<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/NCT02227459</url>
  </required_header>
  <id_info>
    <org_study_id>ND-L02-s0201-002</org_study_id>
    <nct_id>NCT02227459</nct_id>
  </id_info>
  <brief_title>Phase 1b/2, Open Label, Repeat Dose, Dose Escalation Study of ND-L02-s0201 Injection in Subjects With Moderate to Extensive Fibrosis (METAVIR F3-4)</brief_title>
  <official_title>A Phase 1b/2, Open Label, Randomized, Repeat Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Biological Activity, and Pharmacokinetics of ND-L02-s0201 Injection, A Vitamin A-coupled Lipid Nanoparticle Containing siRNA Against HSP47, in Subjects With Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nitto Denko Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bristol-Myers Squibb</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and tolerability of multiple doses of&#xD;
      ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with serious and non-serious adverse events</measure>
    <time_frame>After treatment for 5 consecutive weeks and follow-up through week 24</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Moderate to Extensive Hepatic Fibrosis (METAVIR F3-4)</condition>
  <arm_group>
    <arm_group_label>Experimental: Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once a week dosing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twice a week dosing</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ND-L02-s0201 Injection</intervention_name>
    <arm_group_label>Experimental: Arm A</arm_group_label>
    <arm_group_label>Experimental: Arm B</arm_group_label>
    <other_name>BMS-986263</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female between 18 and 75 years&#xD;
&#xD;
          2. Diagnosis of METAVIR F3-4 hepatic fibrosis determined by liver biopsy done within 12&#xD;
             months before screening (Cohort 1) or at the pre-dose biopsy within 6 weeks before&#xD;
             treatment (Cohorts 2 and 3)&#xD;
&#xD;
          3. Adequate and stable synthetic hepatic function (albumin ≥ 3 g/dL, international&#xD;
             normalized ratio [INR] ≤ 1.4 x upper limit of normal [ULN] and stable by prior medical&#xD;
             history).&#xD;
&#xD;
          4. Adequate and stable hepatic function as measured by alkaline phosphatase (ALP),&#xD;
             alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamate transferase&#xD;
             (GGTP), and total bilirubin (ALT/AST ≤ 5 x ULN, ALP ≤ 4 x ULN, GGTP ≤ 4 x ULN,&#xD;
             bilirubin ≤ 2x ULN and stable by prior medical history).&#xD;
&#xD;
          5. Platelet count ≥ 75,000/mm3, hemoglobin ≥ 10 g/dL, and white blood cell count (WBC) &gt;&#xD;
             3000/µL.&#xD;
&#xD;
          6. No signs of decompensated liver disease (ascites, hepatic encephalopathy, or variceal&#xD;
             bleeding).&#xD;
&#xD;
          7. No clinically significant abnormalities on 12-lead electrocardiogram (ECG).&#xD;
&#xD;
          8. No other intercurrent medical conditions or infections considered clinically&#xD;
             significant by the Investigator.&#xD;
&#xD;
          9. Clinical laboratory assessments are within the laboratory limits of normal values or&#xD;
             not considered clinically significant by the Investigator.&#xD;
&#xD;
         10. Vitamin A levels at screening must be less than or equal to the upper limit of normal&#xD;
             (ULN 95 µg/dL or 3.32 µmol/L).&#xD;
&#xD;
         11. Any male subject, if sexually active, agrees to use barrier contraceptive techniques&#xD;
             as defined in the protocol. If female, the subject must be of non-childbearing&#xD;
             potential as defined in the protocol.&#xD;
&#xD;
         12. Subjects who are active substances abusers may be enrolled at the discretion of the&#xD;
             Principal Investigator.&#xD;
&#xD;
         13. Willing and able to provide written informed consent and comply with the study&#xD;
             procedures and visit schedule, including follow up visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any disease or condition which, in the opinion of the Investigator, might compromise&#xD;
             the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic,&#xD;
             skeletal, or central nervous system; or other conditions that may interfere with the&#xD;
             absorption, distribution, metabolism, or excretion of ND L02 s0201, or would place the&#xD;
