<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/NCT04503928</url>
  </required_header>
  <id_info>
    <org_study_id>Euphorbia kansui V1</org_study_id>
    <nct_id>NCT04503928</nct_id>
  </id_info>
  <brief_title>Euphorbia Kansui and HIV/AIDS Functional Cure</brief_title>
  <official_title>Euphorbia Kansui in Combination With Antiretroviral Therapy for Eradication of the Latent HIV-1 Reservoir</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Public Health Clinical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai Xinhao Biological Technology Co., Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Public Health Clinical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and bioactivity of Euphorbia kansui,&#xD;
      which has been used in traditional Chinese medicine for the treatment of edema, ascites, and&#xD;
      asthma. The investigators previously reported that effective fractions from the&#xD;
      dichloromethane extracts of the roots of Euphorbia kansui can reactivate latent HIV-1&#xD;
      replication in different latent cells (The 24th China science technology Forum-High level&#xD;
      Forum on HIV cure, December 16-17, 2012, Beijing). Importantly, in resting CD4+ T cells of&#xD;
      HIV-1-infected patients on suppressive antiretroviral therapy (ART), it could effectively&#xD;
      induce ex vivo latent HIV-1 expression. Sera from rats receiving orally administered&#xD;
      effective fractions were able to reactivate latent HIV-1. The investigators also found a&#xD;
      substantially potent ingenol derivative EK-16A, EK-1A, EK-5A, EK-15A from Euphorbia kansui&#xD;
      and proved that it was potent in reversing HIV-1 latency. The investigators' hypothesis is&#xD;
      that Euphorbia kansui Pill will be safe and well-tolerated and at the doses administered,&#xD;
      increase HIV transcription in latently-infected cells among HIV-infected patients on&#xD;
      suppressive antiretroviral therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Every participant will receive oral Euphorbia kansui Pill every day. The dose of Euphorbia&#xD;
      kansui will be 1g each time for 7 consecutive days. All participants will keep their&#xD;
      antiretroviral therapy during this study.&#xD;
&#xD;
      Each step of this study will last for 21 days, involving 7 study visits (Screening,Day 0, 1,&#xD;
      3, 5, 7, 14, 21) for every participant. At the screening visit, participants will give a&#xD;
      medical history and will undergo a physical exam; blood samples will be collected.&#xD;
      Participants will undergo pharmacodynamic sampling which will require that blood be collected&#xD;
      12 hours after kansui Pill administration on Day 1, 3, 5,7. If participants agree, their&#xD;
      blood samples may be stored for future research.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>All participants eligible for study received the same open label drug</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in plasma HIV-1 RNA concentration</measure>
    <time_frame>Measured on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cell-associated HIV-1 RNA</measure>
    <time_frame>on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Measured through 21 days after the first administration of kansui Pill</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in cell-associated total HIV-1 DNA</measure>
    <time_frame>Measured on day 0, 14, 21</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>HIV-1-infection</condition>
  <arm_group>
    <arm_group_label>Experimental: Kansui 1g per day x 7 days</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study participants will be given 1 g of Euphorbia kansui Pill for a total of 7 consecutive daily doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Euphorbia kansui Pill</intervention_name>
    <description>1 g (10 pills) of Euphorbia kansui Pill taken by mouth, once a day for 7 consecutive days.</description>
    <arm_group_label>Experimental: Kansui 1g per day x 7 days</arm_group_label>
    <other_name>kansui</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HIV-1 infection&#xD;
&#xD;
          2. Age ≥18 years; Willingness to give written informed consent.&#xD;
&#xD;
          3. Karnofsky performance status &gt;70.&#xD;
&#xD;
          4. Able, willing to adhere to therapy and adherent to ART.&#xD;
&#xD;
          5. Able, willing to comply with time requirements for study visits and evaluations.&#xD;
&#xD;
          6. On potent combination ART for ≥ 18 months prior to study entry.&#xD;
&#xD;
          7. Able to swallow pills without difficulty.&#xD;
&#xD;
          8. HIV-1 RNA values &lt;50 copies/mL for at least 18 months.&#xD;
&#xD;
          9. CD4 cell count ≥ 500 cells/µl at screening.&#xD;
&#xD;
         10. CD4 T cells isolated in vitro and stimulated with kansui, and the kansui activation&#xD;
             test is positive.&#xD;
&#xD;
         11. All volunteers must agree not to participate in a conception process.&#xD;
&#xD;
         12. Must have adequate organ function as indicated by the following lab values:&#xD;
&#xD;
        Hematological: Absolute Neutrophil Count (ANC) ≥ 1,500/mcL Platelets ≥ 125,000/mcL Hgb ≥ 12&#xD;
        g/dL Coagulation: Prothrombin Time or International Normalized Ratio (INR) ≤ 1.5x upper&#xD;
        limit of normal (ULN) Chemistry: K+ levels Within normal limits Mg++ levels &gt; Lower limits&#xD;
        of normal (LLN) but &lt;1.5 x ULN Glucose Screening serum glucose(fasting/non-fasting) below&#xD;
        120 mg/dl.&#xD;
