsor: DalCor Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 227

Inclusion Criteria

Patients must satisfy all of the following criteria unless otherwise stated:
1. Willing and able to provide informed consent
2. Male or female patients > 18 years of age on the day of informed consent
3. 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
4. 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
5. Outpatient with COVID-19 disease (not requiring oxygen therapy [WHO COVID-19 Clinical Improvement Ordinal Scale, score of 3])
6. 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:
1. Females who are pregnant (negative pregnancy test required for all women of child bearing potential at Screening) or breast-feeding
2. 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
3. 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])
4. Expected survival less than 72 hours
5. Peripheral capillary oxygen saturation (SpO2) <90% while breathing room air
6. 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
7. History of abuse of drugs or alcohol that could interfere with adherence to study requirements as judged by the Investigator
8. Use of any other concurrent investigational drugs while participating in the present study
9. 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)
10. Known renal disease with an estimated glomerular filtration rate (eGFR) <50 mL/min based on local laboratory results
11. Patients with clinically apparent liver disease, e.g., jaundice, cholestasis, hepatic synthetic impairment, or active hepatitis
12. 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
13. Co administration of clinical doses of orlistat with dalcetrapib
14. Inability to swallow oral medications or a gastrointestinal disorder with diarrhea (e.g., Crohn's disease) or malabsorption at Screening
15. 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
16. History of an allergic reaction or hypersensitivity to the study drug or any component of the study drug formulation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo tablets	Placebo	Patients will receive Placebo for 10 days
1800 mg dose	Dalcetrapib	Patients will receive Dalcetrapib 1800 mg for 10 days
900 mg dose	Dalcetrapib	Patients will receive Dalcetrapib 900 mg for 10 days
3600 mg dose	Dalcetrapib	Patients will receive Dalcetrapib 3600 mg for 10 days

Primary Outcome Measures

Name	Time	Method
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	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), 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in log10 Viral Load (Saliva)	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.
Mortality Rate by Day 28	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 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 to Complete Clinical Resolution	28 days	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.
Change From Baseline in log10 Viral Load (Nasal Swab)	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 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 to Sustained Complete Clinical Resolution of Symptoms in Subjects With Confirmed, Mild to Moderate, Symptomatic COVID-19 Treatment With Dalcetrapib	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.
Viral Clearance Using Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) Polymerase Chain Reaction (PCR)	Day 1 to Day 28	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.
Rate of Hospitalization Through Day 28	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.
Rate of Progression to Oxygen Therapy Through Day 28	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.
Duration of Hospitalization	Day 1 through Day 28	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 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	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.
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	Screening (Day -2 to Day -1), 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.
Type of Oxygen Therapy Received Through Day 28	Day 1 to 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.
Change From Baseline in Coronavirus Disease of 2019 (COVID-19) Total Symptom Severity Score Collected at All Time Points	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)	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.