<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/NCT03276988</url>
  </required_header>
  <id_info>
    <org_study_id>GX30_P1/2</org_study_id>
    <nct_id>NCT03276988</nct_id>
  </id_info>
  <brief_title>Tolerability, Safety and Pharmacokinetics Study of GX-30 in Total Thyroidectomy or Near Total Thyroidectomy Patients</brief_title>
  <official_title>A Prospective, Open-label, Dose Escalation,(Phase 1); Prospective, Randomized, Evaluator Blinded, Active-controlled, 2-sequence, 2-period, 2-treatment, Crossover(Phase 2); Phase 1/2 Clinical Trial to Evaluate the Tolerability, Pharmacokinetics, Safety and Efficacy of GX-30 Administered Intramuscularly in Patients Underwent Total Thyroidectomy or Near Total Thyroidectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genexine, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Symyoo</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Genexine, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed as a combination of phase 1 (Part A) and phase 2 (Part B). The purpose&#xD;
      of Part A was to determine the safety, tolerability, and pharmacokinetics in patients with&#xD;
      total thyroidectomy or near total thyroidectomy of GX-30 and it has been completed. The Part&#xD;
      B is currently recruiting and will investigate the efficacy and safety of GX-30 compared with&#xD;
      THYROGEN®.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recombinant human TSH was developed to provide TSH stimulation without withdrawal of thyroid&#xD;
      hormone. Radioiodine ablation and diagnosis with rhTSH became the standard of care treatment&#xD;
      for patients with differentiated thyroid cancer. Stably supplying rhTSH has been the unmet&#xD;
      need for management and follow-up procedure for thyroid remnant. GX-30 is an investigational&#xD;
      product, developed to provide inexpensive rhTSH to patients in order to ensure stable supply&#xD;
      of rhTSH.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 7, 2017</start_date>
  <completion_date type="Actual">January 20, 2020</completion_date>
  <primary_completion_date type="Actual">January 20, 2020</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>Crossover Assignment</intervention_model>
    <intervention_model_description>The Part A (Phase 1) of study has been completed in which 3 single or multiple sequentially assenting doses of GX-30 were investigated. The Part B (Phase 2) is recruiting in current in which each study participant will receive the same multiple doses of GX-30 and THYROGEN® but at different period.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>At Part B, Both independent central efficacy assessors and participants will be masked. Investigators will be unmasked. (The Part A was open-label.)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy (Part B)</measure>
    <time_frame>at each Day 4, period 1 and period 2.</time_frame>
    <description>I-123 Whole body scan image classification</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TSH concentration (Part B)</measure>
    <time_frame>Baseline, Day 1 to Day 8.</time_frame>
    <description>TSH concentration for Pharmacokinetics assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADA (Part B)</measure>
    <time_frame>Baseline, Day 1 and 15 of Period 2</time_frame>
    <description>Anti-Drug Antibody detection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tg concentration (Part B)</measure>
    <time_frame>Baseline, Day 1 to Day 5</time_frame>
    <description>Thyroglobulin concentration for secondary efficacy assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T3, free T4 concentration (Part B)</measure>
    <time_frame>Baseline, Day 1, 2, 5 of each period and Day 15 of period 2.</time_frame>
    <description>Thyroid hormones concentration for pharmacodynamic assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (Part B)</measure>
    <time_frame>through study completion, average of 6 weeks.</time_frame>
    <description>Safety assessment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Total Thyroidectomy</condition>
  <condition>Near-total Thyroidectomy</condition>
  <arm_group>
    <arm_group_label>Part B - Sequence A</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Period 1 GX-30 0.9mg x 2 (Day 1 and Day 2), IM injection. Period 2 THYROGEN® 0.9mg x 2 (Day 1 and Day 2), IM injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B - Sequence B</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Period 1 THYROGEN® 0.9mg x 2 (Day 1 and Day 2), IM injection. Period 2 GX-30 0.9mg x 2 (Day 1 and Day 2), IM injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Period 1 GX-30, Period 2 THYROGEN®</intervention_name>
    <description>Part B - Sequence A. GX-30 0.9mg will be administered at Day 1 and Day 2 in Period 1. After wash-out period of 2 to 3 weeks, THYROGEN® 0.9mg will be administered in Period 2.</description>
    <arm_group_label>Part B - Sequence A</arm_group_label>
    <other_name>Thyrotropin alpha</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Period 1 THYROGEN®, Period 2 GX-30</intervention_name>
    <description>Part B - Sequence B. THYROGEN® 0.9mg will be administered at Day 1 and Day 2 in Period 1. After wash-out period of 2 to 3 weeks, GX-30 0.9mg will be administered in Period 2.</description>
    <arm_group_label>Part B - Sequence B</arm_group_label>
    <other_name>Thyrotropin alpha</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who voluntarily consented, after listing enough explanation for this study&#xD;
             and investigational product.&#xD;
&#xD;
          -  Minimum 19 years old.&#xD;
&#xD;
          -  Minimum 50kg of body weight.&#xD;
&#xD;
          -  Patients who had undergone total thyroidectomy or near total thyroidectomy due to&#xD;
             differentiated thyroid carcinoma.&#xD;
&#xD;
          -  Patient undergoing thyroid hormone administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Thyroid cancer excluding differentiated thyroid carcinoma.&#xD;
&#xD;
          -  Thyroidectomy excluding total thyroidectomy and near total thyroidectomy.&#xD;
&#xD;
          -  Patients with heart, renal, or liver failure.&#xD;
&#xD;
          -  Patients with ischemic stroke or the history of ischemic stroke.&#xD;
&#xD;
          -  Smoker or Ex-smoker with less than 3 months of stopping&#xD;
&#xD;
          -  Patients with migraine or the history of migraine.&#xD;
&#xD;
          -  Patients that the researchers do not think fit into the group, including patients&#xD;
             failed in compliance assessment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant or lactating women will be excluded. Women of childbearing potential who agreed to use a medically appropriate conceptional method till 6 months after study completion may be enrolled.</gender_description>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mu Il Kang, M.D., Ph. D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul St. Mary's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pusan National University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Suwon</city>
        <zip>16499</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <link>
    <url>https://synapse.koreamed.org/DOIx.php?id=10.7599/hmr.2012.32.4.187</url>
    <description>Park DJ. Thyroid and Hydrogen Peroxide. Hanyang Med Rev 2012;32:187-91</description>
  </link>
  <reference>
    <citation>Goel R, Raju R, Maharudraiah J, Sameer Kumar GS, Ghosh K, Kumar A, Lakshmi TP, Sharma J, Sharma R, Balakrishnan L, Pan A, Kandasamy K, Christopher R, Krishna V, Mohan SS, Harsha HC, Mathur PP, Pandey A, Keshava Prasad TS. A Signaling Network of Thyroid-Stimulating Hormone. J Proteomics Bioinform. 2011 Oct 29;4:10.4172/jpb.1000195. doi: 10.4172/jpb.1000195.</citation>
    <PMID>24255551</PMID>
  </reference>
  <reference>
    <citation>Meier CA, Braverman LE, Ebner SA, Veronikis I, Daniels GH, Ross DS, Deraska DJ, Davies TF, Valentine M, DeGroot LJ, et al. Diagnostic use of recombinant human thyrotropin in patients with thyroid carcinoma (phase I/II study). J Clin Endocrinol Metab. 1994 Jan;78(1):188-96. doi: 10.1210/jcem.78.1.8288703.</citation>
    <PMID>8288703</PMID>
  </reference>
  <reference>
    <citation>Torres MS, Ramirez L, Simkin PH, Braverman LE, Emerson CH. Effect of various doses of recombinant human thyrotropin on the thyroid radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin in normal subjects. J Clin Endocrinol Metab. 2001 Apr;86(4):1660-4. doi: 10.1210/jcem.86.4.7405.</citation>
    <PMID>11297600</PMID>
  </reference>
  <reference>
    <citation>Ladenson PW, Braverman LE, Mazzaferri EL, Brucker-Davis F, Cooper DS, Garber JR, Wondisford FE, Davies TF, DeGroot LJ, Daniels GH, Ross DS, Weintraub BD. Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma. N Engl J Med. 1997 Sep 25;337(13):888-96. doi: 10.1056/NEJM199709253371304.</citation>
    <PMID>9302303</PMID>
  </reference>
  <reference>
    <citation>Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon HR 3rd, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999 Nov;84(11):3877-85. doi: 10.1210/jcem.84.11.6094.</citation>
    <PMID>10566623</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>September 7, 2020</last_update_submitted>
  <last_update_submitted_qc>September 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thyroid cancer</keyword>
  <keyword>Thyroidectomy</keyword>
  <keyword>rhTSH</keyword>
  <keyword>GX-30</keyword>
  <patient_data>
    <sharing_ipd>No</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/NCT03276988
org study id: GX30_P1/2
nct id: NCT03276988
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is designed as a combination of phase 1 (Part A) and phase 2 (Part B). The purpose
      of Part A was to determine the safety, tolerability, and pharmacokinetics in patients with
      total thyroidectomy or near total thyroidectomy of GX-30 and it has been completed. The Part
      B is currently recruiting and will investigate the efficacy and safety of GX-30 compared with
      THYROGEN®.
Recombinant human TSH was developed to provide TSH stimulation without withdrawal of thyroid
      hormone. Radioiodine ablation and diagnosis with rhTSH became the standard of care treatment
      for patients with differentiated thyroid cancer. Stably supplying rhTSH has been the unmet
      need for management and follow-up procedure for thyroid remnant. GX-30 is an investigational
      product, developed to provide inexpensive rhTSH to patients in order to ensure stable supply
      of rhTSH.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The Part A (Phase 1) of study has been completed in which 3 single or multiple sequentially assenting doses of GX-30 were investigated. The Part B (Phase 2) is recruiting in current in which each study participant will receive the same multiple doses of GX-30 and THYROGEN® but at different period.
