<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/NCT03802201</url>
  </required_header>
  <id_info>
    <org_study_id>PTG-300-02</org_study_id>
    <nct_id>NCT03802201</nct_id>
  </id_info>
  <brief_title>Study of PTG-300 in Non-Transfusion Dependent and Transfusion-Dependent Beta-Thalassemia Subjects With Chronic Anemia</brief_title>
  <acronym>TRANSCEND</acronym>
  <official_title>A Phase 2 Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) β-Thalassemia Subjects With Chronic Anemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Protagonist Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Protagonist Therapeutics, 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 is a Phase 2 open-label, single-arm design study with dose escalation by subject cohort&#xD;
      . The study is designed to monitor the PTG-300 safety profile, to obtain preliminary evidence&#xD;
      of efficacy of PTG-300 for the treatment in β-thalassemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2 open-label, single-arm design study with dose escalation by subject cohort&#xD;
      and with the potential for individual titration (dose increase or decrease) within each&#xD;
      cohort. The study is designed to monitor the PTG-300 safety profile, to obtain preliminary&#xD;
      evidence of efficacy of PTG-300 for the treatment of chronic anemia in β-thalassemia and to&#xD;
      evaluate the appropriate dosing regimen for PTG-300 in the target population&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2018</start_date>
  <completion_date type="Actual">July 31, 2020</completion_date>
  <primary_completion_date type="Actual">July 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Multiple PTG-300 dose levels/regimens are planned to be tested for each subpopulation of β thalassemia (NTD and TD) on separate arms:&#xD;
Cohort 1: 3 mg subcutaneous (SC) weekly&#xD;
Cohort 2: 10 mg SC weekly&#xD;
Cohort 3: 20 mg SC weekly&#xD;
Cohort 4a: 40 mg SC weekly&#xD;
Cohort 4b: 40 mg SC every 2 weeks&#xD;
Cohort 7: 80 mg SC weekly&#xD;
Cohort 8: 40 mg SC twice a week&#xD;
Additional Cohorts (Cohorts 5,6,9,10, and 11) will include subjects between 12 years of age and less than 18 years of age.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>NTD: Proportion of responders at each dose</measure>
    <time_frame>4 week period</time_frame>
    <description>NTD subjects who achieve an increase in Hgb without transfusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TD: Proportion of clinical responders at each dose</measure>
    <time_frame>8 week period</time_frame>
    <description>TD subjects who achieve a reduction in red blood cell (RBC) units required over an 8 week period</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>β-thalassemia</condition>
  <condition>Ineffective Erythropoiesis</condition>
  <condition>Chronic Anemia</condition>
  <arm_group>
    <arm_group_label>PTG-300 Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: PTG-300 Subcutaneous</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PTG-300</intervention_name>
    <description>Subcutaneous (SC)</description>
    <arm_group_label>PTG-300 Active</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects aged 18 to 65 years, inclusive (Cohorts 1-4b).&#xD;
&#xD;
          2. Male and female subjects aged 12-&lt;18 years, with a minimum weight of 30 kg (Cohorts 5&#xD;
             and 6).&#xD;
&#xD;
          3. Documented diagnosis of β-thalassemia with no other Hgb abnormality.&#xD;
&#xD;
        Inclusion criteria applicable only for NTD β-thalassemia subjects:&#xD;
&#xD;
          1. Mean Hgb &lt; 10.0 g/dL of two measurements (one performed 7-28 days prior to dosing and&#xD;
             the other performed within 7 days prior to dosing).&#xD;
&#xD;
          2. Requirement of &lt; 6 units RBC transfusion in a 24 week period with the last transfusion&#xD;
             at least 8 weeks before screening.&#xD;
&#xD;
        Inclusion criteria applicable only for TD β-thalassemia subjects:&#xD;
&#xD;
          1. Transfusion requirement of at least 6 units of RBC in the 24 weeks prior to screening&#xD;
             with no transfusion free period &gt; 45 days.&#xD;
&#xD;
          2. Last RBC transfusion 5-10 days prior to dosing.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with Sickle Cell disease, Hgb H, Hb Bart's hydrops foetalis or hemoglobin S&#xD;
&#xD;
          2. Infection requiring hospitalization or IV antimicrobial therapy, or opportunistic&#xD;
             infection within 6 months of dosing, any infection requiring antimicrobial therapy&#xD;
             within 2 weeks of dosing; history of infection with human immunodeficiency virus&#xD;
             (HIV).&#xD;
&#xD;
          3. Subject has a concurrent clinically significant, unstable or uncontrolled&#xD;
             cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary,&#xD;
             hematological, coagulation, immunological, endocrine/metabolic or other medical&#xD;
             disorder that, in the opinion of the Investigator, might confound the results of the&#xD;
             study or pose additional risk to the subject by their participation in the study.&#xD;
&#xD;
          4. Known primary or secondary immunodeficiency.&#xD;
&#xD;
          5. History within 6 months of screening of any of the following:&#xD;
&#xD;
             myocardial infarction, unstable angina, transient ischemic attack, decompensated heart&#xD;
             failure requiring hospitalization, congestive heart failure (New York Heart&#xD;
             Association Class 3 or 4), uncontrolled arrhythmias, cardiac revascularization,&#xD;
             stroke, uncontrolled hypertension (resting systolic blood pressure [BP] &gt; 160mmHg or&#xD;
             resting diastolic BP &gt; 100mmHg on more than one occasion) or uncontrolled diabetes&#xD;
             (Hgb A1c &gt; 9% or &gt; one episode of severe hypoglycemia).&#xD;
&#xD;
          6. Pregnant or lactating females.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of The University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Patras</name>
      <address>
        <city>Patras</city>
