xml: <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/NCT05984992</url>
    </required_header>
    <id_info>
      <org_study_id>SRN-001-C01</org_study_id>
      <nct_id>NCT05984992</nct_id>
    </id_info>
    <brief_title>The First-in-human Study of SRN-001 in Healthy Participants</brief_title>
    <official_title>A Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of SRN-001 in Healthy Participants</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>siRNAgen Therapeutics Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>siRNAgen Therapeutics Inc.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        SRN-001 is a novel small interfering RNA (siRNA) drug being developed to treat fibrosis using&#xD;
        Self Assembled Micelle inhibitory ribonucleic acid (SAMiRNA™) technology. Amphiregulin (AREG)&#xD;
        is a growth factor involved in fibroblast proliferation and myofibroblast transformation&#xD;
        which is the hallmark of fibrosis in lung and kidney tissues. AREG is a downstream gene&#xD;
        overexpressed by Transforming growth factor-β (TGF-β) during fibrosis, promoting fibroblast&#xD;
        to myofibroblast transition (FMT). SRN-001 is designed to downregulate generating&#xD;
        amphiregulin by RNA interference (RNAi). The goal of this clinical trial is to evaluate&#xD;
        safety, tolerability, and pharmacokinetics in healthy participants. This trial is&#xD;
        first-in-human clinical trial to develop SAMiRNA™ to utilize as therapeutic use.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Participants with part in consent will be enrolled in a phase 1a study of SRN-001. Prior to&#xD;
        initiation of treatment, participants will undergo several screening test for checking their&#xD;
        condition of health. There is no specific test comparing with the general other clinical&#xD;
        trial in healthy volunteers. They will be randomized into two groups, active drug and&#xD;
        inactive placebo(normal saline) as ratio 2:1. Starting dose is planned 15mg. For confirming&#xD;
        maximal tolerable dose, dose will be escalated when no dose-limiting toxicity (DLT)&#xD;
        confirmed. Each cohort will take single dose and for 4 weeks, safety observation will be&#xD;
        taken. If safety abnormality will be retained in 4 weeks, the participant's safety&#xD;
        observation will be prolonged by the end of the adverse event once 2 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 7, 2023</start_date>
    <completion_date type="Anticipated">March 15, 2024</completion_date>
    <primary_completion_date type="Anticipated">January 3, 2024</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>Parallel Assignment</intervention_model>
      <intervention_model_description>Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with treatment-emergent adverse events(TEAEs)</measure>
      <time_frame>Up to 4 weeks</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with serious adverse events(SAEs)</measure>
      <time_frame>Up to 4 weeks</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cmax</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Maximum observed concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clast</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Observed concentration corresponding to Tlast</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tlast</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Time of last measurable observed concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUClast</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Area under the drug concentration-time curve, from time zero to the last measurable concentration</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUCinf</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Area under the drug concentration-time curve, from time zero to infinity</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>T½</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Apparent terminal half-life</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Kel</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Apparent terminal elimination rate constant</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CL</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Total body clearance</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vz</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Volume of distribution</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MRT</measure>
      <time_frame>Up to 168 hours post-dose</time_frame>
      <description>Mean residence time</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Incidence of treatment-emergent Anti-Drug Antibody(ADA)</measure>
      <time_frame>Up to 672 hours post-dose</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Change from baseline in specific biomarkers</measure>
      <time_frame>Up to 24 hours post-dose</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Idiopathic Pulmonary Fibrosis</condition>
    <arm_group>
      <arm_group_label>SRN-001</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SRN-001</intervention_name>
      <description>siRNA therapeutics, Self Assembled Micelle inhibitory RNA platform utilized</description>