primary purpose: Diagnostic
masking: Double (Participant, Outcomes Assessor)
masking description: At Part B, Both independent central efficacy assessors and participants will be masked. Investigators will be unmasked. (The Part A was open-label.)
measure: Efficacy (Part B)
time frame: at each Day 4, period 1 and period 2.
description: I-123 Whole body scan image classification
measure: TSH concentration (Part B)
time frame: Baseline, Day 1 to Day 8.
description: TSH concentration for Pharmacokinetics assessment
measure: ADA (Part B)
time frame: Baseline, Day 1 and 15 of Period 2
description: Anti-Drug Antibody detection
measure: Tg concentration (Part B)
time frame: Baseline, Day 1 to Day 5
description: Thyroglobulin concentration for secondary efficacy assessment
measure: T3, free T4 concentration (Part B)
time frame: Baseline, Day 1, 2, 5 of each period and Day 15 of period 2.
description: Thyroid hormones concentration for pharmacodynamic assessment
measure: Adverse events (Part B)
time frame: through study completion, average of 6 weeks.
description: Safety assessment
arm group label: Part B - Sequence A
arm group type: Other
description: Period 1 GX-30 0.9mg x 2 (Day 1 and Day 2), IM injection. Period 2 THYROGEN® 0.9mg x 2 (Day 1 and Day 2), IM injection
arm group label: Part B - Sequence B
arm group type: Other
description: Period 1 THYROGEN® 0.9mg x 2 (Day 1 and Day 2), IM injection. Period 2 GX-30 0.9mg x 2 (Day 1 and Day 2), IM injection
intervention type: Drug
intervention name: Period 1 GX-30, Period 2 THYROGEN®
description: Part B - Sequence A. GX-30 0.9mg will be administered at Day 1 and Day 2 in Period 1. After wash-out period of 2 to 3 weeks, THYROGEN® 0.9mg will be administered in Period 2.
arm group label: Part B - Sequence A
other name: Thyrotropin alpha
intervention type: Drug
intervention name: Period 1 THYROGEN®, Period 2 GX-30
description: Part B - Sequence B. THYROGEN® 0.9mg will be administered at Day 1 and Day 2 in Period 1. After wash-out period of 2 to 3 weeks, GX-30 0.9mg will be administered in Period 2.
arm group label: Part B - Sequence B
other name: Thyrotropin alpha
criteria: 
gender: All
gender based: Yes
gender description: Pregnant or lactating women will be excluded. Women of childbearing potential who agreed to use a medically appropriate conceptional method till 6 months after study completion may be enrolled.
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Mu Il Kang, M.D., Ph. D.
role: Principal Investigator
affiliation: Seoul St. Mary's Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
url: https://synapse.koreamed.org/DOIx.php?id=10.7599/hmr.2012.32.4.187
description: Park DJ. Thyroid and Hydrogen Peroxide. Hanyang Med Rev 2012;32:187-91
citation: Goel R, Raju R, Maharudraiah J, Sameer Kumar GS, Ghosh K, Kumar A, Lakshmi TP, Sharma J, Sharma R, Balakrishnan L, Pan A, Kandasamy K, Christopher R, Krishna V, Mohan SS, Harsha HC, Mathur PP, Pandey A, Keshava Prasad TS. A Signaling Network of Thyroid-Stimulating Hormone. J Proteomics Bioinform. 2011 Oct 29;4:10.4172/jpb.1000195. doi: 10.4172/jpb.1000195.
PMID: 24255551
citation: Meier CA, Braverman LE, Ebner SA, Veronikis I, Daniels GH, Ross DS, Deraska DJ, Davies TF, Valentine M, DeGroot LJ, et al. Diagnostic use of recombinant human thyrotropin in patients with thyroid carcinoma (phase I/II study). J Clin Endocrinol Metab. 1994 Jan;78(1):188-96. doi: 10.1210/jcem.78.1.8288703.
PMID: 8288703
citation: Torres MS, Ramirez L, Simkin PH, Braverman LE, Emerson CH. Effect of various doses of recombinant human thyrotropin on the thyroid radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin in normal subjects. J Clin Endocrinol Metab. 2001 Apr;86(4):1660-4. doi: 10.1210/jcem.86.4.7405.
PMID: 11297600
citation: Ladenson PW, Braverman LE, Mazzaferri EL, Brucker-Davis F, Cooper DS, Garber JR, Wondisford FE, Davies TF, DeGroot LJ, Daniels GH, Ross DS, Weintraub BD. Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma. N Engl J Med. 1997 Sep 25;337(13):888-96. doi: 10.1056/NEJM199709253371304.
PMID: 9302303
citation: Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, Cooper DS, Graham KE, Braverman LE, Skarulis MC, Davies TF, DeGroot LJ, Mazzaferri EL, Daniels GH, Ross DS, Luster M, Samuels MH, Becker DV, Maxon HR 3rd, Cavalieri RR, Spencer CA, McEllin K, Weintraub BD, Ridgway EC. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab. 1999 Nov;84(11):3877-85. doi: 10.1210/jcem.84.11.6094.
PMID: 10566623
responsible party type: Sponsor
sharing ipd: No