Clinical trial NCT04676867: Effect of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19
Official title: A Double-blind, Placebo-controlled, Phase 2a Proof-of-concept Trial of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: COVID-19
Coronavirus disease
Dalcetrapib
Lead sponsor: DalCor Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Montreal Health Innovations Coordinating Center (MHICC)
name: Covance
First posted: 2020-12-21
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
measure: Change From Baseline in log10 Viral Load (Saliva)
timeFrame: Screening/Baseline (Day -2 to Day -1), Day 3, Day 5, Day 10, and Day 28/End of Study (EOS)
measure: Change From Baseline in log10 Viral Load (Nasal Swab)
timeFrame: Screening/Baseline (Day -2 to Day -1), Day 3, Day 5, Day 10, and Day 28/End of Study (EOS)
measure: Time to Sustained Complete Clinical Resolution of Symptoms in Subjects With Confirmed, Mild to Moderate, Symptomatic COVID-19 Treatment With Dalcetrapib
timeFrame: 28 days
measure: Viral Clearance Using Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) Polymerase Chain Reaction (PCR)
timeFrame: Day 1 to Day 28
measure: 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
timeFrame: 28 days
measure: Time to Complete Clinical Resolution
timeFrame: 28 days
measure: Change From Baseline in Coronavirus Disease of 2019 (COVID-19) Total Symptom Severity Score Collected at All Time Points
timeFrame: 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)
measure: 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
timeFrame: Screening (Day -2 to Day -1), Days 1, 3, 5, End of Treatment (Day 10), Follow-Up Visit (Day 14), and Day 28
measure: Rate of Hospitalization Through Day 28
timeFrame: Day 1 to Day 28
measure: Rate of Progression to Oxygen Therapy Through Day 28
timeFrame: Day 1 to Day 28
measure: Type of Oxygen Therapy Received Through Day 28
timeFrame: Day 1 to Day 28
measure: Duration of Hospitalization
timeFrame: Day 1 through Day 28
measure: Mortality Rate by Day 28
timeFrame: Day 1 to Day 28
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Institut de Cardiologie de Montréal
state: Quebec
Study officials:
affiliation: DalCor Pharmaceuticals
name: David Kallend
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.