      <arm_group_label>SRN-001</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>0.9% Sodium Chloride(Normal saline)</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 18-60&#xD;
  &#xD;
            -  BMI ≥18.0 kg/m2 and ≤32 kg/m2&#xD;
  &#xD;
            -  12-lead triplicate electrocardiogram (ECG) readings within normal limits or with no&#xD;
               clinically significant abnormalities&#xD;
  &#xD;
            -  systolic blood pressure ≥ 90 mmHg and ≤160 mmHg; a diastolic blood pressure ≥ 50 mmHg&#xD;
               and ≤95 mmHg; pulse ≥ 45 bpm and ≤100bpm; tympanic temperature ≥ 35.5°C and ≤37.7°C&#xD;
               and respiratory rate 12rpm to 22rpm&#xD;
  &#xD;
            -  non-smokers&#xD;
  &#xD;
            -  Compliance to contraception restriction&#xD;
  &#xD;
            -  Participants who are able and willing to give written informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Who has clinically significant history&#xD;
  &#xD;
            -  Who is with history of multiple drug allergies or history of allergic reaction to an&#xD;
               oligonucleotide or common medicine or clinically significant hypersensitivity&#xD;
  &#xD;
            -  No tolerance to IV injections or significant potential of intolerance&#xD;
  &#xD;
            -  Clinically significant surgical history within 1 year&#xD;
  &#xD;
            -  History of drug abuse or alcoholism within 2 years&#xD;
  &#xD;
            -  Pregnant or lactating females&#xD;
  &#xD;
            -  Liver function test is 1.5 times greater than upper limit of normal (ULN)&#xD;
  &#xD;
            -  Albumin ≥ 35 g/L and ≤ 50 g/L&#xD;
  &#xD;
            -  Hb &lt; 115 g/L (female), &lt; 125 g/L (male)&#xD;
  &#xD;
            -  estimated glomerular filtration rate (eGFR) &lt; 60 mL/min (CKD-EPI), 90 mL/min (MDRD)&#xD;
  &#xD;
            -  Glucose &lt; 3 mmol/L&#xD;
  &#xD;
            -  Positive screen for alcohol or drugs of abuse&#xD;
  &#xD;
            -  HBsAg, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or HIV infection&#xD;
  &#xD;
            -  QTcF &gt; 450 msec for male, &gt; 470 msec for female&#xD;
  &#xD;
            -  Inappropriate lab result by physician's discretion&#xD;
  &#xD;
            -  Who have donated &gt; 500 mL of blood within 3 months&#xD;
  &#xD;
            -  Who have received an investigational agent within 3 months, or 5 half-lives&#xD;
  &#xD;
            -  Who have used prescription medication within 4 weeks including vaccines&#xD;
  &#xD;
            -  Who have used OTC medication within 7 days&#xD;
  &#xD;
            -  With clinically relevant wounds, following a clinically relevant surgery or have&#xD;
               recently completed any invasive procedures within 1 week&#xD;
  &#xD;
            -  Who have a significant infection or known inflammatory process ongoing&#xD;
  &#xD;
            -  Any conditions that, in physician's opinion,, would make the participant unsuitable&#xD;
               for enrollment or could interfere with the participant's participation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Dongho Kim</last_name>
      <phone>+82-42-930-8654</phone>
      <email>dongho-kim@sirnagen.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>CMAX Clinical Research</name>
        <address>
          <city>Adelaide</city>
          <state>South Australia</state>
          <zip>5000</zip>
          <country>Australia</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Australia</country>
    </location_countries>
    <link>
      <url>https://pubmed.ncbi.nlm.nih.gov/26817844/</url>
      <description>Related Info</description>
    </link>
    <reference>
      <citation>Yoon PO, Park JW, Lee CM, Kim SH, Kim HN, Ko Y, Bae SJ, Yun S, Park JH, Kwon T, Kim WS, Lee J, Lu Q, Kang HR, Cho WK, Elias JA, Yang JS, Park HO, Lee K, Lee CG. Self-assembled Micelle Interfering RNA for Effective and Safe Targeting of Dysregulated Genes in Pulmonary Fibrosis. J Biol Chem. 2016 Mar 18;291(12):6433-46. doi: 10.1074/jbc.M115.693671. Epub 2016 Jan 27.</citation>
      <PMID>26817844</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</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>Pulmonary Fibrosis</mesh_term>
      <mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05984992
  org study id: SRN-001-C01
  nct id: NCT05984992
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  SRN-001 is a novel small interfering RNA (siRNA) drug being developed to treat fibrosis using
        Self Assembled Micelle inhibitory ribonucleic acid (SAMiRNA™) technology. Amphiregulin (AREG)
        is a growth factor involved in fibroblast proliferation and myofibroblast transformation
        which is the hallmark of fibrosis in lung and kidney tissues. AREG is a downstream gene
        overexpressed by Transforming growth factor-β (TGF-β) during fibrosis, promoting fibroblast
        to myofibroblast transition (FMT). SRN-001 is designed to downregulate generating
        amphiregulin by RNA interference (RNAi). The goal of this clinical trial is to evaluate
        safety, tolerability, and pharmacokinetics in healthy participants. This trial is
        first-in-human clinical trial to develop SAMiRNA™ to utilize as therapeutic use.
