<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/NCT04480567</url>
  </required_header>
  <id_info>
    <org_study_id>307-201</org_study_id>
    <nct_id>NCT04480567</nct_id>
  </id_info>
  <brief_title>AAV Gene Therapy Study for Subjects With PKU</brief_title>
  <official_title>A Phase 1/2 Open-Label, Dose Escalation Study to Determine the Safety and Efficacy of BMN 307, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Phenylalanine Hydroxylase in Subjects With Phenylketonuria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioMarin Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioMarin Pharmaceutical</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 Phase 1/2, open-label, dose escalation study to evaluate the safety, efficacy and&#xD;
      tolerability of BMN 307 in adult PKU subjects with PAH deficiency. Participants will receive&#xD;
      a single administration of BMN 307 and will be followed for safety and efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 24, 2020</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in mean Plasma Phe levels</measure>
    <time_frame>baseline, week 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in mean Plasma Phe levels</measure>
    <time_frame>baseline, week 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in dietary protein intake from intact food</measure>
    <time_frame>baseline, week 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-emergent adverse event</measure>
    <time_frame>At 5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Phenylketonuria (PKU)</condition>
  <arm_group>
    <arm_group_label>Dose 1 of BMN 307</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2 of BMN 307</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 3 of BMN 307</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMN 307</intervention_name>
    <description>AAV Gene Therapy Infusion</description>
    <arm_group_label>Dose 1 of BMN 307</arm_group_label>
    <arm_group_label>Dose 2 of BMN 307</arm_group_label>
    <arm_group_label>Dose 3 of BMN 307</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects with diagnosis of PKU which is a condition characterized by&#xD;
             PAH deficiency&#xD;
&#xD;
          -  Ability and willingness to maintain dietary protein intake consistent with baseline&#xD;
             intake&#xD;
&#xD;
          -  Willingness to abstain from hepatotoxic substances post-BMN 307 administration&#xD;
&#xD;
          -  Willingness and capable per investigator opinion to comply with study procedures and&#xD;
             requirements&#xD;
&#xD;
          -  Willingness to use effective methods of contraception&#xD;
&#xD;
          -  Plasma Phe levels &gt; 600 µmol/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with primary BH4 deficiency or other forms of BH4 metabolism deficiency&#xD;
&#xD;
          -  Clinically significant liver dysfunction or disease&#xD;
&#xD;
          -  Prior treatment with gene therapy&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator or Sponsor, would prevent the&#xD;
             subject from fully complying with the requirements of the study&#xD;
&#xD;
          -  History of malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director, MD</last_name>
    <role>Study Director</role>
    <affiliation>BioMarin Pharmaceutical</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of South Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center - Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Birmingham NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>October 6, 2021</last_update_submitted>
  <last_update_submitted_qc>October 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PKU</keyword>
  <keyword>PAH Deficiency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phenylketonurias</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/NCT04480567
org study id: 307-201
nct id: NCT04480567
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1/2, open-label, dose escalation study to evaluate the safety, efficacy and
      tolerability of BMN 307 in adult PKU subjects with PAH deficiency. Participants will receive
      a single administration of BMN 307 and will be followed for safety and efficacy.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in mean Plasma Phe levels
time frame: baseline, week 12
measure: Change from baseline in mean Plasma Phe levels
time frame: baseline, week 96
measure: Change from baseline in dietary protein intake from intact food
time frame: baseline, week 96
measure: Number of participants with treatment-emergent adverse event
time frame: At 5 years
arm group label: Dose 1 of BMN 307
arm group type: Experimental
arm group label: Dose 2 of BMN 307
arm group type: Experimental
arm group label: Dose 3 of BMN 307
arm group type: Experimental
intervention type: Drug
intervention name: BMN 307
description: AAV Gene Therapy Infusion
arm group label: Dose 1 of BMN 307
arm group label: Dose 2 of BMN 307
arm group label: Dose 3 of BMN 307
criteria: 
gender: All
minimum age: 15 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director, MD
role: Study Director
affiliation: BioMarin Pharmaceutical
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Phenylketonurias