Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 900 mg dose Patients will receive Dalcetrapib 900 mg for 10 days |
Drug: Dalcetrapib
Dalcetrapib 300 mg Film-Coated Tablets
|
| Active Comparator: 1800 mg dose Patients will receive Dalcetrapib 1800 mg for 10 days |
Drug: Dalcetrapib
Dalcetrapib 300 mg Film-Coated Tablets
|
| Active Comparator: 3600 mg dose Patients will receive Dalcetrapib 3600 mg for 10 days |
Drug: Dalcetrapib
Dalcetrapib 300 mg Film-Coated Tablets
|
| Placebo Comparator: Placebo tablets Patients will receive Placebo for 10 days |
Other: Placebo
Placebo Tablets
|
Outcome Measures
Primary Outcome Measures
- To evaluate the time to sustained clinical resolution of symptoms of COVID-19 [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 or paper based equivalent), except for sense of smell and taste where the score should be 0 over a 72-hour period. The time to resolution will be taken as the time from randomization until the first day of the last 72 hour period where the patient meets the definition of resolution within 28 days. Patients who do not meet the definition of resolution 28 days after randomization will be considered not resolved.
Secondary Outcome Measures
- Time to Complete Clinical Resolution [28 days]
Time to complete clinical resolution is defined as occurring when all Coronavirus Disease of 2019 (COVID-19) related symptoms have resolved to a score of 0 over a 72-hour period (as documented using an electronic patient-reported outcome [ePRO] instrument or paper based equivalent). The time to resolution will be taken as the time from randomization until the first day of the last 72 hour period where the patient meets the definition of resolution within 28 days. Patients who do not meet the definition of resolution 28 days after randomization will be considered not resolved.
- Change from Baseline in Coronavirus Disease of 2019 (COVID-19) Symptom Severity Score [Screening (Day -2 to Day -1) up to 28 days]
COVID-19 total symptom severity score will be 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 (N, mean, standard error, confidence interval (CI)). A Mixed-Effect Model Repeated Measure (MMRM) will be performed to analyze the average difference between treatment groups over 28 days and at the designated assessment days. The scale is "Assessment of 14 Common COVID-19-Related Symptoms: Items and Response" from Table 1 in 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". 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) [Screening (Day -2 to Day -1), Days 1, 3, 5, 10, and 28]
The number and percentage of patients for each WHO clinical outcome score will be summarized. An ordinal logistic regression analysis for the specified time points will be presented as odds ratio, with associated 95% confidence interval (CI) and p-value. 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.
- Rate of Hospitalization Through Day 28 [Day 1 to Day 28]
The analysis of this endpoint will be performed on the intention-to-treat (ITT) population. The number and percentage of patients who were hospitalized and reason for hospitalized will be presented. The percentage of patients who were hospitalized will be compared using a logistic regression analysis for specified time points. The results will be presented as odds ratios, with associated 95% confidence intervals (CIs) and p-value.
- Rate of Progression to Oxygen Therapy Through Day 28 [Day 1 to Day 28]
The analysis of this endpoint will be performed on the intention-to-treat (ITT) population. The number and percentage of patients who progress to oxygen therapy and type of oxygen therapy will be presented. The percentage of patients who had progressed to oxygen therapy will be compared using a logistic regression analysis for specified time points. The results will be presented as odds ratios, with associated 95% confidence intervals (CIs) and p-value.
- Duration of Hospitalization [Day 1 thru to Day 28]
The duration of hospitalization will be performed on the intention-to-treat (ITT) population. Duration of hospitalization will be summarized by treatment group using descriptive statistics (N, mean, median, standard deviation, standard error, confidence interval (CI), minimum, and maximum). Linear regression will be performed to analyze the difference between treatment groups. The results will be presented as mean treatment difference with associated 95% confidence interval (CI) and p-value.
- Mortality Rate [Day 1 to Day 28]
The analysis of this endpoint will be performed on the intention-to-treat (ITT) population. The number and percentage of patients who died and reason for death will be presented. The percentage of patients who died will be compared using a logistic regression analysis for specified time points. The results will be presented as odds ratios, with associated 95% confidence intervals (CIs) and p-values.
- Time to Viral Clearance Based on polymerase chain reaction (PCR) Test for Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) [Day 1 to Day 28]
The time to viral clearance based on polymerase chain reaction (PCR) test for Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) will be performed on the intention-to-treat (ITT) population. Time to viral clearance will be summarized by treatment group using Kaplan-Meier methods. Median and associated 95% confidence interval (CI), 25-75 percentiles, and minimum and maximum values will be presented. The number and percentage of patients who do not show virus, show virus, and patients censored will be presented.
- Change from Baseline in log10 Viral Load [Screening/Baseline (Day -2 to Day -1), Day 1, Day 3, Day 5, Day 7, Day 10, and Day 28]
The change from baseline in log10 viral load will be assessed at specified time points by a Mixed-Effect Model Repeated Measure (MMRM). Patients who have achieved a level below the limit of detection will be included in the analysis at half the lower limit of detection. For this endpoint, Last Observation Carried Forward (LOCF) will be used to impute values for all patients. The treatment effect for the difference at each time point, and the average slope up to each time point for each treatment group will be presented along with a 95% confidence interval (CI).
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institut de Cardiologie de Montréal | Montréal | Quebec | Canada | H1T 1C8 |
Sponsors and Collaborators
- DalCor Pharmaceuticals
- The Montreal Health Innovations Coordinating Center (MHICC)
- Covance
Investigators
- Study Director: David Kallend, DalCor Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Guidance for Industry, Investigators, and Institutional Review Boards: FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency [Internet]. Food and Drug Administration; 2020.
- World Health Organization. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020.
- World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard.
Publications
- Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, Xie X, Jin Z, Peng J, Liu F, Li C, Li Y, Bai F, Wang H, Cheng X, Cen X, Hu S, Yang X, Wang J, Liu X, Xiao G, Jiang H, Rao Z, Zhang LK, Xu Y, Yang H, Liu H. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020 Jun 19;368(6497):1331-1335. doi: 10.1126/science.abb4489. Epub 2020 Apr 22.
- Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Holme IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJ, Mundl H, Nicholls SJ, Shah PK, Tardif JC, Wright RS; dal-OUTCOMES Investigators. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Nov 29;367(22):2089-99. doi: 10.1056/NEJMoa1206797. Epub 2012 Nov 5.
- U.S. Department of Health and Human Services, Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. February 4, 2020.
- DAL-401