Study of Isoquercetin (IQC-950AN) Plus Standard of Care Versus Standard of Care Only for the Treatment of COVID-19

An Open-Label Randomized Study of Isoquercetin (IQC-950AN) Plus Standard of Care Versus Standard of Care Only for the Treatment of 2019 Novel Coronavirus Disease (COVID-19)

This is an open-label, randomized, multi-centre study where hospitalized subjects will be randomized in a 2:1 ratio to receive Isoquercetin (IQC-950AN) in addition to standard of care or standard of care only for 28 days following confirmation of a COVID-19 infection.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Isoquercetin (IQC-950AN)

Detailed Description

The primary purpose of this randomized study will be to evaluate the effect of Isoquercetin (IQC-950AN) treatment on disease progression (defined as ≥ 6 on the World Health Organization (WHO) clinical progression scale) when given to subjects with confirmed COVID-19 in addition to standard of care. The secondary purpose of this study is to evaluate the effect of Isoquercetin (IQC-950AN) treatment on the reduction of severe acute respiratory coronavirus 2 (SARS-CoV-2) viral titers in these subjects and their recovery. In addition, certain parameters which may help elucidate the mechanism of action (sLDLR, PCSK9, sACE2, D-dimers and CRP) will be followed. The safety of Isoquercetin (IQC-950AN) will be evaluated at each visit. Subjects will be randomized to receive treatment for 28 days and then will return 30 days following the discontinuation of treatment for a final safety visit.

The results of this study will be used to design an adequately powered randomized controlled pivotal study to evaluate the efficacy and safety of Isoquercetin (IQC-950AN) in all or a subset of subjects with confirmed COVID-19.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michel Chrétien, FRS MD FRCP©; Phone Number: 1-833-705-0648; Email: michel.chretien@ircm.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must exhibit symptoms of COVID-19 disease at screening;
2. Patients must be 18 years of age or older, of either gender;
3. Patients must have a documented SARS-CoV-2 RNA-positive test virus within 3 days prior to randomization;
4. Patients must be admitted (or under observation to be admitted) to a controlled facility or hospital to receive standard-of-care for COVID-19 disease;
5. Patient's health status must be 3 (if hospitalized for comorbidities), 4, or 5 on the WHO clinical progression scale defined as hospitalized moderate disease (no oxygen therapy or oxygen by mask or nasal prongs);
6. If female, must be either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who are capable of conception, must be: practicing a highly effective method of birth control during the study and through 30 days after the last dose of the study medication.
7. Patients must have the ability to understand and give informed consent, which can be verbal with a witness, according to local requirements;
8. Patients deemed capable of adequate compliance including attending scheduled visits for the duration of the study;
9. Patients must be able to swallow the study drug capsules

Exclusion Criteria:

1. Patients with a history of allergy or anaphylaxis to ingredients in Isoquercetin (IQC-950AN) including known intolerance of niacin or ascorbic acid or known glucose-6-phosphate dehydrogenase (G6PD) deficiency;
2. Patients with known chronic kidney disease with estimated creatinine clearance < 50 mL/minute or need for dialysis;
3. Patients receiving an intensified dose regimen of low molecular weight heparin (LMWH) or unfractionated heparin (defined as doses of LMWH or unfractionated heparin greater than those approved for thromboprophylaxis) or dual antiplatelet therapy;
4. Patients who are severely hypotensive defined as needing hemodynamic pressors to maintain blood pressure;
5. Patients with moderate or severe thrombocytopenia (platelet count <100 × 10⁹/L);
6. Patients who are breast-feeding an infant or child;
7. Patients who are pregnant or unwilling to use an appropriate form of contraception, except for heterosexual celibacy
8. Any other condition that, in the opinion of the investigator, may adversely affect the patient's ability to complete this study or its measures, or pose a significant risk to the patient;
9. Any reason the investigator suspects that data collected from this patient would be incomplete or of poor quality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isoquercetin (IQC-950AN); 1000 mg Isoquercetin b.i.d. on day 1, then 500 mg Isoquercetin b.i.d. for 27 more days, plus standard of care (as defined below)	Drug: Isoquercetin (IQC-950AN); Isoquercetin will be administered by mouth twice daily for 28 days; Other Names: IQC-950AN
No Intervention: Standard of care; This arm will receive standard of care based on national guidelines. This may change as new information regarding best practice emerges.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Progression	Disease progression is defined as WHO Clinical Progression Scale ≥6, at any time between Day 1 and Day 28	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in viral load from baseline to end of treatment - Mean viral load	Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)	28 days
Changes in viral load from baseline to end of treatment - Area under the viral load vs. time profiles	Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)	28 days
Changes in viral load from baseline to end of treatment - Time profile of viral load	Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)	28 days
Changes in viral load from baseline to end of treatment - Percentage of patients that are viral negative	Defined as below the level of quantitation of the assay (qRT-PCR). Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)	28 days
Disease Recovery	Disease recovery is defined as WHO Clinical Progression Scale score of ≤2	28 days
Change in WHO Clinical Progression Scale score	Change in score from baseline to day 28	28 days
Incidence of all-cause mortality	All-cause mortality calculated at Day 30	30 days
Progression to supplementary oxygen requirement	If the patient required supplementary oxygen during hospitalization	14 days
Incidence of mechanical ventilation	If the patient required mechanical ventilation during hospitalization	14 days
Incidence of ICU admission	If the patient was admitted to ICU	14 days
Time to hospital discharge	Length of time in hospital prior to being discharged	29 days
Changes in serum C reactive protein levels (CRP)	Changes in serum CRP levels	29 days
Changes in D-dimer levels	Changes in D-dimer levels	29 days
Changes in soluble low-density lipoprotein receptor (sLDLR) expression and proprotein convertase subtilisin/kexin type 9 (PCSK9) and soluble angiotensin converting enzyme 2 (sACE2) levels	Changes in sLDLR expression, and PCSK9 and sACE2 levels	29 days
Changes in LDL-cholesterol	Changes in LDL-cholesterol	29 days
Changes in creatinine	Changes in creatinine	29 days
Changes in liver enzymes	Changes in liver enzymes	29 days

Collaborators and Investigators

• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: Pharmascience Inc.; SCiAN Services, Inc.; Quercis Pharma AG
• Investigators: Study Director: Michel Chrétien, FRS MD FRCP©, Montreal Clinical Research Institute

Publications and helpful links

General Publications

• WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. doi: 10.1016/S1473-3099(20)30483-7. Epub 2020 Jun 12. Erratum In: Lancet Infect Dis. 2020 Oct;20(10):e250.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Antiviral Agents; Quercetin; Isoquercetin
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: IRCM-IQC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No