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/NCT06024408</url>
    </required_header>
    <id_info>
      <org_study_id>ALN-PNP-NASH-2255</org_study_id>
      <nct_id>NCT06024408</nct_id>
    </id_info>
    <brief_title>A Trial to Learn if Having ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a Genetic Risk Factor</brief_title>
    <official_title>A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALN-PNP siRNA in Participants With Nonalcoholic Fatty Liver Disease (NAFLD) and a PNPLA3 Genetic Risk Factor</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Regeneron Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Regeneron Pharmaceuticals</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>
        The study is researching an experimental drug called ALN-PNP. The study is focused on&#xD;
        participants who are known to have non-alcoholic fatty liver disease (NAFLD), and a specific&#xD;
        variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene.&#xD;
  &#xD;
        The aim of the study is to see how safe, tolerable, and effective the study drug is.&#xD;
  &#xD;
        The study is looking at several other research questions, including:&#xD;
  &#xD;
          -  What side effects may happen from taking the study drug&#xD;
  &#xD;
          -  How ALN-PNP works to change liver fat content in NAFLD&#xD;
  &#xD;
          -  How much study drug and study drug metabolites (byproduct of the body breaking down the&#xD;
             study drug) are in your blood at different times&#xD;
  &#xD;
          -  Whether the body makes antibodies against the study drug (which could make the drug less&#xD;
             effective or could lead to side effects)&#xD;
  &#xD;
          -  Better understanding of the study drug and NAFLD&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 24, 2023</start_date>
    <completion_date type="Anticipated">January 8, 2026</completion_date>
    <primary_completion_date type="Anticipated">January 8, 2026</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of treatment-emergent adverse events (TEAEs)</measure>
      <time_frame>Through End of Study (EOS), Up to 253 days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Severity of TEAEs</measure>
      <time_frame>Through EOS, Up to 253 days</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in liver fat fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in participants with NAFLD</measure>
      <time_frame>Baseline up to 169 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD</measure>
      <time_frame>Baseline up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in High-density lipoprotein cholesterol (HDL-C) in participants with NAFLD</measure>
      <time_frame>Baseline up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Triglycerides (TG) in participants with NAFLD</measure>
      <time_frame>Baseline up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Lipoprotein a (Lp(a)) in participants with NAFLD</measure>
      <time_frame>Baseline up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Apolipoprotein A1 (ApoA1) in participants with NAFLD</measure>
      <time_frame>Baseline up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Apolipoprotein B (ApoB) in participants with NAFLD</measure>
      <time_frame>Baseline up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of ALN-PNP and potential major metabolite(s) in plasma over time</measure>
      <time_frame>Up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of anti-drug antibodies (ADAs) to ALN-PNP</measure>
      <time_frame>Up to 253 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Titer of anti-drug antibodies (ADAs) to ALN-PNP</measure>
      <time_frame>Up to 253 days</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">96</enrollment>
    <condition>Nonalcoholic Steatohepatitis</condition>
    <condition>Genetic Risk Factor</condition>
    <arm_group>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants who are homozygous for the PNPLA3 risk allele (G/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants who are heterozygous for the PNPLA3 risk allele (C/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ALN-PNP Dose Level 1</intervention_name>
      <description>Administered by subcutaneous (SC) injection, every 4 weeks (Q4W) x 4 doses</description>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_label>Cohort 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ALN-PNP Dose Level 2</intervention_name>
      <description>Administered SC, Q4w x 4 doses</description>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_label>Cohort 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>ALN-PNP Dose Level 3</intervention_name>
      <description>Administered SC, Q4W x 4 doses</description>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_label>Cohort 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Matching Placebo</intervention_name>
      <description>Administered SC, Q4W x 4 doses</description>
      <arm_group_label>Cohort 1</arm_group_label>
      <arm_group_label>Cohort 2</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            1. Participants from 18 (or country's legal age of adulthood) to 65 years of age,&#xD;
               inclusive, at screening visit 1&#xD;
  &#xD;
            2. Body mass index (BMI) from 23.0 kg/m^2 to 40.0 kg/m^2, inclusive, for East Asians&#xD;
               (including but not limited to South Koreans, Chinese, Taiwanese, and Japanese) and BMI&#xD;
               from 27.0 kg/m^2 to 40.0 kg/m^2, inclusive, for any other ethnicity at screening visit&#xD;
               1&#xD;
  &#xD;
            3. Meets genotype criteria for the rs738409:G PNPLA3 risk allele: homozygotes or&#xD;
               heterozygotes; p.I148M variant (PNPLA3 rs738409:G [p.I148M]) at screening visit 1&#xD;
  &#xD;
            4. Liver fat content ≥8.5% as measured by MRI-PDFF at screening visit 3&#xD;
  &#xD;
            5. Generally stable diet (based on participant's recall) for at least 3 months prior to&#xD;
               the screening visit&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            1. Evidence of other forms of known chronic liver disease, as defined in the protocol&#xD;
  &#xD;
            2. Has a contraindication to MRI examinations, such as persons with cardiac pacemaker and&#xD;
               implants made out of metal (for example, cochlear implant, nerve stimulators, magnetic&#xD;
               vascular clips, and metallic heart valve), severe claustrophobia, or other&#xD;
               contraindications for MRI&#xD;
  &#xD;
            3. Is taking a medication to treat a co-morbid condition that is not permitted during the&#xD;
               study&#xD;
  &#xD;
            4. Has any laboratory parameter assessments a screening, as defined in the protocol&#xD;
  &#xD;
            5. History of Type 1 diabetes&#xD;
  &#xD;
            6. Bariatric surgery within approximately 5 years prior or planned during the study&#xD;
               period&#xD;
  &#xD;
            7. Has lost or gained more than 4.0% body weight over the 3 months prior to or during the&#xD;
               screening period&#xD;
  &#xD;
            8. Has known human immunodeficiency virus (HIV) infection, evidence of current or chronic&#xD;
               hepatitis B virus (HBV) infection, or current or chronic hepatitis C virus (HCV)&#xD;
               infection, as defined in the protocol&#xD;
  &#xD;
            9. Was hospitalized (ie, &gt;24 hours) for any reason within 30 days of the screening visit&#xD;
  &#xD;
          Note: Other protocol defined Inclusion/Exclusion Criteria apply&#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>Clinical Trial Management</last_name>
      <role>Study Director</role>
      <affiliation>Regeneron Pharmaceuticals</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Clinical Trials Administrator</last_name>
      <phone>844-734-6643</phone>
      <email>clinicaltrials@regeneron.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 16, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>NASH</keyword>
    <keyword>Nonalcoholic Fatty Liver Disease</keyword>
    <keyword>NAFLD</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>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.</ipd_time_frame>
      <ipd_access_criteria>Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf</ipd_access_criteria>
      <ipd_url>https://vivli.org/</ipd_url>
    </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/NCT06024408
  org study id: ALN-PNP-NASH-2255
  nct id: NCT06024408
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The study is researching an experimental drug called ALN-PNP. The study is focused on
        participants who are known to have non-alcoholic fatty liver disease (NAFLD), and a specific
        variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene.
  
