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/NCT05972629</url>
    </required_header>
    <id_info>
      <org_study_id>DFI17545</org_study_id>
      <secondary_id>U1111-1271-1293</secondary_id>
      <secondary_id>2022-501200-98</secondary_id>
      <nct_id>NCT05972629</nct_id>
    </id_info>
    <brief_title>A Phase 1/Phase 2 Open-label Study to Evaluate the Safety, Tolerability, and Efficacy of a Single Intravenous Administration of SAR444836 in Adult Participants With Phenylketonuria</brief_title>
    <official_title>A Phase 1/Phase 2, Open-label, Dose-escalation, and Dose Expansion Study to Evaluate the Safety, Tolerability, and Efficacy of SAR444836, an Adeno-associated Viral Vector-mediated Gene Transfer of Human Phenylalanine Hydroxylase, in Adult Participants With Phenylketonuria</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sanofi</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sanofi</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>
        This is a single group Phase 1/Phase 2, 1-arm, open-label study with SAR444836, an&#xD;
        adeno-associated virus (AAV) vector-mediated gene transfer of human phenylalanine hydroxylase&#xD;
        (PAH), for the treatment of adult participants with phenylketonuria (PKU) on a chronic,&#xD;
        stable diet. The purpose of the study is to evaluate the safety and efficacy of SAR444836 in&#xD;
        reducing phenylalanine (Phe) levels and in the elimination of a Phe restricted diet.&#xD;
  &#xD;
        Participants will receive a one-time intravenous (IV) administration of SAR444836.&#xD;
  &#xD;
        The study is constituted of 2 separate parts: a dose escalation part, and a dose expansion&#xD;
        part where subsequent participants will be administered a safe and effective dose level&#xD;
        identified during the dose escalation part. In both study parts, clinical and laboratory&#xD;
        assessments will be collected to: a) assess the incidence of adverse events, and b) evaluate&#xD;
        the effect of SAR444836 on reductions in blood Phe levels and maintenance of these Phe levels&#xD;
        after elimination of a Phe restricted diet.&#xD;
  &#xD;
        The study duration will be approximately 102 weeks (approximately 2 years) for each&#xD;
        participant and includes a 6-week screening phase and 96-week follow-up period after&#xD;
        SAR444836 administration.&#xD;
  &#xD;
        There will be a total of 41 study visits. Many study visits may occur as remote visits and be&#xD;
        performed by a qualified in-home service provider.&#xD;
  &#xD;
        Actual study duration for an individual participant may be longer than 102 weeks due to the&#xD;
        administration of SAR444836 to participants in Stage 1A in a serial fashion, or other factors&#xD;
        such as delays in scheduling study visits.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 7, 2023</start_date>
    <completion_date type="Anticipated">July 2027</completion_date>
    <primary_completion_date type="Anticipated">July 2027</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of treatment-emergent adverse events (TEAEs)</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with sustained plasma level of Phe&lt;360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in plasma level of Phe at Week 24 and Week 96 or End of Study following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in dietary protein intake at Week 24 and Week 96 or End of Study following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with sustained plasma level of Phe &lt;600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with sustained plasma level of Phe &lt;120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in plasma Phe: Tyr ratio at Week 24 and Week 96 or End of Study following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants with abnormal laboratory chemistry values</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the duration of viral vector shedding of SAR444836 in sampling of urine, saliva, and semen at 4-week intervals following SAR444836 administration</measure>
      <time_frame>From Baseline to Week 96</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">32</enrollment>
    <condition>Phenylketonuria</condition>
    <arm_group>
      <arm_group_label>SAR444836</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive a single dose of SAR444836 on Day 1</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SAR444836</intervention_name>
      <description>Infusion pump, intravenous infusion (IV)</description>
      <arm_group_label>SAR444836</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Adult males, and females of non-child bearing potential, 18-65 years of age at the&#xD;
               time of informed consent.&#xD;
  &#xD;
            -  Participants who have the diagnosis of PKU due to PAH deficiency&#xD;
  &#xD;
            -  One historical plasma Phe value ≥ 600 μmol/L in the preceding 24 months while on Phe&#xD;
               restricted diet therapy. Two plasma Phe values ≥ 600 μmol/L drawn at least 72 hours&#xD;
               apart during the screening period while on Phe restricted diet therapy in the absence&#xD;
               of an acute illness.&#xD;
  &#xD;
            -  Participant has the ability and willingness to maintain their present diet for the&#xD;
               duration of the trial, unless otherwise directed as per protocol&#xD;
  &#xD;
            -  Body mass index (BMI) ≤ 35 kg/m2&#xD;
  &#xD;
            -  Willingness to use effective methods of contraception.&#xD;
  &#xD;
            -  Capable of giving signed informed consent which includes compliance with the&#xD;
               requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
               protocol.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence of neutralizing antibodies against the AAV SNY001 capsid&#xD;
  &#xD;
            -  Abnormal liver function laboratory testing evidenced by alanine aminotransferase&#xD;
               (ALT)&gt;1.5X upper limit normal (ULN), aspartate transaminase (AST)&gt;1.5X ULN, alkaline&#xD;
               phosphatase &gt;1.5X ULN, Total and direct bilirubin &gt;1.5X ULN (bilirubin levels above&#xD;
               the laboratory's normal range are acceptable in individuals with a documented history&#xD;
               or laboratory evidence of Gilbert's Disease)&#xD;
  &#xD;
            -  Any significant underlying liver disease or any of the following documented diagnoses,&#xD;
               indicative of significant underlying liver disease:&#xD;
  &#xD;
                 -  Portal hypertension; or&#xD;
  &#xD;
                 -  Splenomegaly; or&#xD;
  &#xD;
                 -  Hepatic encephalopathy&#xD;
  &#xD;
            -  Serum albumin measurement below the lower limit of normal of the laboratory OR&#xD;
               AST-to-Platelet Ratio Index &gt; 1.0&#xD;
  &#xD;
            -  Serum creatinine &gt;1.5X ULN&#xD;
  &#xD;
            -  Hemoglobin A1c &gt;6.5% or fasting glucose &gt;126 mg/dL&#xD;
  &#xD;
            -  Screening laboratory testing demonstrating any of the following:&#xD;
  &#xD;
                 -  HIV; or&#xD;
  &#xD;
                 -  active or prior hepatitis B virus (HBV) infection defined as positive test for&#xD;
                    hepatitis B surface antigen (HBsAg) or positive test for hepatitis B core&#xD;
                    antibody (total HBcAb) or detectable HBV DNA; or&#xD;
  &#xD;
                 -  active hepatitis C virus (HCV) infection defined as positive test for hepatitis C&#xD;
                    antibody followed by detectable HCV RNA or if a participant is presently&#xD;
                    receiving (or has received within 6 months prior to screening) anti-viral therapy&#xD;
                    for hepatitis C&#xD;
  &#xD;
            -  Clinically significant, active bacterial, viral, fungal, or parasitic infection (based&#xD;
               on Investigator's judgement)&#xD;
  &#xD;
          The above information is not intended to contain all considerations relevant to a potential&#xD;
          participation in a clinical trial.&#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 Sciences &amp;amp; Operations</last_name>
      <role>Study Director</role>
      <affiliation>Sanofi</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Trial Transparency email recommended (Toll free for US &amp;amp; Canada)</last_name>
      <phone>800-633-1610</phone>
      <phone_ext>option 6</phone_ext>
      <email>Contact-US@sanofi.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Investigational Site Number: 7920001</name>
        <address>
          <city>Ankara</city>
          <zip>06351</zip>
          <country>Turkey</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>Turkey</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 23, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 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>Phenylketonurias</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
    </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/NCT05972629
  org study id: DFI17545
  secondary id: U1111-1271-1293
  secondary id: 2022-501200-98
  nct id: NCT05972629
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a single group Phase 1/Phase 2, 1-arm, open-label study with SAR444836, an
        adeno-associated virus (AAV) vector-mediated gene transfer of human phenylalanine hydroxylase
        (PAH), for the treatment of adult participants with phenylketonuria (PKU) on a chronic,
        stable diet. The purpose of the study is to evaluate the safety and efficacy of SAR444836 in
        reducing phenylalanine (Phe) levels and in the elimination of a Phe restricted diet.
  
