<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/NCT03305016</url>
  </required_header>
  <id_info>
    <org_study_id>TransCon hGH CT-302</org_study_id>
    <secondary_id>U1111-1199-8218</secondary_id>
    <nct_id>NCT03305016</nct_id>
  </id_info>
  <brief_title>A Safety, Tolerability and Efficacy Study of TransCon hGH in Children With Growth Hormone Deficiency</brief_title>
  <official_title>fliGHt: A Multicenter, Phase 3, Open-Label, 26-Week Trial Investigating the Safety, Tolerability and Efficacy of TransCon hGH Administered Once Weekly in Children With GHD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ascendis Pharma Endocrinology Division A/S</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ascendis Pharma A/S</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>
      A 26 week trial of TransCon hGH, a long-acting growth hormone product, administered&#xD;
      once-a-week. Approximately 150 children (males and females) with growth hormone deficiency&#xD;
      (GHD) will be included. All study participants will receive TransCon hGH. This is a global&#xD;
      trial that will be conducted in, but not limited to, the United States, Canada, Australia,&#xD;
      and New Zealand.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 13, 2017</start_date>
  <completion_date type="Actual">March 19, 2019</completion_date>
  <primary_completion_date type="Actual">March 19, 2019</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>All study participants will receive TransCon hGH</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]</measure>
    <time_frame>26 weeks</time_frame>
    <description>Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment</measure>
    <time_frame>26 weeks</time_frame>
    <description>Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment</measure>
    <time_frame>26 weeks</time_frame>
    <description>IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment</measure>
    <time_frame>Baseline and 26 weeks</time_frame>
    <description>Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation</measure>
    <time_frame>26 weeks</time_frame>
    <description>Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">146</enrollment>
  <condition>Growth Hormone Deficiency, Pediatric</condition>
  <condition>Endocrine System Diseases</condition>
  <condition>Hormone Deficiency</condition>
  <condition>Pituitary Diseases</condition>
  <arm_group>
    <arm_group_label>TransCon hGH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once weekly subcutaneous injection of TransCon hGH</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TransCon hGH</intervention_name>
    <description>Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week</description>
    <arm_group_label>TransCon hGH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Investigator-determined GHD diagnosis prior to the historical initiation of daily hGH&#xD;
             therapy.&#xD;
&#xD;
          2. 6 months to 17 years old, inclusive, at Visit 1&#xD;
&#xD;
               1. If 3 to 17 years old, are taking daily hGH at a dose of ≥ 0.20 mg hGH/kg/week for&#xD;
                  at least 13 weeks but no more than 130 weeks prior to Visit 1&#xD;
&#xD;
               2. If ≥ 6 months but &lt; 3 years old, are either hGH treatment-naïve or are taking&#xD;
                  daily hGH at a dose of ≥ 0.20mg hGH/kg/week for no more than 130 weeks prior to&#xD;
                  Visit 1&#xD;
&#xD;
          3. Tanner stage &lt; 5 at Visit 1&#xD;
&#xD;
          4. Open epiphyses (bone age ≤14.0 years for females or ≤16.0 years for males)&#xD;
&#xD;
          5. Written, signed, informed consent of the parent or legal guardian of the subject and&#xD;
             written assent of the subject as required by the IRB/HREC/IEC&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Weight of &lt; 5.5 kg or &gt; 80 kg at Visit 1&#xD;
&#xD;
          2. Females of child-bearing potential&#xD;
&#xD;
          3. History of malignant disease&#xD;
&#xD;
          4. Any clinically significant abnormality likely to affect growth or the ability to&#xD;
             evaluate growth (eg, chronic diseases or conditions such as renal insufficiency,&#xD;
             spinal cord irradiation, hypothyroidism, active celiac disease, malnutrition or&#xD;
             psychosocial dwarfism)&#xD;
&#xD;
          5. Poorly-controlled diabetes mellitus (HbA1c &gt;8.0%) or diabetic complications&#xD;
&#xD;
          6. Known neutralizing antibodies against hGH&#xD;
&#xD;
          7. Major medical conditions, unless approved by Medical Monitor&#xD;
&#xD;
          8. Pregnancy&#xD;
&#xD;
          9. Presence of contraindications to hGH treatment&#xD;
&#xD;
         10. Likely to be non-compliant with respect to trial conduct (in regards to the subject&#xD;
             and/or the parent/legal guardian/caregiver)&#xD;
&#xD;
         11. Participation in any other trial of an investigational agent within 30 days prior to&#xD;
             Visit 1&#xD;
&#xD;
         12. Prior exposure to investigational hGH&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aimee D Shu, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ascendis Pharma, Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David B Karpf, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ascendis Pharma, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neufeld Medical Group Inc.</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center of Excellence in Diabetes and Endocrinology</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Pediatric Endocrinology</name>
      <address>
        <city>Centennial</city>
        <state>Colorado</state>
        <zip>80112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Health System</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando Health Inc.</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tallahassee Memorial Hospital</name>
      <address>
        <city>Tallahassee</city>
        <state>Florida</state>
        <zip>32308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Minnesota</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Winthrop Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Diabetes and Endocrine Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cook Children's Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Children's Hospital</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of The King's Daughters</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Children's Hospital</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stollery Children's Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Liggins Institute, The University of Auckland</name>
      <address>
        <city>Grafton</city>
        <state>Auckland</state>
        <zip>1023</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>New Zealand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>October 4, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <results_first_submitted>September 24, 2021</results_first_submitted>
  <results_first_submitted_qc>December 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 4, 2022</results_first_posted>
  <disposition_first_submitted>February 18, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>December 7, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 4, 2022</disposition_first_posted>
  <last_update_submitted>December 7, 2021</last_update_submitted>
  <last_update_submitted_qc>December 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Human Growth Hormone</keyword>
  <keyword>hGH</keyword>
  <keyword>GHD</keyword>
  <keyword>rhGH</keyword>
  <keyword>Pediatric Growth Hormone Deficiency</keyword>
  <keyword>Long Acting Growth Hormone</keyword>
  <keyword>Somatropin</keyword>
  <keyword>Prodrug</keyword>
  <keyword>Growth Failure</keyword>
  <keyword>Growth Hormone Replacement Therapy</keyword>
  <keyword>Sustained Release Growth Hormone</keyword>
  <keyword>Growth Hormone Deficiency</keyword>
  <keyword>TransCon GH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dwarfism, Pituitary</mesh_term>
    <mesh_term>Pituitary Diseases</mesh_term>
    <mesh_term>Endocrine System Diseases</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT03305016/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 14, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT03305016/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 162 subjects were screened for entry into this trial; of these, 16 subjects did not meet eligibility criteria and were considered screen failures.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Lonapegsomatropin</title>
          <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="146"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="144"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lonapegsomatropin</title>
          <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="146"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.6" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age, Categorical:</title>
              <category_list>
                <category>
                  <title>&lt;3 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥3 and &lt;6 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥6 to &lt;11 years (girls) or ≥6 to &lt;12 years (boys)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥11 years (girls) or ≥12 years (boys)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="132.4" spread="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height SDS</title>
          <description>Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean.</description>
          <units>standard deviation score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-1.42" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.3" spread="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.5" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>IGF-1 SDS</title>
          <description>IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.</description>
          <units>standard deviation score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.85" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]</title>
        <description>Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment</description>
        <time_frame>26 weeks</time_frame>
        <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lonapegsomatropin</title>
            <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]</title>
          <description>Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment</description>
          <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="146"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Related Serious TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment</title>
        <description>Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.</description>
        <time_frame>26 weeks</time_frame>
        <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lonapegsomatropin</title>
            <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment</title>
          <description>Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.</description>
          <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
          <units>cm/year</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.72" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment</title>
        <description>IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.</description>
        <time_frame>26 weeks</time_frame>
        <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lonapegsomatropin</title>
            <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment</title>
          <description>IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.</description>
          <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment</title>
        <description>Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.</description>
        <time_frame>Baseline and 26 weeks</time_frame>
        <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lonapegsomatropin</title>
            <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment</title>
          <description>Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.</description>
          <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
          <units>standard deviation score</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="144"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation</title>
        <description>Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.</description>
        <time_frame>26 weeks</time_frame>
        <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lonapegsomatropin</title>
            <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation</title>
          <description>Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.</description>
          <population>The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="145"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>26 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lonapegsomatropin</title>
          <description>Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="146"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="65" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="146"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="146"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Aimee D Shu, MD</name_or_title>
      <organization>Ascendis Pharma, Inc.</organization>
      <phone>+1 650 352 8389</phone>
      <email>ADS@ascendispharma.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03305016
org study id: TransCon hGH CT-302
secondary id: U1111-1199-8218
nct id: NCT03305016
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A 26 week trial of TransCon hGH, a long-acting growth hormone product, administered
      once-a-week. Approximately 150 children (males and females) with growth hormone deficiency
      (GHD) will be included. All study participants will receive TransCon hGH. This is a global
      trial that will be conducted in, but not limited to, the United States, Canada, Australia,
      and New Zealand.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: All study participants will receive TransCon hGH
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
time frame: 26 weeks
description: Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment
measure: Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment
time frame: 26 weeks
description: Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.
measure: Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment
time frame: 26 weeks
description: IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.
measure: Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment
time frame: Baseline and 26 weeks
description: Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.
measure: Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
time frame: 26 weeks
description: Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.
arm group label: TransCon hGH
arm group type: Experimental
description: Once weekly subcutaneous injection of TransCon hGH
intervention type: Drug
intervention name: TransCon hGH
description: Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week
arm group label: TransCon hGH
criteria: 
gender: All
minimum age: 6 Months
maximum age: 17 Years
healthy volunteers: No
last name: Aimee D Shu, MD
role: Study Director
affiliation: Ascendis Pharma, Inc.
last name: David B Karpf, MD
role: Study Director
affiliation: Ascendis Pharma, Inc.
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country: Australia
country: Canada
country: New Zealand
country: United States
responsible party type: Sponsor
mesh term: Dwarfism, Pituitary
mesh term: Pituitary Diseases
mesh term: Endocrine System Diseases
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 