Isoquercetin in Sickle Cell Anemia

• ClinicalTrials.gov Identifier: NCT04474626
• Recruitment Status: Withdrawn
• First Posted: July 17, 2020
• Last Update Posted: January 11, 2021
• Sponsor: Jeffrey Zwicker, MD
• Collaborator: Quercegen Pharmaceuticals
• Information provided by (Responsible Party): Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center

Tracking Information

• First Submitted Date: July 6, 2020
• First Posted Date: July 17, 2020
• Last Update Posted Date: January 11, 2021
• Estimated Study Start Date: December 2020
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2020)

Change in sP Selectin levels with isoquercetin [ Time Frame: baseline to 28 Days ]

Comparisons between baseline and follow-up measurements (i.e. change in sP-Selectin), will be performed using a two-tailed, paired t-test analyses.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 13, 2020)

• Platelet dependent thrombin generation (coagulation) [ Time Frame: baseline to 1 year ]
  Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
• sE-selectin (adhesion)-Biomarker [ Time Frame: baseline to 1 year ]
  Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
• C-reactive protein CRP [ Time Frame: baseline to 1 year ]
  Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
• Number of Participants With Treatment-Related Adverse Events [ Time Frame: start of study treatment up to 13 months ]
  Sickle cell events such as SCPC, uncomplicated pain crisis, hospitalizations, emergency room visits, transfusions, acute chest syndrome and transfusion support will be summarized as annualized numbers. Statistical comparisons will be made for each patient relative to the number from the previous year using a Wilcoxon rank-sum test.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Isoquercetin in Sickle Cell Anemia
• Official Title: Single-arm Phase 2 Study of Oral Isoquercetin in Sickle Cell Disease

Brief Summary

This research study is being done to assess the safety and effectiveness of isoquercetin to reduce levels of soluble P-Selectin in patients with sickle cell disease. Isoquercetin is a naturally occurring flavonoid-or vitamin. You will find quercetin and isoquercetin in fruits and vegetables.

The names of the study drug involved in this study are/is:

- Isoquercetin

Detailed Description

This is a single-arm phase 2 study in adults with Sickle Cell Disease (SCD) to assess the effect of oral isoquercetin on biomarkers of endothelial and platelet activation, inflammation and ongoing blood coagulation.

• The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

  • The names of the study drug involved in this study are/is: Isoquercetin
  • Participants will receive study treatment for 1 year and will be followed for 30 days after the last dose.
• This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
• The U.S. Food and Drug Administration (FDA) has not approved isoquercetin as a treatment for any disease.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sickle Cell Disease
• Sickle Cell-Beta0-Thalassemia

Intervention

Drug: Isoquercetin

Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.

Other Name: IQC-950AN

Study Arms

Experimental: ISOQUERCETIN

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits

- ISOQUERCETIN: Oral Study Drug, 1 time per day, per predetermined dosed per 28 treatment cycle.

This will continue for up to 337 days.

Intervention: Drug: Isoquercetin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: January 7, 2021): 0
• Original Estimated Enrollment (submitted: July 13, 2020): 20
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eligible subjects require an established diagnosis of sickle cell disease/homozygous hemoglobin S (SCD-SS) or sickle cell disease hemoglobin β0-thalassemia (SCD-Sβ0-thal).
• Patients on other therapy including hydroxyurea will be included.
• Age 18-50 years.

• Participants must have preserved organ and marrow function as defined below:

  • leukocytes ≥2,000/mcL
  • platelets ≥75,000/mcL
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
  • Estimated creatinine clearance ≥45 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• Subjects with no evidence of worsening over the last 4 weeks (e.g. any acute complication of SCD including but not limited to VOC, acute chest syndrome and stroke, that required unscheduled medical attention or intervention) as determined by the investigator will be included.
• Patients on anticoagulation therapy will be excluded.
• The effects of isoquercetin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of isoquercetin administration.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Please ensure exclusion criteria are clearly worded to describe participants who will not be eligible.
• Participants may not be concurrently receiving any other study agents.
• Subjects with no evidence of worsening over the last 1 month (e.g. any acute complication of SCD including but not limited to VOC, acute chest syndrome and stroke, that required unscheduled medical attention or intervention) as determined by the investigator will be included.
• Familial bleeding diathesis.
• Known diagnosis of disseminated intravascular coagulation.
• Currently receiving anticoagulant therapy.
• Currently using daily use of aspirin (>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to isoquercetin.
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness/social situations that would limit study compliance.
• Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with isoquercetin. These potential risks may also apply to other agents used in this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT04474626
• Other Study ID Numbers: 20-087
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

• Current Responsible Party: Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Jeffrey Zwicker, MD
• Original Study Sponsor: Same as current
• Collaborators: Quercegen Pharmaceuticals

Investigators

• Principal Investigator: Jeffrey Zwicker, MD; Beth Israel Deaconess Medical Center

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: January 2021