        <state>Achaia</state>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laiko General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>11562</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Athens General Hospital 'G Gennimatas'</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hippokration Hospital</name>
      <address>
        <city>Thessaloníki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presidio Ospedaliero Antonio Perrino</name>
      <address>
        <city>Brindisi</city>
        <zip>72100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU dell'Università degli Studi della Campania Luigi Vanvitelli</name>
      <address>
        <city>Napoli</city>
        <zip>80138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chronic Care Center</name>
      <address>
        <city>Beirut</city>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ampang</name>
      <address>
        <city>Ampang</city>
        <zip>68000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pulau Pinang</name>
      <address>
        <city>George Town</city>
        <zip>10990</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sultanah Aminah</name>
      <address>
        <city>Johor Bahru</city>
        <zip>80100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Kota Kinabalu</city>
        <zip>88586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Umum Sarawak</name>
      <address>
        <city>Kuching</city>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chulalongkorn University</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siriraj Hospital Mahidol University</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maharaj Nakorn Chiang Mai Chiang Mai University</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Khon Kaen University</name>
      <address>
        <city>Khon Kaen</city>
        <zip>40002</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Naresuan University</name>
      <address>
        <city>Phitsanulok</city>
        <zip>65000</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Farhat Hached</name>
      <address>
        <city>Sousse</city>
        <zip>4000</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bone Marrow Transplant Center</name>
      <address>
        <city>Tunis</city>
        <zip>1006</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aziza Othmana Hospital</name>
      <address>
        <city>Tunis</city>
        <zip>1008</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal Military Hospital</name>
      <address>
        <city>Tunis</city>
        <zip>1089</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acibadem Adana Hospital</name>
      <address>
        <city>Adana</city>
        <zip>01130</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe University Medical Faculty</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akdeniz Universitesi Hastanesi</name>
      <address>
        <city>Antalya</city>
        <zip>07059</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi</name>
      <address>
        <city>Istanbul</city>
        <zip>34093</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege Universitesi Tip Fakultesi</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mersin University Medical Facult</name>
      <address>
        <city>Mersin</city>
        <zip>33343</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <zip>E1 1BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>Italy</country>
    <country>Lebanon</country>
    <country>Malaysia</country>
    <country>Thailand</country>
    <country>Tunisia</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <disposition_first_submitted>July 9, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>July 13, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">July 16, 2021</disposition_first_posted>
  <last_update_submitted>July 13, 2021</last_update_submitted>
  <last_update_submitted_qc>July 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic anemia</keyword>
  <keyword>β-thalassemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03802201
org study id: PTG-300-02
nct id: NCT03802201
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2 open-label, single-arm design study with dose escalation by subject cohort
      . The study is designed to monitor the PTG-300 safety profile, to obtain preliminary evidence
      of efficacy of PTG-300 for the treatment in β-thalassemia.
This is a Phase 2 open-label, single-arm design study with dose escalation by subject cohort
      and with the potential for individual titration (dose increase or decrease) within each
      cohort. The study is designed to monitor the PTG-300 safety profile, to obtain preliminary
      evidence of efficacy of PTG-300 for the treatment of chronic anemia in β-thalassemia and to
      evaluate the appropriate dosing regimen for PTG-300 in the target population
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Multiple PTG-300 dose levels/regimens are planned to be tested for each subpopulation of β thalassemia (NTD and TD) on separate arms:
Cohort 1: 3 mg subcutaneous (SC) weekly
Cohort 2: 10 mg SC weekly
Cohort 3: 20 mg SC weekly
Cohort 4a: 40 mg SC weekly
Cohort 4b: 40 mg SC every 2 weeks
Cohort 7: 80 mg SC weekly
Cohort 8: 40 mg SC twice a week
Additional Cohorts (Cohorts 5,6,9,10, and 11) will include subjects between 12 years of age and less than 18 years of age.
primary purpose: Treatment
masking: None (Open Label)
measure: NTD: Proportion of responders at each dose
time frame: 4 week period
description: NTD subjects who achieve an increase in Hgb without transfusion
measure: TD: Proportion of clinical responders at each dose
time frame: 8 week period
description: TD subjects who achieve a reduction in red blood cell (RBC) units required over an 8 week period
arm group label: PTG-300 Active
arm group type: Experimental
description: Drug: PTG-300 Subcutaneous
intervention type: Drug
intervention name: PTG-300
description: Subcutaneous (SC)
arm group label: PTG-300 Active
criteria: 
gender: All
minimum age: 12 Years
maximum age: 65 Years
healthy volunteers: No
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country: Greece
country: Italy
country: Lebanon
country: Malaysia
country: Thailand
country: Tunisia
country: Turkey
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Anemia
mesh term: Thalassemia
mesh term: beta-Thalassemia