<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT01718041</url>
  </required_header>
  <id_info>
    <org_study_id>VRS-317 Protocol 12VR2</org_study_id>
    <nct_id>NCT01718041</nct_id>
  </id_info>
  <brief_title>Versartis Trial in Children to Assess Long-Acting Growth Hormone</brief_title>
  <acronym>VERTICAL</acronym>
  <official_title>A Long-acting Human Growth Hormone (VRS-317) in Pre-pubertal Children With Growth Hormone Deficiency: A Randomized, Open-label, Multi-center, Phase 1b/2a Study of Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Efficacy After Subcutaneous Administration for 6 Months</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Versartis Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aravive, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1b/2a study of VRS-317 (long-acting growth hormone) in pediatric patients&#xD;
      with growth hormone deficiency. During Phase 1b, pediatric patients each will receive a&#xD;
      single subcutaneous injection of VRS-317. During the Phase 2a stage, patients will receive 6&#xD;
      months of VRS-317 treatment at dose levels selected from the Phase 1b stage. The primary&#xD;
      endpoints for the study are to determine the safety and efficacy of repeat dose VRS-317.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Phase 1b, separate cohorts of patients will be tested in a single ascending dose format.&#xD;
      Safety review committee meetings will take place prior to escalating to each increasing dose&#xD;
      level. Enrolled patients will be monitored for 60 days for safety with PK/PD and safety labs&#xD;
      collected.&#xD;
&#xD;
      Two dose levels will be selected after completion of Phase 1b to be tested during Phase 2a (6&#xD;
      months of continuous VRS-317 treatment). Safety and PK assessments will be made during the&#xD;
      Phase 2a stage. Patient heights will be measured by stadiometer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</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>Phase 1b and 2a: Evaluate the safety and tolerability of multiple dosing levels of subcutaneous (SC) VRS-317 in pediatric growth hormone deficient (GHD) patients. Phase 2a: Evaluate the efficacy of multiple dose levels of VRS-317</measure>
    <time_frame>8 Months</time_frame>
    <description>Safety observations will include the number of patients with adverse events, concomitant medications, safety labs, vital signs, physical exams, single dose immunogenicity (Phase 1b), and repeat dose immunogenicity (Phase 2a).&#xD;
The primary efficacy outcome measure is the height velocity over 6 months as measured by standing height taken with stadiometer at baseline and after 6 Months of VRS-317 dosing in Phase 2a.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate pharmacokinetic measures of VRS-317.</measure>
    <time_frame>8 months</time_frame>
    <description>Secondary outcome measures include evaluation of pharmacokinetics (PK) of VRS-317 including Cmax, Tmax and AUC. PK measures will be analysed at multiple timepoints after single dosing of VRS-317 during Phase 1b and after repeat dosing of VRS-317 during Phase 2a.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluate secondary efficacy measures after 6 months of VRS-317 dosing.</measure>
    <time_frame>6 Months</time_frame>
    <description>Secondary efficacy measures during Phase 2a include change in height SDS and change in bone age after 6 months VRS-317 treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Evaluate pharmacodynamic measures</measure>
    <time_frame>8 Months</time_frame>
    <description>Secondary outcome measures include evaluation of pharmacodynamics (PD) as measured by IGF-I and IGFBP-3 responses to single dose VRS-317 during Phase 1b and as measured by IGF-I and IGFBP-3 responses to multiple doses of VRS-317 after repeat dosing during Phase 2a. PD measures will be obtained at multiple timepoints during Phase 1b and Phase 2a.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Pediatric Growth Hormone Deficiency</condition>
  <arm_group>
    <arm_group_label>VRS-317</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active treatment arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Experimental: VRS-317</intervention_name>
    <description>Active treatment arm</description>
    <arm_group_label>VRS-317</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Chronological Age ≥ 3.0 years and ≤ 11.0&#xD;
&#xD;
          -  Diagnosis of GHD as documented by GH stimulation test&#xD;
&#xD;
          -  Below average height SDS at screening&#xD;
&#xD;
          -  Appropriate weight for Stature&#xD;
&#xD;
          -  Decreased IGF-I SDS at screening&#xD;
&#xD;
          -  Delayed bone age&#xD;
&#xD;
          -  Normal thyroid function test results at screening visit&#xD;
&#xD;
          -  Legally authorized representative informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with any growth promoting agent&#xD;
&#xD;
          -  Documented history of, or current, significant disease&#xD;
&#xD;
          -  Chromosomal aneuploidy, significant gene mutations&#xD;
&#xD;
          -  Diagnosis of Attention Deficit Hyperactivity Disorder&#xD;
&#xD;
          -  Daily use of anti-inflammatory doses of glucocorticoid&#xD;
&#xD;
          -  Prior history of leukemia, lymphoma, sarcoma or cancer&#xD;
&#xD;
          -  Known allergy to constituents of the study drug formulation&#xD;
&#xD;
          -  Abnormal ocular findings at screening&#xD;
&#xD;
          -  Significant abnormality in screening laboratory studies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>11 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Clovis</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greenwood Village</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tallahassee</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Springfield</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Livingston</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sleepy Hollow</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>July 22, 2022</last_update_submitted>
  <last_update_submitted_qc>July 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Growth hormone</keyword>
  <keyword>Growth hormone deficiency</keyword>
  <keyword>Growth</keyword>
  <keyword>Pediatric growth hormone deficiency</keyword>
  <keyword>Long acting growth hormone</keyword>
  <keyword>GHD</keyword>
  <keyword>PGHD</keyword>
  <keyword>VRS 317</keyword>
  <keyword>Exten</keyword>
  <keyword>Versartis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dwarfism, Pituitary</mesh_term>
    <mesh_term>Endocrine System Diseases</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/NCT01718041
org study id: VRS-317 Protocol 12VR2
nct id: NCT01718041
lead sponsor: 
has dmc: No
This is a Phase 1b/2a study of VRS-317 (long-acting growth hormone) in pediatric patients
      with growth hormone deficiency. During Phase 1b, pediatric patients each will receive a
      single subcutaneous injection of VRS-317. During the Phase 2a stage, patients will receive 6
      months of VRS-317 treatment at dose levels selected from the Phase 1b stage. The primary
      endpoints for the study are to determine the safety and efficacy of repeat dose VRS-317.
In Phase 1b, separate cohorts of patients will be tested in a single ascending dose format.
      Safety review committee meetings will take place prior to escalating to each increasing dose
      level. Enrolled patients will be monitored for 60 days for safety with PK/PD and safety labs
      collected.

      Two dose levels will be selected after completion of Phase 1b to be tested during Phase 2a (6
      months of continuous VRS-317 treatment). Safety and PK assessments will be made during the
      Phase 2a stage. Patient heights will be measured by stadiometer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1b and 2a: Evaluate the safety and tolerability of multiple dosing levels of subcutaneous (SC) VRS-317 in pediatric growth hormone deficient (GHD) patients. Phase 2a: Evaluate the efficacy of multiple dose levels of VRS-317
time frame: 8 Months
description: Safety observations will include the number of patients with adverse events, concomitant medications, safety labs, vital signs, physical exams, single dose immunogenicity (Phase 1b), and repeat dose immunogenicity (Phase 2a).
The primary efficacy outcome measure is the height velocity over 6 months as measured by standing height taken with stadiometer at baseline and after 6 Months of VRS-317 dosing in Phase 2a.
measure: Evaluate pharmacokinetic measures of VRS-317.
time frame: 8 months
description: Secondary outcome measures include evaluation of pharmacokinetics (PK) of VRS-317 including Cmax, Tmax and AUC. PK measures will be analysed at multiple timepoints after single dosing of VRS-317 during Phase 1b and after repeat dosing of VRS-317 during Phase 2a.
measure: Evaluate secondary efficacy measures after 6 months of VRS-317 dosing.
time frame: 6 Months
description: Secondary efficacy measures during Phase 2a include change in height SDS and change in bone age after 6 months VRS-317 treatment.
measure: Evaluate pharmacodynamic measures
time frame: 8 Months
description: Secondary outcome measures include evaluation of pharmacodynamics (PD) as measured by IGF-I and IGFBP-3 responses to single dose VRS-317 during Phase 1b and as measured by IGF-I and IGFBP-3 responses to multiple doses of VRS-317 after repeat dosing during Phase 2a. PD measures will be obtained at multiple timepoints during Phase 1b and Phase 2a.
arm group label: VRS-317
arm group type: Experimental
description: Active treatment arm
intervention type: Drug
intervention name: Experimental: VRS-317
description: Active treatment arm
arm group label: VRS-317
criteria: 
gender: All
minimum age: 3 Years
maximum age: 11 Years
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Dwarfism, Pituitary
mesh term: Endocrine System Diseases