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

• ClinicalTrials.gov Identifier: NCT04536090
• Recruitment Status: Not yet recruiting
• First Posted: September 2, 2020
• Last Update Posted: August 23, 2021
• Sponsor: Institut de Recherches Cliniques de Montreal
• Collaborators: Pharmascience Inc.; SCiAN Services, Inc.; Quercis Pharma AG
• Information provided by (Responsible Party): Institut de Recherches Cliniques de Montreal

Tracking Information

• First Submitted Date: August 31, 2020
• First Posted Date: September 2, 2020
• Last Update Posted Date: August 23, 2021
• Estimated Study Start Date: January 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2020)

Disease Progression [ Time Frame: 28 days ]

Disease progression is defined as WHO Clinical Progression Scale ≥6, at any time between Day 1 and Day 28

Original Primary Outcome Measures (submitted: September 1, 2020)

• Changes in viral load from baseline to end of treatment - Mean viral load [ Time Frame: 29 days ]
  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 [ Time Frame: 29 days ]
  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 profiles of viral load [ Time Frame: 29 days ]
  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 to viral negativity [ Time Frame: 29 days ]
  Viral load of SARS-CoV-2 RNA (# of viral copies) assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR)

Current Secondary Outcome Measures (submitted: October 23, 2020)

• Changes in viral load from baseline to end of treatment - Mean viral load [ Time Frame: 28 days ]
  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 [ Time Frame: 28 days ]
  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 [ Time Frame: 28 days ]
  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 [ Time Frame: 28 days ]
  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 [ Time Frame: 28 days ]
  Disease recovery is defined as WHO Clinical Progression Scale score of ≤2
• Change in WHO Clinical Progression Scale score [ Time Frame: 28 days ]
  Change in score from baseline to day 28
• Incidence of all-cause mortality [ Time Frame: 30 days ]
  All-cause mortality calculated at Day 30
• Progression to supplementary oxygen requirement [ Time Frame: 14 days ]
  If the patient required supplementary oxygen during hospitalization
• Incidence of mechanical ventilation [ Time Frame: 14 days ]
  If the patient required mechanical ventilation during hospitalization
• Incidence of ICU admission [ Time Frame: 14 days ]
  If the patient was admitted to ICU
• Time to hospital discharge [ Time Frame: 29 days ]
  Length of time in hospital prior to being discharged
• Changes in serum C reactive protein levels (CRP) [ Time Frame: 29 days ]
  Changes in serum CRP levels
• Changes in D-dimer levels [ Time Frame: 29 days ]
  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 [ Time Frame: 29 days ]
  Changes in sLDLR expression, and PCSK9 and sACE2 levels
• Changes in LDL-cholesterol [ Time Frame: 29 days ]
  Changes in LDL-cholesterol
• Changes in creatinine [ Time Frame: 29 days ]
  Changes in creatinine
• Changes in liver enzymes [ Time Frame: 29 days ]
  Changes in liver enzymes

Original Secondary Outcome Measures (submitted: September 1, 2020)

• Time to clinical recovery [ Time Frame: 29 days ]
  Clinical recovery is defined as:

  1. Fever </= 36.6 degrees C
  2. Respiratory rate </= 24/minute on room air
  3. Oxygen saturation >94% on room air
  4. Cough mild or absent
• All-cause mortality [ Time Frame: 29 days ]
  All-cause mortality calculated at Day 29
• Progression to supplementary oxygen requirement [ Time Frame: 14 days ]
  If the patient required supplementary oxygen during hospitalization
• Incidence of mechanical ventilation [ Time Frame: 14 days ]
  If the patient required mechanical ventilation during hospitalization
• Incidence of ICU admission [ Time Frame: 14 days ]
  If the patient was admitted to ICU
• Time to hospital discharge [ Time Frame: 29 days ]
  Length of time in hospital prior to being discharged
• Changes in serum C reactive protein levels (CRP) [ Time Frame: 29 days ]
  Changes in serum CRP levels
• Changes in D-dimer levels [ Time Frame: 29 days ]
  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 [ Time Frame: 29 days ]
  Changes in sLDLR expression, and PCSK9 and sACE2 levels
• Changes in LDL-cholesterol [ Time Frame: 29 days ]
  Changes in LDL-cholesterol
• Changes in creatinine [ Time Frame: 29 days ]
  Changes in creatinine
• Changes in liver enzymes [ Time Frame: 29 days ]
  Changes in liver enzymes

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

Drug: Isoquercetin (IQC-950AN)

Isoquercetin will be administered by mouth twice daily for 28 days

Other Name: IQC-950AN

Study Arms

• 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)
  Intervention: Drug: Isoquercetin (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.

• 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.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 1, 2020): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michel Chrétien, FRS MD FRCP©; 1-833-705-0648; michel.chretien@ircm.qc.ca

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04536090
• Other Study ID Numbers: IRCM-IQC-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Institut de Recherches Cliniques de Montreal
• Original Responsible Party: Same as current
• Current Study Sponsor: Institut de Recherches Cliniques de Montreal
• Original Study Sponsor: Same as current

Collaborators

• Pharmascience Inc.
• SCiAN Services, Inc.
• Quercis Pharma AG

Investigators

• Study Director: Michel Chrétien, FRS MD FRCP©; Montreal Clinical Research Institute

• PRS Account: Institut de Recherches Cliniques de Montreal
• Verification Date: August 2021