        The aim of the study is to see how safe, tolerable, and effective the study drug is.
  
        The study is looking at several other research questions, including:
  
          -  What side effects may happen from taking the study drug
  
          -  How ALN-PNP works to change liver fat content in NAFLD
  
          -  How much study drug and study drug metabolites (byproduct of the body breaking down the
             study drug) are in your blood at different times
  
          -  Whether the body makes antibodies against the study drug (which could make the drug less
             effective or could lead to side effects)
  
          -  Better understanding of the study drug and NAFLD
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Incidence of treatment-emergent adverse events (TEAEs)
  time frame: Through End of Study (EOS), Up to 253 days
  measure: Severity of TEAEs
  time frame: Through EOS, Up to 253 days
  measure: Change in liver fat fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in participants with NAFLD
  time frame: Baseline up to 169 days
  measure: Change in Low-density lipoprotein cholesterol (LDL-C) in participants with NAFLD
  time frame: Baseline up to 253 days
  measure: Change in High-density lipoprotein cholesterol (HDL-C) in participants with NAFLD
  time frame: Baseline up to 253 days
  measure: Change in Triglycerides (TG) in participants with NAFLD
  time frame: Baseline up to 253 days
  measure: Change in Lipoprotein a (Lp(a)) in participants with NAFLD
  time frame: Baseline up to 253 days
  measure: Change in Apolipoprotein A1 (ApoA1) in participants with NAFLD
  time frame: Baseline up to 253 days
  measure: Change in Apolipoprotein B (ApoB) in participants with NAFLD
  time frame: Baseline up to 253 days
  measure: Concentration of ALN-PNP and potential major metabolite(s) in plasma over time
  time frame: Up to 253 days
  measure: Incidence of anti-drug antibodies (ADAs) to ALN-PNP
  time frame: Up to 253 days
  measure: Titer of anti-drug antibodies (ADAs) to ALN-PNP
  time frame: Up to 253 days
  arm group label: Cohort 1
  arm group type: Experimental
  description: Participants who are homozygous for the PNPLA3 risk allele (G/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo
  arm group label: Cohort 2
  arm group type: Experimental
  description: Participants who are heterozygous for the PNPLA3 risk allele (C/G) Randomized 3:1 within three dose levels to ALN-PNP or placebo
  intervention type: Drug
  intervention name: ALN-PNP Dose Level 1
  description: Administered by subcutaneous (SC) injection, every 4 weeks (Q4W) x 4 doses
  arm group label: Cohort 1
  arm group label: Cohort 2
  intervention type: Drug
  intervention name: ALN-PNP Dose Level 2
  description: Administered SC, Q4w x 4 doses
  arm group label: Cohort 1
  arm group label: Cohort 2
  intervention type: Drug
  intervention name: ALN-PNP Dose Level 3
  description: Administered SC, Q4W x 4 doses
  arm group label: Cohort 1
  arm group label: Cohort 2
  intervention type: Drug
  intervention name: Matching Placebo
  description: Administered SC, Q4W x 4 doses
  arm group label: Cohort 1
  arm group label: Cohort 2
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Clinical Trial Management
  role: Study Director
  affiliation: Regeneron Pharmaceuticals
  last name: Clinical Trials Administrator
  phone: 844-734-6643
  email: clinicaltrials@regeneron.com
  responsible party type: Sponsor
  mesh term: Liver Diseases
  mesh term: Fatty Liver
  mesh term: Non-alcoholic Fatty Liver Disease
  sharing ipd: Yes
  ipd description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
  ipd access criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
  ipd url: https://vivli.org/