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

NCT04676867 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DAL-401
• Study Type: interventional
• Target: 227
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19

Keywords

COVID-19; Coronavirus disease; Dalcetrapib

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  28 days

Secondary Outcomes (13)

• 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)

• 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)

• Time to Sustained Complete Clinical Resolution of Symptoms in Subjects With Confirmed, Mild to Moderate, Symptomatic COVID-19 Treatment With Dalcetrapib

  28 days

• Viral Clearance Using Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) Polymerase Chain Reaction (PCR)

  Day 1 to Day 28

• 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

Study Arms (4)

900 mg dose

ACTIVE COMPARATOR

Patients will receive Dalcetrapib 900 mg for 10 days

Drug: Dalcetrapib

1800 mg dose

ACTIVE COMPARATOR

Patients will receive Dalcetrapib 1800 mg for 10 days

Drug: Dalcetrapib

3600 mg dose

ACTIVE COMPARATOR

Patients will receive Dalcetrapib 3600 mg for 10 days

Drug: Dalcetrapib

Placebo tablets

PLACEBO COMPARATOR

Patients will receive Placebo for 10 days

Other: Placebo

Interventions

Dalcetrapib DRUG

Dalcetrapib 300 mg Film-Coated Tablets

1800 mg dose; 3600 mg dose; 900 mg dose

Placebo OTHER

Placebo Tablets

Placebo tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• DalCor Pharmaceuticals: lead
• The Montreal Health Innovations Coordinating Center (MHICC): collaborator
• Covance: collaborator

Study Sites (1)

Institut de Cardiologie de Montréal

Montreal, Quebec, H1T 1C8, Canada

Location

Related Publications (3)

• 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.

  BACKGROUND

• 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.

  PMID: 23126252 BACKGROUND

• 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.

  PMID: 32321856 BACKGROUND

Related Links

• World Health Organization. WHO Coronavirus Disease (COVID-19) Dashboard.

MeSH Terms

Conditions

COVID-19

Interventions

dalcetrapib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Small sample size, remote study, and patients were self-sampling for the polymerase chain reaction (PCR) testing albeit under supervision.

Results Point of Contact

• Title: David Kallend
• Organization: DalCor Pharmaceuticals

dkallend@dalcorpharma.com

+1 514-508-5099

Study Officials

• David Kallend

  DalCor Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, double blind, multicenter, Phase 2a proof-of-concept study in outpatients with confirmed, mild to moderate, symptomatic COVID-19.

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 21, 2020
• Study Start: January 11, 2021
• Primary Completion: May 17, 2021
• Study Completion: May 17, 2021
• Last Updated: December 7, 2022
• Results First Posted: December 7, 2022

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)