&#xD;
        Renal: Serum creatinine/calculated creatinine clearance* ≤ 1.3 X ULN OR ≥ 60 mL/min for&#xD;
        participants with creatinine levels &gt; 1.3 X ULN Hepatic: Serum total bilirubin Total&#xD;
        bilirubin &lt; 1.5 times ULN. If total bilirubin is elevated, direct bilirubin will be&#xD;
        measured and the participant will be eligible if the direct bilirubin is &lt; 2 X ULN.&#xD;
&#xD;
        Aspartate amino transferase (AST) (SGOT) and Alanine amino transferase (ALT) (SGPT)≤ 2.0 X&#xD;
        ULN Lipase &lt;1.6 X ULN Alkaline Phosphatase ≤ 2.5 X ULN.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute HIV-1 infection&#xD;
&#xD;
          2. Received blood transfusions or hematopoetic growth factors within 3 months&#xD;
&#xD;
          3. Receipt of compounds with other latency activators within 1 month.&#xD;
&#xD;
          4. Any significant acute medical illness in the past 8 weeks&#xD;
&#xD;
          5. Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen&#xD;
             (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood&#xD;
&#xD;
          6. Patient has the following laboratory values within 3 weeks before starting the&#xD;
             investigational drug Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal&#xD;
             (ULN) Serum total bilirubin ≥1.5 ULN Serum creatinine levels ≥1.5 x ULN, or calculated&#xD;
             creatinine clearance ≤60 ml/min Platelet count ≤100 x109/L Absolute neutrophil count&#xD;
             ≤1.5x109/L Serum potassium, magnesium, phosphorus outside normal limits Total calcium&#xD;
             (corrected for serum albumin) or ionized calcium ≤lower normal limits&#xD;
&#xD;
          7. A personal history of clinically significant cardiac disease, symptomatic or&#xD;
             asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades&#xD;
             de pointes (e.g. heart failure)&#xD;
&#xD;
          8. History of malignancy or transplantation, including skin cancers or Kaposi sarcoma&#xD;
&#xD;
          9. History of diabetes mellitus&#xD;
&#xD;
         10. Known hypersensitivity to Kansui&#xD;
&#xD;
         11. Pregnancy or breast feeding, or expecting to father children within the projected&#xD;
             duration of the study&#xD;
&#xD;
         12. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
             with the requirements of the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hongzhou Lu, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Public Health Clinical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Huanzhang Zhu, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Huanzhang Zhu, M.D.</last_name>
    <phone>31246728</phone>
    <email>hzzhu@fudan.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jingna Xun, MD</last_name>
    <phone>37990333</phone>
    <phone_ext>5321</phone_ext>
    <email>xunjingna@shphc.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai,China, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Huanzhang Zhu, M.D.</last_name>
    </contact>
    <investigator>
      <last_name>Huanzhang Zhu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hongzhou Lu, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://csm.im.ac.cn/templates/team/introduction.aspx?nodeid=10&amp;page=ContentPage&amp;contentid=1950</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Wang P, Lu P, Qu X, Shen Y, Zeng H, Zhu X, Zhu Y, Li X, Wu H, Xu J, Lu H, Ma Z, Zhu H. Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui. Sci Rep. 2017 Aug 25;7(1):9451. doi: 10.1038/s41598-017-07157-0.</citation>
    <PMID>28842560</PMID>
  </reference>
  <reference>
    <citation>Yang H, Li X, Yang X, Lu P, Wang Y, Jiang Z, Pan H, Zhao L, Zhu Y, Khan IU, Shen Y, Lu H, Zhang T, Jiang G, Ma Z, Wu H, Zhu H. Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections. Antiviral Res. 2019 Sep;169:104555. doi: 10.1016/j.antiviral.2019.104555. Epub 2019 Jul 9.</citation>
    <PMID>31295520</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Public Health Clinical Center</investigator_affiliation>
    <investigator_full_name>Hongzhou Lu</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <!-- 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/NCT04503928
org study id: Euphorbia kansui V1
nct id: NCT04503928
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the safety and bioactivity of Euphorbia kansui,
      which has been used in traditional Chinese medicine for the treatment of edema, ascites, and
      asthma. The investigators previously reported that effective fractions from the
      dichloromethane extracts of the roots of Euphorbia kansui can reactivate latent HIV-1
      replication in different latent cells (The 24th China science technology Forum-High level
      Forum on HIV cure, December 16-17, 2012, Beijing). Importantly, in resting CD4+ T cells of
      HIV-1-infected patients on suppressive antiretroviral therapy (ART), it could effectively
      induce ex vivo latent HIV-1 expression. Sera from rats receiving orally administered
      effective fractions were able to reactivate latent HIV-1. The investigators also found a
      substantially potent ingenol derivative EK-16A, EK-1A, EK-5A, EK-15A from Euphorbia kansui
      and proved that it was potent in reversing HIV-1 latency. The investigators' hypothesis is
      that Euphorbia kansui Pill will be safe and well-tolerated and at the doses administered,
      increase HIV transcription in latently-infected cells among HIV-infected patients on
      suppressive antiretroviral therapy.
Every participant will receive oral Euphorbia kansui Pill every day. The dose of Euphorbia
      kansui will be 1g each time for 7 consecutive days. All participants will keep their
      antiretroviral therapy during this study.

      Each step of this study will last for 21 days, involving 7 study visits (Screening,Day 0, 1,
      3, 5, 7, 14, 21) for every participant. At the screening visit, participants will give a
      medical history and will undergo a physical exam; blood samples will be collected.
      Participants will undergo pharmacodynamic sampling which will require that blood be collected
      12 hours after kansui Pill administration on Day 1, 3, 5,7. If participants agree, their
      blood samples may be stored for future research.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: All participants eligible for study received the same open label drug
primary purpose: Treatment
masking: None (Open Label)
masking description: Open label
measure: Change in plasma HIV-1 RNA concentration
time frame: Measured on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21.
measure: Change in cell-associated HIV-1 RNA
time frame: on day 0; 1, 3, 5, 7 (12 hours post administration); 14, 21
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Measured through 21 days after the first administration of kansui Pill
measure: Change in cell-associated total HIV-1 DNA
time frame: Measured on day 0, 14, 21
arm group label: Experimental: Kansui 1g per day x 7 days
arm group type: Experimental
description: Study participants will be given 1 g of Euphorbia kansui Pill for a total of 7 consecutive daily doses.
intervention type: Drug
intervention name: Euphorbia kansui Pill
description: 1 g (10 pills) of Euphorbia kansui Pill taken by mouth, once a day for 7 consecutive days.
arm group label: Experimental: Kansui 1g per day x 7 days
other name: kansui
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hongzhou Lu, M.D.
role: Principal Investigator
affiliation: Shanghai Public Health Clinical Center
last name: Huanzhang Zhu, M.D.
role: Principal Investigator
affiliation: Fudan University
last name: Huanzhang Zhu, M.D.
phone: 31246728
email: hzzhu@fudan.edu.cn
last name: Jingna Xun, MD
phone: 37990333
phone ext: 5321
email: xunjingna@shphc.org.cn
facility: 
contact: 
investigator: 
investigator: 
country: China
url: http://csm.im.ac.cn/templates/team/introduction.aspx?nodeid=10&page=ContentPage&contentid=1950
description: Related Info
citation: Wang P, Lu P, Qu X, Shen Y, Zeng H, Zhu X, Zhu Y, Li X, Wu H, Xu J, Lu H, Ma Z, Zhu H. Reactivation of HIV-1 from Latency by an Ingenol Derivative from Euphorbia Kansui. Sci Rep. 2017 Aug 25;7(1):9451. doi: 10.1038/s41598-017-07157-0.
PMID: 28842560
citation: Yang H, Li X, Yang X, Lu P, Wang Y, Jiang Z, Pan H, Zhao L, Zhu Y, Khan IU, Shen Y, Lu H, Zhang T, Jiang G, Ma Z, Wu H, Zhu H. Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections. Antiviral Res. 2019 Sep;169:104555. doi: 10.1016/j.antiviral.2019.104555. Epub 2019 Jul 9.
PMID: 31295520
responsible party type: Principal Investigator
investigator affiliation: Shanghai Public Health Clinical Center
investigator full name: Hongzhou Lu
investigator title: professor