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

• ClinicalTrials.gov Identifier: NCT04676867
• Recruitment Status: Recruiting
• First Posted: December 21, 2020
• Last Update Posted: January 19, 2021
• Sponsor: DalCor Pharmaceuticals
• Collaborators: The Montreal Health Innovations Coordinating Center (MHICC); Covance
• Information provided by (Responsible Party): DalCor Pharmaceuticals

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
Covid19	Drug: Dalcetrapib; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 208 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: February 2021
• Estimated Study Completion Date: March 2021

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 :

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), 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.

Eligibility Criteria

• 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 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.

Contacts and Locations

Contacts

Contact: David Kallend; +41 79 174 1830; dkallend@dalcorpharma.com

Contact: Marianne Rufiange; 514-461-1300 ext 2036; Marianne.Rufiange@mhicc.org

Locations

Canada, Quebec

Institut de Cardiologie de Montréal; Recruiting

Montréal, Quebec, Canada, H1T 1C8

Contact: Jean C. Gregoire

Principal Investigator: Jean C. Gregoire

Sponsors and Collaborators

DalCor Pharmaceuticals

The Montreal Health Innovations Coordinating Center (MHICC)

Covance

Investigators

• Study Director: David Kallend; DalCor Pharmaceuticals

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:

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.

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.

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.

• Responsible Party: DalCor Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04676867
• Other Study ID Numbers: DAL-401
• First Posted: December 21, 2020
• Last Update Posted: January 19, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Dalcetrapib; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents