<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/NCT03261739</url>
  </required_header>
  <id_info>
    <org_study_id>BRB-018-001-US</org_study_id>
    <nct_id>NCT03261739</nct_id>
  </id_info>
  <brief_title>Safety Tolerability, and PK of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)</brief_title>
  <official_title>An Adaptive Design Study for the Assessment of the Safety, Tolerability, and Pharmacokinetics of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bird Rock Bio, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ProSciento, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Perspectum</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bird Rock Bio, Inc.</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>
      BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate&#xD;
      the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BRB-018-001 will be conducted as a multicenter, adaptive design, randomized, parallel group&#xD;
      study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects&#xD;
      with NAFLD. Subjects in each cohort shall be randomized to either RYI-018 or placebo as&#xD;
      weekly injection for four weeks. The active doses of RYI-018 will be as follows: Cohort 1:&#xD;
      0.6 mg/kg, Cohort 2: 1.2 mg/kg, and Cohort 3: 2.5 mg/kg. Primary endpoints include safety and&#xD;
      tolerability. Secondary endpoints include pharmacokinetics and immunogenicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Actual">August 24, 2018</completion_date>
  <primary_completion_date type="Actual">August 24, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Randomized, placebo controlled, with 3 sequential cohorts</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blind, placebo controlled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical evaluation of adverse events</measure>
    <time_frame>Continuous through 67 days</time_frame>
    <description>Subjects will be assessed for adverse events attributable to RYI-018</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to peak serum concentration</measure>
    <time_frame>Week 1, Week 4</time_frame>
    <description>Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as occurring at tmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak serum concentration</measure>
    <time_frame>Week 1, Week 4</time_frame>
    <description>Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration versus time curve (AUC)</measure>
    <time_frame>Week 1, Week 4</time_frame>
    <description>Serum concentrations after single and multiple doses of RYI-018 will be measured and the AUC will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution</measure>
    <time_frame>Week 1, Week 4</time_frame>
    <description>Serum concentrations after single and multiple doses of RYI-018 will be measured and the apparent volume of distribution, Vz, will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.</measure>
    <time_frame>Days 8, 15, 22, 29, 36, 67</time_frame>
    <description>Serum samples at multiple timepoints will be collected for quantitation of anti-RYI-018 antibodies.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>NAFLD</condition>
  <arm_group>
    <arm_group_label>RYI- 018</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The doses of RYI-018 to be evaluated in sequential cohorts will be 0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>vehicle control</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RYI-018</intervention_name>
    <description>Anti-CB1 monoclonal antibody</description>
    <arm_group_label>RYI- 018</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Adult male or females, 18 to 65 years of age (inclusive) at the time of screening.&#xD;
&#xD;
          2. BMI ≥25.0 and ≤40.0 (kg/m2) (inclusive).&#xD;
&#xD;
          3. Liver ultrasound (or transient elastography if approved by medical monitor) which&#xD;
             qualitatively shows fatty liver or documented history of NAFLD.&#xD;
&#xD;
          4. Liver fat percentage by MRI of approximately 10% or greater (MRI to be performed only&#xD;
             in subjects with documented NAFLD or fatty liver by ultrasound or transient&#xD;
             elastography if approved by medical monitor).&#xD;
&#xD;
          5. Type 2 diabetes or prediabetes.&#xD;
&#xD;
          6. Negative urine drug screen/alcohol breath test at screening.&#xD;
&#xD;
          7. Non-smokers as defined by not smoked any tobacco or nicotine-containing products&#xD;
             within 3 months prior to screening. No current use of any nicotine containing product.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Positive serologic testing for HIV, HBsAg, or HCV.&#xD;
&#xD;
          2. Have any known malignancy or history of malignancy, except for basal cell or squamous&#xD;
             cell skin cancer that has been treated with no evidence of recurrence for at least 3&#xD;
             months prior to Screening.&#xD;
&#xD;
          3. Have any underlying physical or psychological medical condition that, in the opinion&#xD;
             of the Investigator or sponsor, would make it unlikely that the subject will complete&#xD;
             the study or is not in the subject's best interest&#xD;
&#xD;