             subject at increased risk.&#xD;
&#xD;
          2. On ongoing therapy for HCV/HBV, or received therapy for HCV/HBV within 12 weeks prior&#xD;
             to administration of study drug.&#xD;
&#xD;
          3. On interferon therapy for any disease or received interferon therapy for any disease&#xD;
             within 12 weeks prior to administration of study drug.&#xD;
&#xD;
          4. History of bone disease, including osteoporosis and osteomalacia, Paget's disease of&#xD;
             bone, or a history of unexplained fractures or fractures after minimal trauma.&#xD;
&#xD;
          5. Alpha-fetoprotein (AFP) ≥ 50 ng/mL or signs of abnormality or hepatocellular carcinoma&#xD;
             on ultrasound survey of the liver.&#xD;
&#xD;
          6. Carcinoembryonic antigen (CEA) levels above the ULN.&#xD;
&#xD;
          7. Laboratory test results include abnormal values considered to be clinically&#xD;
             significant by the Investigator.&#xD;
&#xD;
          8. Participated in a concurrent interventional study with the last intervention occurring&#xD;
             within 12 weeks prior to administration of study drug.&#xD;
&#xD;
          9. Taken vitamin A or vitamin D supplements or multi-vitamins that contain vitamin A or&#xD;
             vitamin D between the screening visit and administration of study drug.&#xD;
&#xD;
         10. History, within the last 2 years, of alcohol abuse, significant mental illness, or&#xD;
             physical dependence on any opioid.&#xD;
&#xD;
         11. Veins unsuitable for repeated venipuncture or IV infusion (eg, veins that are&#xD;
             difficult to locate, access or puncture; veins with a tendency to rupture during or&#xD;
             after puncture).&#xD;
&#xD;
         12. Received recent treatment with alternative therapies, which, in the opinion of the&#xD;
             Investigator, could potentially confound clinical or laboratory assessments.&#xD;
&#xD;
         13. Lost more than 500 mL of blood within 56 days prior to administration of study drug.&#xD;
&#xD;
         14. Body mass index (BMI) &gt; 38 kg/m2.&#xD;
&#xD;
         15. History of human immunodeficiency virus (HIV) or acquired immunodeficiency&#xD;
             syndrome-related illness (AIDS).&#xD;
&#xD;
         16. History of malignancy within the last 5 years with the exception of basal cell&#xD;
             carcinoma.&#xD;
&#xD;
         17. Woman of childbearing potential.&#xD;
&#xD;
         18. History of hypersensitivity to H2-receptor antagonists.&#xD;
&#xD;
         19. Any other reason that, in the opinion of the Investigator or the Sponsor's Medical&#xD;
             Monitor, makes the subject unsuitable for enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eric Lawitz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Texas Liver Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rozalina Balabanska, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tokuda Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Texas Liver Institute</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokuda Hospital</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>May 9, 2017</last_update_submitted>
  <last_update_submitted_qc>May 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrosis</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/NCT02227459
org study id: ND-L02-s0201-002
nct id: NCT02227459
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the safety and tolerability of multiple doses of
      ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with serious and non-serious adverse events
time frame: After treatment for 5 consecutive weeks and follow-up through week 24
arm group label: Experimental: Arm A
arm group type: Experimental
description: Once a week dosing
arm group label: Experimental: Arm B
arm group type: Experimental
description: Twice a week dosing
intervention type: Drug
intervention name: ND-L02-s0201 Injection
arm group label: Experimental: Arm A
arm group label: Experimental: Arm B
other name: BMS-986263
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Eric Lawitz, MD
role: Principal Investigator
affiliation: Texas Liver Institute
last name: Rozalina Balabanska, MD
role: Principal Investigator
affiliation: Tokuda Hospital
facility: 
facility: 
country: Bulgaria
country: United States
responsible party type: Sponsor
mesh term: Fibrosis