  Participants with part in consent will be enrolled in a phase 1a study of SRN-001. Prior to
        initiation of treatment, participants will undergo several screening test for checking their
        condition of health. There is no specific test comparing with the general other clinical
        trial in healthy volunteers. They will be randomized into two groups, active drug and
        inactive placebo(normal saline) as ratio 2:1. Starting dose is planned 15mg. For confirming
        maximal tolerable dose, dose will be escalated when no dose-limiting toxicity (DLT)
        confirmed. Each cohort will take single dose and for 4 weeks, safety observation will be
        taken. If safety abnormality will be retained in 4 weeks, the participant's safety
        observation will be prolonged by the end of the adverse event once 2 weeks.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Number of participants with treatment-emergent adverse events(TEAEs)
  time frame: Up to 4 weeks
  measure: Number of participants with serious adverse events(SAEs)
  time frame: Up to 4 weeks
  measure: Cmax
  time frame: Up to 168 hours post-dose
  description: Maximum observed concentration
  measure: Clast
  time frame: Up to 168 hours post-dose
  description: Observed concentration corresponding to Tlast
  measure: Tlast
  time frame: Up to 168 hours post-dose
  description: Time of last measurable observed concentration
  measure: AUClast
  time frame: Up to 168 hours post-dose
  description: Area under the drug concentration-time curve, from time zero to the last measurable concentration
  measure: AUCinf
  time frame: Up to 168 hours post-dose
  description: Area under the drug concentration-time curve, from time zero to infinity
  measure: T½
  time frame: Up to 168 hours post-dose
  description: Apparent terminal half-life
  measure: Kel
  time frame: Up to 168 hours post-dose
  description: Apparent terminal elimination rate constant
  measure: CL
  time frame: Up to 168 hours post-dose
  description: Total body clearance
  measure: Vz
  time frame: Up to 168 hours post-dose
  description: Volume of distribution
  measure: MRT
  time frame: Up to 168 hours post-dose
  description: Mean residence time
  measure: Incidence of treatment-emergent Anti-Drug Antibody(ADA)
  time frame: Up to 672 hours post-dose
  measure: Change from baseline in specific biomarkers
  time frame: Up to 24 hours post-dose
  arm group label: SRN-001
  arm group type: Experimental
  arm group label: Placebo
  arm group type: Placebo Comparator
  intervention type: Drug
  intervention name: SRN-001
  description: siRNA therapeutics, Self Assembled Micelle inhibitory RNA platform utilized
  arm group label: SRN-001
  intervention type: Drug
  intervention name: Placebo
  description: 0.9% Sodium Chloride(Normal saline)
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Dongho Kim
  phone: +82-42-930-8654
  email: dongho-kim@sirnagen.com
  facility: 
  country: Australia
  url: https://pubmed.ncbi.nlm.nih.gov/26817844/
  description: Related Info
  citation: Yoon PO, Park JW, Lee CM, Kim SH, Kim HN, Ko Y, Bae SJ, Yun S, Park JH, Kwon T, Kim WS, Lee J, Lu Q, Kang HR, Cho WK, Elias JA, Yang JS, Park HO, Lee K, Lee CG. Self-assembled Micelle Interfering RNA for Effective and Safe Targeting of Dysregulated Genes in Pulmonary Fibrosis. J Biol Chem. 2016 Mar 18;291(12):6433-46. doi: 10.1074/jbc.M115.693671. Epub 2016 Jan 27.
  PMID: 26817844
  responsible party type: Sponsor
  mesh term: Pulmonary Fibrosis
  mesh term: Idiopathic Pulmonary Fibrosis
  sharing ipd: No