Study of Isoquercetin (IQC-950AN) Plus Standard of Care Versus Standard of Care Only for the Treatment of COVID-19
Primary Purpose
COVID-19
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Isoquercetin (IQC-950AN)
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Isoquercetin, Quercetin, Antiviral Agents
Eligibility Criteria
Inclusion Criteria:
- Patients must exhibit symptoms of COVID-19 disease at screening;
- Patients must be 18 years of age or older, of either gender;
- Patients must have a documented SARS-CoV-2 RNA-positive test virus within 3 days prior to randomization;
- 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;
- 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);
- 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.
- Patients must have the ability to understand and give informed consent, which can be verbal with a witness, according to local requirements;
- Patients deemed capable of adequate compliance including attending scheduled visits for the duration of the study;
- Patients must be able to swallow the study drug capsules
Exclusion Criteria:
- 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;
- Patients with known chronic kidney disease with estimated creatinine clearance < 50 mL/minute or need for dialysis;
- 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;
- Patients who are severely hypotensive defined as needing hemodynamic pressors to maintain blood pressure;
- Patients with moderate or severe thrombocytopenia (platelet count <100 × 10⁹/L);
- Patients who are breast-feeding an infant or child;
- Patients who are pregnant or unwilling to use an appropriate form of contraception, except for heterosexual celibacy
- 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;
- Any reason the investigator suspects that data collected from this patient would be incomplete or of poor quality
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Isoquercetin (IQC-950AN)
Standard of care
Arm Description
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)
This arm will receive standard of care based on national guidelines. This may change as new information regarding best practice emerges.
Outcomes
Primary Outcome Measures
Disease Progression
Disease progression is defined as WHO Clinical Progression Scale ≥6, at any time between Day 1 and Day 28
Secondary Outcome Measures
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)
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)
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)
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)
Disease Recovery
Disease recovery is defined as WHO Clinical Progression Scale score of ≤2
Change in WHO Clinical Progression Scale score
Change in score from baseline to day 28
Incidence of all-cause mortality
All-cause mortality calculated at Day 30
Progression to supplementary oxygen requirement
If the patient required supplementary oxygen during hospitalization
Incidence of mechanical ventilation
If the patient required mechanical ventilation during hospitalization
Incidence of ICU admission
If the patient was admitted to ICU
Time to hospital discharge
Length of time in hospital prior to being discharged
Changes in serum C reactive protein levels (CRP)
Changes in serum CRP levels
Changes in D-dimer levels
Changes in D-dimer levels
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
Changes in LDL-cholesterol
Changes in LDL-cholesterol
Changes in creatinine
Changes in creatinine
Changes in liver enzymes
Changes in liver enzymes
Full Information
NCT ID
NCT04536090
First Posted
August 31, 2020
Last Updated
August 20, 2021
Sponsor
Institut de Recherches Cliniques de Montreal
Collaborators
Pharmascience Inc., SCiAN Services, Inc., Quercis Pharma AG
1. Study Identification
Unique Protocol Identification Number
NCT04536090
Brief Title
Study of Isoquercetin (IQC-950AN) Plus Standard of Care Versus Standard of Care Only for the Treatment of COVID-19
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 2022 (Anticipated)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
June 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Recherches Cliniques de Montreal
Collaborators
Pharmascience Inc., SCiAN Services, Inc., Quercis Pharma AG
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Isoquercetin, Quercetin, Antiviral Agents
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Isoquercetin (IQC-950AN)
Arm Type
Experimental
Arm Description
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)
Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
This arm will receive standard of care based on national guidelines. This may change as new information regarding best practice emerges.
Intervention Type
Drug
Intervention Name(s)
Isoquercetin (IQC-950AN)
Other Intervention Name(s)
IQC-950AN
Intervention Description
Isoquercetin will be administered by mouth twice daily for 28 days
Primary Outcome Measure Information:
Title
Disease Progression
Description
Disease progression is defined as WHO Clinical Progression Scale ≥6, at any time between Day 1 and Day 28
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Changes in viral load from baseline to end of treatment - Mean viral load
Description
Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
Time Frame
28 days
Title
Changes in viral load from baseline to end of treatment - Area under the viral load vs. time profiles
Description
Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
Time Frame
28 days
Title
Changes in viral load from baseline to end of treatment - Time profile of viral load
Description
Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
Time Frame
28 days
Title
Changes in viral load from baseline to end of treatment - Percentage of patients that are viral negative
Description
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)
Time Frame
28 days
Title
Disease Recovery
Description
Disease recovery is defined as WHO Clinical Progression Scale score of ≤2
Time Frame
28 days
Title
Change in WHO Clinical Progression Scale score
Description
Change in score from baseline to day 28
Time Frame
28 days
Title
Incidence of all-cause mortality
Description
All-cause mortality calculated at Day 30
Time Frame
30 days
Title
Progression to supplementary oxygen requirement
Description
If the patient required supplementary oxygen during hospitalization
Time Frame
14 days
Title
Incidence of mechanical ventilation
Description
If the patient required mechanical ventilation during hospitalization
Time Frame
14 days
Title
Incidence of ICU admission
Description
If the patient was admitted to ICU
Time Frame
14 days
Title
Time to hospital discharge
Description
Length of time in hospital prior to being discharged
Time Frame
29 days
Title
Changes in serum C reactive protein levels (CRP)
Description
Changes in serum CRP levels
Time Frame
29 days
Title
Changes in D-dimer levels
Description
Changes in D-dimer levels
Time Frame
29 days
Title
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
Description
Changes in sLDLR expression, and PCSK9 and sACE2 levels
Time Frame
29 days
Title
Changes in LDL-cholesterol
Description
Changes in LDL-cholesterol
Time Frame
29 days
Title
Changes in creatinine
Description
Changes in creatinine
Time Frame
29 days
Title
Changes in liver enzymes
Description
Changes in liver enzymes
Time Frame
29 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must exhibit symptoms of COVID-19 disease at screening;
Patients must be 18 years of age or older, of either gender;
Patients must have a documented SARS-CoV-2 RNA-positive test virus within 3 days prior to randomization;
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;
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);
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.
Patients must have the ability to understand and give informed consent, which can be verbal with a witness, according to local requirements;
Patients deemed capable of adequate compliance including attending scheduled visits for the duration of the study;
Patients must be able to swallow the study drug capsules
Exclusion Criteria:
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;
Patients with known chronic kidney disease with estimated creatinine clearance < 50 mL/minute or need for dialysis;
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;
Patients who are severely hypotensive defined as needing hemodynamic pressors to maintain blood pressure;
Patients with moderate or severe thrombocytopenia (platelet count <100 × 10⁹/L);
Patients who are breast-feeding an infant or child;
Patients who are pregnant or unwilling to use an appropriate form of contraception, except for heterosexual celibacy
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;
Any reason the investigator suspects that data collected from this patient would be incomplete or of poor quality
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michel Chrétien, FRS MD FRCP©
Phone
1-833-705-0648
Email
michel.chretien@ircm.qc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel Chrétien, FRS MD FRCP©
Organizational Affiliation
Montreal Clinical Research Institute
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32539990
Citation
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.
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Study of Isoquercetin (IQC-950AN) Plus Standard of Care Versus Standard of Care Only for the Treatment of COVID-19
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