<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/NCT03767270</url>
  </required_header>
  <id_info>
    <org_study_id>MRT5201-101</org_study_id>
    <secondary_id>2018-004095-35</secondary_id>
    <nct_id>NCT03767270</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and PK/PD Evaluation of Intravenous Administration of MRT5201 in Patients With OTC Deficiency</brief_title>
  <acronym>STEP-OTC</acronym>
  <official_title>A Phase 1/2 Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered MRT5201 in Subjects With Ornithine Transcarbamylase Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Translate Bio, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Translate Bio, Inc.</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 Phase 1/2, first-in-human study will evaluate the safety and tolerability of single&#xD;
      escalating doses of MRT5201 administered intravenously to subjects with OTC Deficiency&#xD;
      (OTCD). This study will also evaluate the effect of a single dose of MRT5201 on metabolic&#xD;
      markers of OTCD and ureagenesis; and determine an acceptable dosing interval of MRT5201.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Program was discontinued.&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2019</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2022</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>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of treatment-emergent adverse events by treatment group</measure>
    <time_frame>Week 24</time_frame>
    <description>The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) for each dosing cohort by treatment group, assessed by severity and relationship to study product.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics parameters of MRT5201</measure>
    <time_frame>1 month after single dose</time_frame>
    <description>Pharmacokinetics of MRT5201 as measured by levels of mRNA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of a single dose of MRT5201 on ureagenesis</measure>
    <time_frame>Up to 1 month after single dose</time_frame>
    <description>Change from Baseline in 4-hour ureagenesis AUC at weeks 2, 3, 4, and 5 after a single dose of MRT5201</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of single dose of MRT5201 on metabolic markers of OTCD</measure>
    <time_frame>6 months after single dose</time_frame>
    <description>Change from Baseline in 8-hour ammonia AUC</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Ornithine Transcarbamylase Deficiency</condition>
  <arm_group>
    <arm_group_label>MRT5201</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Ascending Low, Mid, and High doses of MRT5201</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo comparator using 5% dextrose in water at the same administration rate as study drug.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MRT5201</intervention_name>
    <description>Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles</description>
    <arm_group_label>MRT5201</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>5% dextrose in water</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a documented diagnosis of OTCD.&#xD;
&#xD;
          -  Documented history of ≥1 symptomatic hyperammonemia event with ammonia ≥100 µmol/L&#xD;
&#xD;
          -  Subject's OTCD is stable as evidenced by meeting the following criteria:&#xD;
&#xD;
               -  Ammonia level &lt;175 µmol/L during the Screening Period and at Baseline (Day -1)&#xD;
&#xD;
               -  No clinical symptoms of hyperammonemia during the Screening Period and at&#xD;
                  Baseline (Day -1)&#xD;
&#xD;
          -  If using nitrogen scavenger therapy, must be on a stable regimen for ≥28 days prior to&#xD;
             signing informed consent&#xD;
&#xD;
          -  Subject has maintained a stable protein restricted diet (which may or may not include&#xD;
             medical foods) and/or amino acid supplementation with no changes in calorie or protein&#xD;
             goals and no changes in medical food and/or amino acid supplementation for ≥ 28 days&#xD;
             prior to signing informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any laboratory abnormality that may put the subject at increased risk by participating&#xD;
             in this study.&#xD;
&#xD;
          -  Have any significant concurrent or past medical condition that would represent an&#xD;
             unacceptable risk to the subject or might jeopardize the collection of high-quality&#xD;
             data from the study. These include but are not limited to:&#xD;
&#xD;
               -  History of liver transplant, including hepatocyte therapy/transplant&#xD;
&#xD;
               -  History of liver disease&#xD;
&#xD;
               -  Positive viral serology test results for HIV type 1 or 2 antibodies, hepatitis B&#xD;
                  surface antigen (HBsAg) or hepatitis C virus (HCV) antibody&#xD;
&#xD;
               -  Type I or Type II diabetes that is poorly controlled, in the opinion of the&#xD;
                  Investigator&#xD;
&#xD;
               -  Poorly controlled hypertension (defined as systolic blood pressure [BP] &gt; 150 mm&#xD;
                  Hg or diastolic BP &gt; 90 mm Hg)&#xD;
&#xD;
               -  Use of anticoagulants or platelet inhibitors, including but not limited to&#xD;
                  heparin and non-steroidal anti-inflammatory drugs (NSAIDS). Acetaminophen is&#xD;
                  permitted&#xD;
&#xD;
          -  Participation in previous clinical studies evaluating investigational OTCD therapies&#xD;
             directed at expressing functional OTC protein (eg, OTC gene therapy studies, other&#xD;
             mRNA replacement therapy) that has led to the presence of anti-OTC antibodies.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>September 12, 2019</last_update_submitted>
  <last_update_submitted_qc>September 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>OTC</keyword>
  <keyword>Urea Cycle Disorder</keyword>
  <keyword>UCD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ornithine Carbamoyltransferase Deficiency Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03767270
org study id: MRT5201-101
secondary id: 2018-004095-35
nct id: NCT03767270
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This Phase 1/2, first-in-human study will evaluate the safety and tolerability of single
      escalating doses of MRT5201 administered intravenously to subjects with OTC Deficiency
      (OTCD). This study will also evaluate the effect of a single dose of MRT5201 on metabolic
      markers of OTCD and ureagenesis; and determine an acceptable dosing interval of MRT5201.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The incidence of treatment-emergent adverse events by treatment group
time frame: Week 24
description: The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) for each dosing cohort by treatment group, assessed by severity and relationship to study product.
measure: Pharmacokinetics parameters of MRT5201
time frame: 1 month after single dose
description: Pharmacokinetics of MRT5201 as measured by levels of mRNA
measure: Effect of a single dose of MRT5201 on ureagenesis
time frame: Up to 1 month after single dose
description: Change from Baseline in 4-hour ureagenesis AUC at weeks 2, 3, 4, and 5 after a single dose of MRT5201
measure: Effect of single dose of MRT5201 on metabolic markers of OTCD
time frame: 6 months after single dose
description: Change from Baseline in 8-hour ammonia AUC
arm group label: MRT5201
arm group type: Experimental
description: Single Ascending Low, Mid, and High doses of MRT5201
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo comparator using 5% dextrose in water at the same administration rate as study drug.
intervention type: Biological
intervention name: MRT5201
description: Codon-optimized human ornithine transcarbamylase messenger ribonucleic acid with lipid-based nanoparticles
arm group label: MRT5201
intervention type: Other
intervention name: Placebo
description: 5% dextrose in water
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Ornithine Carbamoyltransferase Deficiency Disease
sharing ipd: Undecided