          4. Liver function tests AST or ALT &gt;5 x ULN at screening. One repeat test may be allowed&#xD;
             within 7 days at the discretion of the Investigator.&#xD;
&#xD;
          5. Total bilirubin &gt; ULN at screening except in patients with a known history of&#xD;
             Gilbert's syndrome.&#xD;
&#xD;
          6. History or presence of alcoholism or drug abuse within the 2 years prior to the first&#xD;
             study drug administration.&#xD;
&#xD;
          7. Administration of IP in another trial within 30 Days or 5 times the investigational&#xD;
             drug half-life, whichever is longer, prior to the first study drug administration.&#xD;
&#xD;
          8. History of cerebrovascular event acute coronary syndrome within 6 months of screening.&#xD;
&#xD;
          9. Any history of seizures, major depression, suicidality, or unexplained syncope.&#xD;
&#xD;
         10. Subjects with other active (acute or chronic) liver disease other than NAFLD/NASH&#xD;
             (e.g., autoimmune liver disease, viral hepatitis, genetic hemochromatosis, Wilson&#xD;
             disease, alpha-1-antitrypsin deficiency, alcohol liver disease, drug induced liver&#xD;
             disease).&#xD;
&#xD;
         11. Use of prescription or non-prescription weight loss medications, thiazolidinediones,&#xD;
             investigational or approved medications for NASH, or antidepressant medications within&#xD;
             90 days of screening.&#xD;
&#xD;
         12. Use of insulin injections within 30 days of screening.&#xD;
&#xD;
         13. History of bariatric surgery or plans for bariatric surgery or an attempt to lose&#xD;
             weight during study.&#xD;
&#xD;
         14. Daily alcohol intake &gt;20 g/day for women and &gt;30 g/day for men (on average per day),&#xD;
             as per medical history.&#xD;
&#xD;
         15. Subjects with renal dysfunction estimated glomerular filtration rate &lt;60 mL/min/1.73&#xD;
             m2.&#xD;
&#xD;
         16. HbA1c &gt;9.5% at screening.&#xD;
&#xD;
         17. Pregnant or breastfeeding women.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>BRB Site</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRB Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33147</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRB Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRB Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRB Site</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRB Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4G 3E8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>March 13, 2019</last_update_submitted>
  <last_update_submitted_qc>March 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT03261739
org study id: BRB-018-001-US
nct id: NCT03261739
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate
      the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD.
BRB-018-001 will be conducted as a multicenter, adaptive design, randomized, parallel group
      study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects
      with NAFLD. Subjects in each cohort shall be randomized to either RYI-018 or placebo as
      weekly injection for four weeks. The active doses of RYI-018 will be as follows: Cohort 1:
      0.6 mg/kg, Cohort 2: 1.2 mg/kg, and Cohort 3: 2.5 mg/kg. Primary endpoints include safety and
      tolerability. Secondary endpoints include pharmacokinetics and immunogenicity.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Randomized, placebo controlled, with 3 sequential cohorts
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double blind, placebo controlled
measure: Clinical evaluation of adverse events
time frame: Continuous through 67 days
description: Subjects will be assessed for adverse events attributable to RYI-018
measure: Time to peak serum concentration
time frame: Week 1, Week 4
description: Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as occurring at tmax.
measure: Peak serum concentration
time frame: Week 1, Week 4
description: Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as Cmax.
measure: Area under the serum concentration versus time curve (AUC)
time frame: Week 1, Week 4
description: Serum concentrations after single and multiple doses of RYI-018 will be measured and the AUC will be calculated.
measure: Apparent volume of distribution
time frame: Week 1, Week 4
description: Serum concentrations after single and multiple doses of RYI-018 will be measured and the apparent volume of distribution, Vz, will be calculated.
measure: Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.
time frame: Days 8, 15, 22, 29, 36, 67
description: Serum samples at multiple timepoints will be collected for quantitation of anti-RYI-018 antibodies.
arm group label: RYI- 018
arm group type: Experimental
description: The doses of RYI-018 to be evaluated in sequential cohorts will be 0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg.
arm group label: Placebo
arm group type: Placebo Comparator
description: vehicle control
intervention type: Biological
intervention name: RYI-018
description: Anti-CB1 monoclonal antibody
arm group label: RYI- 018
intervention type: Biological
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease