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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04676867
Recruitment Status : Active, not recruiting
First Posted : December 21, 2020
Last Update Posted : April 23, 2021
Sponsor:
Collaborators:
The Montreal Health Innovations Coordinating Center (MHICC)
Covance
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Covid19 Drug: Dalcetrapib Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 227 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a double blind study.
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-controlled, Phase 2a Proof-of-concept Trial of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19
Actual Study Start Date : January 11, 2021
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

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




Primary Outcome Measures :
  1. To evaluate the time to sustained clinical resolution of symptoms of COVID-19 [ 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 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 :
  1. Time to Complete Clinical Resolution [ Time Frame: 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.

  2. Change from Baseline in Coronavirus Disease of 2019 (COVID-19) Symptom Severity Score [ Time Frame: 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.


  3. Scoring of World Health Organization (WHO) Clinical Outcome Scale (9-point Scale) [ Time Frame: 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.


  4. Rate of Hospitalization Through Day 28 [ Time Frame: 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.

  5. Rate of Progression to Oxygen Therapy Through Day 28 [ Time Frame: 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.

  6. Duration of Hospitalization [ Time Frame: 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.

  7. Mortality Rate [ Time Frame: 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.

  8. Time to Viral Clearance Based on polymerase chain reaction (PCR) Test for Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) [ Time Frame: 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.

  9. Change from Baseline in log10 Viral Load [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04676867


Locations
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Canada, Quebec
Institut de Cardiologie de Montréal
Montréal, Quebec, Canada, H1T 1C8
Sponsors and Collaborators
DalCor Pharmaceuticals
The Montreal Health Innovations Coordinating Center (MHICC)
Covance
Investigators
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Study Director: David Kallend DalCor Pharmaceuticals
Additional Information:
Publications:
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Responsible Party: DalCor Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04676867    
Other Study ID Numbers: DAL-401
First Posted: December 21, 2020    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by DalCor Pharmaceuticals:
COVID-19
Coronavirus disease
Dalcetrapib
Additional relevant MeSH terms:
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Dalcetrapib
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents