<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04474626</url>
  </required_header>
  <id_info>
    <org_study_id>20-087</org_study_id>
    <nct_id>NCT04474626</nct_id>
  </id_info>
  <brief_title>Isoquercetin in Sickle Cell Anemia</brief_title>
  <official_title>Single-arm Phase 2 Study of Oral Isoquercetin in Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jeffrey Zwicker, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quercegen Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is being done to assess the safety and effectiveness of isoquercetin to&#xD;
      reduce levels of soluble P-Selectin in patients with sickle cell disease. Isoquercetin is a&#xD;
      naturally occurring flavonoid-or vitamin. You will find quercetin and isoquercetin in fruits&#xD;
      and vegetables.&#xD;
&#xD;
      The names of the study drug involved in this study are/is:&#xD;
&#xD;
      - Isoquercetin&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-arm phase 2 study in adults with Sickle Cell Disease (SCD) to assess the&#xD;
      effect of oral isoquercetin on biomarkers of endothelial and platelet activation,&#xD;
      inflammation and ongoing blood coagulation.&#xD;
&#xD;
        -  The research study procedures include screening for eligibility and study treatment&#xD;
           including evaluations and follow up visits.&#xD;
&#xD;
             -  The names of the study drug involved in this study are/is: Isoquercetin&#xD;
&#xD;
             -  Participants will receive study treatment for 1 year and will be followed for 30&#xD;
                days after the last dose.&#xD;
&#xD;
        -  This research study is a Phase II clinical trial. Phase II clinical trials test the&#xD;
           safety and effectiveness of an investigational drug to learn whether the drug works in&#xD;
           treating a specific disease. &quot;Investigational&quot; means that the drug is being studied.&#xD;
&#xD;
        -  The U.S. Food and Drug Administration (FDA) has not approved isoquercetin as a treatment&#xD;
           for any disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Trial did not activate&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in sP Selectin levels with isoquercetin</measure>
    <time_frame>baseline to 28 Days</time_frame>
    <description>Comparisons between baseline and follow-up measurements (i.e. change in sP-Selectin), will be performed using a two-tailed, paired t-test analyses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet dependent thrombin generation (coagulation)</measure>
    <time_frame>baseline to 1 year</time_frame>
    <description>Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>sE-selectin (adhesion)-Biomarker</measure>
    <time_frame>baseline to 1 year</time_frame>
    <description>Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive protein CRP</measure>
    <time_frame>baseline to 1 year</time_frame>
    <description>Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events</measure>
    <time_frame>start of study treatment up to 13 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Sickle Cell Disease</condition>
  <condition>Sickle Cell-Beta0-Thalassemia</condition>
  <arm_group>
    <arm_group_label>ISOQUERCETIN</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits&#xD;
- ISOQUERCETIN: Oral Study Drug, 1 time per day, per predetermined dosed per 28 treatment cycle.&#xD;
This will continue for up to 337 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoquercetin</intervention_name>
    <description>Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.</description>
    <arm_group_label>ISOQUERCETIN</arm_group_label>
    <other_name>IQC-950AN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eligible subjects require an established diagnosis of sickle cell disease/homozygous&#xD;
             hemoglobin S (SCD-SS) or sickle cell disease hemoglobin β0-thalassemia (SCD-Sβ0-thal).&#xD;
&#xD;
          -  Patients on other therapy including hydroxyurea will be included.&#xD;
&#xD;
          -  Age 18-50 years.&#xD;
&#xD;
          -  Participants must have preserved organ and marrow function as defined below:&#xD;
&#xD;
               -  leukocytes ≥2,000/mcL&#xD;
&#xD;
               -  platelets ≥75,000/mcL&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal&#xD;
&#xD;
               -  Estimated creatinine clearance ≥45 mL/min/1.73 m2 for participants with&#xD;
                  creatinine levels above institutional normal.&#xD;
&#xD;
          -  Subjects with no evidence of worsening over the last 4 weeks (e.g. any acute&#xD;
             complication of SCD including but not limited to VOC, acute chest syndrome and stroke,&#xD;
             that required unscheduled medical attention or intervention) as determined by the&#xD;
             investigator will be included.&#xD;
&#xD;
          -  Patients on anticoagulation therapy will be excluded.&#xD;
&#xD;
          -  The effects of isoquercetin on the developing human fetus are unknown. For this&#xD;
             reason, women of child-bearing potential and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
             entry and for the duration of study participation. Should a woman become pregnant or&#xD;
             suspect she is pregnant while she or her partner is participating in this study, she&#xD;
             should inform her treating physician immediately. Men treated or enrolled on this&#xD;
             protocol must also agree to use adequate contraception prior to the study, for the&#xD;
             duration of study participation, and 4 months after completion of isoquercetin&#xD;
             administration.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Please ensure exclusion criteria are clearly worded to describe participants who will&#xD;
             not be eligible.&#xD;
&#xD;
          -  Participants may not be concurrently receiving any other study agents.&#xD;
&#xD;
          -  Subjects with no evidence of worsening over the last 1 month (e.g. any acute&#xD;
             complication of SCD including but not limited to VOC, acute chest syndrome and stroke,&#xD;
             that required unscheduled medical attention or intervention) as determined by the&#xD;
             investigator will be included.&#xD;
&#xD;
          -  Familial bleeding diathesis.&#xD;
&#xD;
          -  Known diagnosis of disseminated intravascular coagulation.&#xD;
&#xD;
          -  Currently receiving anticoagulant therapy.&#xD;
&#xD;
          -  Currently using daily use of aspirin (&gt;81mg daily), Clopidogrel (Plavix), cilostazol&#xD;
             (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days)&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to isoquercetin.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including but not limited to ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia,&#xD;
             or psychiatric illness/social situations that would limit study compliance.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor&#xD;
             with the potential for teratogenic or abortifacient effects. Because there is an&#xD;
             unknown but potential risk of adverse events in nursing infants secondary to treatment&#xD;
             of the mother with isoquercetin, breastfeeding should be discontinued if the mother is&#xD;
             treated with isoquercetin. These potential risks may also apply to other agents used&#xD;
             in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey Zwicker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>January 7, 2021</last_update_submitted>
  <last_update_submitted_qc>January 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Jeffrey Zwicker, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Sickle Cell-Beta0-Thalassemia</keyword>
  <keyword>isoquercetin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04474626
org study id: 20-087
nct id: NCT04474626
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in sP Selectin levels with isoquercetin
time frame: baseline to 28 Days
description: Comparisons between baseline and follow-up measurements (i.e. change in sP-Selectin), will be performed using a two-tailed, paired t-test analyses.
measure: Platelet dependent thrombin generation (coagulation)
time frame: baseline to 1 year
description: Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
measure: sE-selectin (adhesion)-Biomarker
time frame: baseline to 1 year
description: Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
measure: C-reactive protein CRP
time frame: baseline to 1 year
description: Laboratory values at baseline and subsequent monthly follow-up time points will be modeled using linear mixed effects regression with an autoregressive covariance structure.
measure: Number of Participants With Treatment-Related Adverse Events
time frame: start of study treatment up to 13 months
description: 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.
arm group label: ISOQUERCETIN
arm group type: Experimental
description: 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 type: Drug
intervention name: Isoquercetin
description: Oral, 1 time per day, per predetermined dosed per 28 treatment cycle.
arm group label: ISOQUERCETIN
other name: IQC-950AN
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeffrey Zwicker, MD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Jeffrey Zwicker, MD
investigator title: Principal Investigator
mesh term: Anemia, Sickle Cell
mesh term: Thalassemia
sharing ipd: Yes
ipd 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.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu