<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/NCT04463017</url>
  </required_header>
  <id_info>
    <org_study_id>RIV-HU6-101</org_study_id>
    <nct_id>NCT04463017</nct_id>
  </id_info>
  <brief_title>Ascending Dose Study of HU6 in Healthy Volunteers</brief_title>
  <official_title>A Double-blind, Placebo-controlled, Phase I Study of the Safety and Pharmacokinetics of Single Ascending Doses of HU6 in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rivus Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rivus Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single ascending dose trial in healthy volunteers. The study will be conducted in&#xD;
      up to 7 cohorts. Upon review of the safety and PK data, it may be decided to expand the&#xD;
      current cohort versus dose escalate to the next cohort. In addition, the sponsor may elect&#xD;
      not to enroll all 7 cohorts based on safety and/or PK and/or PD data.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single ascending dose trial in healthy volunteers. The study will be conducted in&#xD;
      up to 7 cohorts. Upon review of the safety and PK data, it may be decided to expand the&#xD;
      current cohort versus dose escalate to the next cohort. In addition, the sponsor may elect&#xD;
      not to enroll all 7 cohorts based on safety and/or PK and/or PD data.&#xD;
&#xD;
      Up to 74 subjects will be enrolled to allow for replacement subjects, if deemed necessary.&#xD;
      Fewer subjects may be enrolled if not all cohorts are utilized due to identification of the&#xD;
      MTD in an earlier cohort.&#xD;
&#xD;
      Double-blind dosing will occur in cohorts 1 through 7. In these cohorts, 6 subjects will&#xD;
      receive HU6 and 2 will receive matching placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 12, 2020</start_date>
  <completion_date type="Actual">April 1, 2021</completion_date>
  <primary_completion_date type="Actual">March 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>The study will be conducted in one phase: a single dose, dose escalation phase in up to 7 cohorts</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the dose relationship of PK Parameter Cmax</measure>
    <time_frame>3 months</time_frame>
    <description>Following completion of each cohort, bioanalytical analyses for HU6, PK will be performed and plasma PK parameters for Cmax analyzed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess the dose relationship of PK Parameter AUC</measure>
    <time_frame>3 months</time_frame>
    <description>Following completion of each cohort, bioanalytical analyses for HU6, PK will be performed and plasma PK parameters for AUC analyzed</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>NASH - Nonalcoholic Steatohepatitis</condition>
  <arm_group>
    <arm_group_label>Active Treatment: HU6</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Planned doses of HU6; N = 74</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Non-active study drug N = 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HU6</intervention_name>
    <description>HU6 is designed to reduce the steatosis, inflammation, fibrosis and hepatocyte injury in Noncirrhotic Nonalcoholic Steatohepatitis (NASH)</description>
    <arm_group_label>Active Treatment: HU6</arm_group_label>
    <arm_group_label>Placebo Comparator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        TARGET POPULATION:&#xD;
&#xD;
        INCLUSION:&#xD;
&#xD;
        Subjects must meet all the following inclusion criteria to be eligible:&#xD;
&#xD;
          1. Male or female between 18 and 45 years of age, inclusive, at time of informed consent.&#xD;
&#xD;
               1. Female subjects of childbearing potential must be non-lactating, not pregnant as&#xD;
                  confirmed by a negative urine pregnancy test at Screening and admission to&#xD;
                  Clinical Research Unit, and using, and agree to continue using, an effective&#xD;
                  method of contraception for at least 4 weeks prior to first study drug&#xD;
                  administration until 30 days after the last dose of study drug.&#xD;
&#xD;
               2. Female subjects of non-childbearing potential must be surgically sterile (e.g.,&#xD;
                  hysterectomy, bilateral tubal ligation, oophorectomy) or post-menopausal (no&#xD;
                  menses for &gt;1 year with follicle stimulating hormone &gt;40 U/L at Screening)&#xD;
&#xD;
               3. Female subjects of childbearing potential must not donate ova during the study&#xD;
                  and for at least 30 days after the last dose of study drug.&#xD;
&#xD;
               4. Male subjects who have not had a vasectomy and/or Subjects who have had a&#xD;
                  vasectomy but have not had 2 post surgery negative tests for sperm must agree to&#xD;
                  use an acceptable method of contraception from time of first dose of study drug&#xD;
                  until 30 days after the last dose of the study drug, and to not donate sperm&#xD;
                  during the study and for at least 30 days after the last dose of study drug.&#xD;
&#xD;
          2. Healthy per investigator judgment as documented by medical history, physical&#xD;
             examination, vital sign assessments, 12-lead ECG, clinical laboratory assessments, and&#xD;
             general observations.&#xD;
&#xD;
               1. At Screening, abnormalities or deviations outside the normal ranges for any&#xD;
                  clinical assessments that are considered clinically significant by the&#xD;
                  Investigator (laboratory tests, ECG, vital signs) may be repeated once at the&#xD;
                  discretion of the Investigator(s), and results that continue to be outside the&#xD;
                  normal ranges must be judged by the investigator to be not clinically significant&#xD;
                  and acceptable for study participation.&#xD;
&#xD;
               2. On admission to Clinical Research Unit, alanine aminotransferase (ALT), aspartate&#xD;
                  aminotransferase (AST), total bilirubin, and thyroid values must be within the&#xD;
                  upper limits of the normal range. Subjects with isolated elevation of bilirubin&#xD;
                  and presumptive Gilbert's syndrome are permissible. All other laboratory test&#xD;
                  results that are outside the reference range on admission to CRU and judged by&#xD;
                  the investigator to be not clinically significant may optionally be repeated.&#xD;
                  Results that continue to be outside the reference range must be judged by the&#xD;
                  investigator to be not clinically significant and acceptable for study&#xD;
                  participation.&#xD;
&#xD;
               3. Subject must demonstrate clinical euthyroidism as assessed by a thyroid profile&#xD;
                  utilizing TSH and Free T4 testing at screening.&#xD;
&#xD;
          3. Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for&#xD;
             females and 50 kg for males, inclusive. Additional inclusion criteria for the high BMI&#xD;
             single dose cohort:&#xD;
&#xD;
             a. Body mass index &gt; 30.0 kg/m2, waist circumference &gt; 41&quot;&#xD;
&#xD;
          4. Understands the procedures and requirements of the study and provides written informed&#xD;
             consent and authorization for protected health information disclosure.&#xD;
&#xD;
          5. Willing and able to comply with the requirements of the study protocol.&#xD;
&#xD;
        EXCLUSION:&#xD;
&#xD;
        Subjects presenting with any of the following will not qualify for entry into the study:&#xD;
&#xD;
          1. Current or past clinically significant history of cardiovascular, cerebrovascular,&#xD;
             pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic,&#xD;
             urologic, neurologic, dermatologic, psychiatric, or other major disease, as determined&#xD;
             by the investigator. History of cancer (except treated non-melanoma skin cancer) or&#xD;
             history of chemotherapy use within 5 years prior to Screening.&#xD;
&#xD;
          2. Any surgical or medical condition or history that, in the opinion of the investigator,&#xD;
             may potentially alter the absorption, metabolism, or excretion of study treatment,&#xD;
             such as, but not limited to gastric bypass surgery or small bowel resections.&#xD;
&#xD;
          3. Contraindication to study drug or its excipients and/or history of allergic or&#xD;
             anaphylactic reactions.&#xD;
&#xD;
          4. Resting heart rate &lt;45 or &gt;100 bpm; blood pressure &lt; 90 or &gt;140 systolic, or &lt;50 or&#xD;
             &gt;100 diastolic.&#xD;
&#xD;
          5. On screening ECG and by history:&#xD;
&#xD;
               1. A marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration&#xD;
                  of a QTc interval &gt; 450 msec for males and &gt;470 msec for females).&#xD;
&#xD;
               2. A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart&#xD;
                  failure, hypokalemia, family history of Long QT Syndrome).&#xD;
&#xD;
          6. Taking any of the following prohibited medications:&#xD;
&#xD;
             For non-obese cohorts:&#xD;
&#xD;
             a. Any prescription medication (with the exception of all hormonal contraceptives and&#xD;
             hormone replacement therapies (oral, injectable, transdermal or implanted)) or over&#xD;
             the counter multi-vitamin supplement, including products with CBD or any&#xD;
             non-prescription products (including herbal-containing preparations but excluding&#xD;
             acetaminophen) within 14 days prior to admission to CRU.&#xD;
&#xD;
             For obese cohort:&#xD;
&#xD;
             a. Limited background prescription medications are permitted to manage complications&#xD;
             of obesity, but any drug known to inhibit or induce cytochrome P450 (CYP) enzymes&#xD;
             and/or P-glycoprotein including St. John's wort (Hypericum perforatum) within 14 days&#xD;
             or 5 half-lives (whichever is longer) prior to admission to CRU, is prohibited. Also&#xD;
             prohibited is the use of concomitant medications that prolong the QT/QTc interval&#xD;
             identified in the https://crediblemeds.org/ website list category of 'Known Risk'.&#xD;
&#xD;
          7. History of significant drug abuse within one year prior to Screening or use of soft&#xD;
             drugs (such as marijuana) within 3 months prior to the Screening visit or hard drugs&#xD;
             (such as cocaine, phencyclidine [PCP], opioid derivatives including heroin, and&#xD;
             amphetamine derivatives) within 1 year prior to screening.&#xD;
&#xD;
          8. History of regular alcohol consumption exceeding 14 drinks/week [1 drink = 5 ounces&#xD;
             (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor]&#xD;
             within 6 months of Screening.&#xD;
&#xD;
          9. Positive urine drug or urine alcohol test at Screening or on admission to CRU.&#xD;
&#xD;
         10. Current nicotine use or vaping regularly more than 5 cigarettes or the equivalent per&#xD;
             week.&#xD;
&#xD;
         11. Consumed any food or drink/beverage containing grapefruit or grapefruit juice, apple&#xD;
             or orange juice, pomelo juice, star fruit, Seville or Moro (blood) orange products&#xD;
             within 6 days before admission to CRU. Vegetables from the mustard green family (e.g.,&#xD;
             kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, mustard), food&#xD;
             containing poppy seeds (e.g., muffins, bagels, and cakes) must not be consumed within&#xD;
             24 hours before admission to CRU.&#xD;
&#xD;
         12. Positive test results of hepatitis B surface antigen (HBsAg), hepatitis C virus&#xD;
             antibody (HCV Ab), or human immunodeficiency virus (HIV1/2) antibody.&#xD;
&#xD;
         13. Diabetes reflected by a fasting plasma glucose level of ≥126 mg/dL and a reflex HbA1c&#xD;
             of ≥6.5%.&#xD;
&#xD;
         14. Participation in another clinical trial at the time of screening or exposure to any&#xD;
             investigational agent within 30 days or 5 half-lives prior to admission to CRU,&#xD;
             whichever is longer.&#xD;
&#xD;
         15. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding&#xD;
             volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than&#xD;
             499 mL within 56 days prior to the first dosing.&#xD;
&#xD;
         16. Received a tattoo or body piercing (including ear piercings) within 2 months prior to&#xD;
             Day 1, and/or significant open wound that may result in risk of infection.&#xD;
&#xD;
         17. Having a condition that the investigator believes would interfere with his/her ability&#xD;
             to provide written informed consent, comply with study instructions, or which might&#xD;
             confound the interpretation of the study results or put the subject at undue risk.&#xD;
             Subjects with a history of hypo- or hyperthyroidism, peripheral neuropathy, malignant&#xD;
             hyperthermia or chronic recurrent rash that is considered clinically significant by&#xD;
             the investigator are excluded.&#xD;
&#xD;
         18. Must not be claustrophobic or have a history of claustrophobia, or intolerance of&#xD;
             closed or small spaces.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Matson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Prism Research Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Prism Clinical Research</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>May 2, 2021</last_update_submitted>
  <last_update_submitted_qc>May 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NASH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04463017
org study id: RIV-HU6-101
nct id: NCT04463017
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a single ascending dose trial in healthy volunteers. The study will be conducted in
      up to 7 cohorts. Upon review of the safety and PK data, it may be decided to expand the
      current cohort versus dose escalate to the next cohort. In addition, the sponsor may elect
      not to enroll all 7 cohorts based on safety and/or PK and/or PD data.
This is a single ascending dose trial in healthy volunteers. The study will be conducted in
      up to 7 cohorts. Upon review of the safety and PK data, it may be decided to expand the
      current cohort versus dose escalate to the next cohort. In addition, the sponsor may elect
      not to enroll all 7 cohorts based on safety and/or PK and/or PD data.

      Up to 74 subjects will be enrolled to allow for replacement subjects, if deemed necessary.
      Fewer subjects may be enrolled if not all cohorts are utilized due to identification of the
      MTD in an earlier cohort.

      Double-blind dosing will occur in cohorts 1 through 7. In these cohorts, 6 subjects will
      receive HU6 and 2 will receive matching placebo.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The study will be conducted in one phase: a single dose, dose escalation phase in up to 7 cohorts
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Assess the dose relationship of PK Parameter Cmax
time frame: 3 months
description: Following completion of each cohort, bioanalytical analyses for HU6, PK will be performed and plasma PK parameters for Cmax analyzed
measure: Assess the dose relationship of PK Parameter AUC
time frame: 3 months
description: Following completion of each cohort, bioanalytical analyses for HU6, PK will be performed and plasma PK parameters for AUC analyzed
arm group label: Active Treatment: HU6
arm group type: Active Comparator
description: Planned doses of HU6; N = 74
arm group label: Placebo Comparator
arm group type: Placebo Comparator
description: Non-active study drug N = 14
intervention type: Drug
intervention name: HU6
description: HU6 is designed to reduce the steatosis, inflammation, fibrosis and hepatocyte injury in Noncirrhotic Nonalcoholic Steatohepatitis (NASH)
arm group label: Active Treatment: HU6
arm group label: Placebo Comparator
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mark Matson, MD
role: Principal Investigator
affiliation: Prism Research Clinic
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No