        Participants will receive a one-time intravenous (IV) administration of SAR444836.
  
        The study is constituted of 2 separate parts: a dose escalation part, and a dose expansion
        part where subsequent participants will be administered a safe and effective dose level
        identified during the dose escalation part. In both study parts, clinical and laboratory
        assessments will be collected to: a) assess the incidence of adverse events, and b) evaluate
        the effect of SAR444836 on reductions in blood Phe levels and maintenance of these Phe levels
        after elimination of a Phe restricted diet.
  
        The study duration will be approximately 102 weeks (approximately 2 years) for each
        participant and includes a 6-week screening phase and 96-week follow-up period after
        SAR444836 administration.
  
        There will be a total of 41 study visits. Many study visits may occur as remote visits and be
        performed by a qualified in-home service provider.
  
        Actual study duration for an individual participant may be longer than 102 weeks due to the
        administration of SAR444836 to participants in Stage 1A in a serial fashion, or other factors
        such as delays in scheduling study visits.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of treatment-emergent adverse events (TEAEs)
  time frame: From Baseline to Week 96
  measure: Proportion of participants with sustained plasma level of Phe<360 μmol/L for ≥4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
  time frame: From Baseline to Week 96
  measure: Change from baseline in plasma level of Phe at Week 24 and Week 96 or End of Study following SAR444836 administration
  time frame: From Baseline to Week 96
  measure: Change from baseline in dietary protein intake at Week 24 and Week 96 or End of Study following SAR444836 administration
  time frame: From Baseline to Week 96
  measure: Proportion of participants with sustained plasma level of Phe <600 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
  time frame: From Baseline to Week 96
  measure: Proportion of participants with sustained plasma level of Phe <120 μmol/L for ≥ 4 weeks without dietary Phe restriction at Week 24 and Week 96 or End of Study following SAR444836 administration
  time frame: From Baseline to Week 96
  measure: Change from baseline in plasma Phe: Tyr ratio at Week 24 and Week 96 or End of Study following SAR444836 administration
  time frame: From Baseline to Week 96
  measure: Number of participants with abnormal laboratory chemistry values
  time frame: From Baseline to Week 96
  measure: Assessment of the duration of viral vector shedding of SAR444836 in sampling of urine, saliva, and semen at 4-week intervals following SAR444836 administration
  time frame: From Baseline to Week 96
  arm group label: SAR444836
  arm group type: Experimental
  description: Participants will receive a single dose of SAR444836 on Day 1
  intervention type: Drug
  intervention name: SAR444836
  description: Infusion pump, intravenous infusion (IV)
  arm group label: SAR444836
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Clinical Sciences &amp; Operations
  role: Study Director
  affiliation: Sanofi
  last name: Trial Transparency email recommended (Toll free for US &amp; Canada)
  phone: 800-633-1610
  phone ext: option 6
  email: Contact-US@sanofi.com
  facility: 
  status: Recruiting
  country: Turkey
  responsible party type: Sponsor
  mesh term: Phenylketonurias
  sharing ipd: Yes
  ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org