<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/NCT04411082</url>
  </required_header>
  <id_info>
    <org_study_id>IMR-BTL-201</org_study_id>
    <secondary_id>2019-002989-12</secondary_id>
    <nct_id>NCT04411082</nct_id>
  </id_info>
  <brief_title>A Study of IMR-687 in Subjects With Beta Thalassemia</brief_title>
  <official_title>A Phase 2 Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects With Beta Thalassemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imara, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imara, 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>
      A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety,&#xD;
      tolerability, PK, and PD of IMR-687 (phosphodiesterase (PDE) 9 inhibitor) administered once&#xD;
      daily (qd) orally for 36 weeks in 2 populations of adult subjects with β-thalassemia:&#xD;
      Population 1 (Transfusion Dependent Thalassemia (TDT) subjects) and Population 2&#xD;
      (Non-Transfusion Dependent Thalassemia (NTDT) subjects).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    IMR-BTL-201demonstrated that while IMR-687 was generally well-tolerated, it failed to show any&#xD;
    meaningful benefit in transfusion burden or improvement in most disease-related biomarkers. So,&#xD;
    the sponsor has decided to discontinue this study&#xD;
  </why_stopped>
  <start_date type="Actual">October 16, 2020</start_date>
  <completion_date type="Actual">May 4, 2022</completion_date>
  <primary_completion_date type="Actual">March 11, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Double-Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>IMR-687 Safety and Tolerability</measure>
    <time_frame>Baseline to Week 40</time_frame>
    <description>Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 in the absence of transfusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NTDT Patients: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 12 to Week 24 in Absence of Transfusions</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 24 to Week 36 in the absence of transfusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions</measure>
    <time_frame>Baseline to Week 36</time_frame>
    <description>Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>β Thalassemia</condition>
  <arm_group>
    <arm_group_label>Lower Dose IMR-687</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of once daily IMR-687</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Higher dose IMR-687</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of once daily IMR-687</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral administration of once daily placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMR-687</intervention_name>
    <description>Oral administration of once daily IMR-687</description>
    <arm_group_label>Higher dose IMR-687</arm_group_label>
    <arm_group_label>Lower Dose IMR-687</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration of once daily Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Documented diagnosis of β-thalassemia or HbE/ β-thalassemia in their medical history.&#xD;
             Concomitant alpha gene deletion, duplication, or triplication is allowed.&#xD;
&#xD;
          2. Documentation of the dates of transfusion events and the number of all pRBC units per&#xD;
             event within the 12 weeks prior to the Baseline (Day 1) visit. .&#xD;
&#xD;
          3. Must be willing and able to complete all study assessments and procedures, and to&#xD;
             communicate effectively with the investigator and site staff.&#xD;
&#xD;
          4. TDT Subjects: subjects must be regularly transfused, defined as &gt;3 to 10 pRBC units in&#xD;
             the12 weeks prior to Baseline (Day 1) visit and no transfusion-free period for &gt;35&#xD;
             days during that period.&#xD;
&#xD;
          5. NTDT subjects: Subjects must be transfusion independent, defined as 0 to ≤3 units of&#xD;
             pRBCs received during the 12-week period prior to the Baseline (Day 1) visit, must not&#xD;
             be on a regular transfusion program, must be RBC transfusion-free for at least ≥ 4&#xD;
             weeks prior to randomization, and must not be scheduled to start a regular&#xD;
&#xD;
          6. hematopoietic stem cell transplantation within 9 months.&#xD;
&#xD;
          7. NTDT subjects: Subjects must have Hb ≤10.0 g/dL at Screening; the screening Hb sample&#xD;
             must be collected 7 to 28 days prior to randomization. Hb values within 21 days&#xD;
             post-transfusion will be excluded.&#xD;
&#xD;
          8. ECOG performance score of 0 to 1&#xD;
&#xD;
          9. Female subjects must not be pregnant, or breastfeeding and be highly unlikely to&#xD;
             become pregnant. Male subjects must be unlikely to impregnate a partner.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of α-thalassemia (e.g., hemoglobin H [HbH]) or hemoglobin S (HbS)/ β&#xD;
             thalassemia.&#xD;
&#xD;
          2. Body mass index (BMI) &lt;17.0 kg/m2 or a total body weight &lt;45 kg; or BMI &gt;35 kg/m2&#xD;
&#xD;
          3. Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or&#xD;
             acute event of malaria, or who are known to be positive for human immunodeficiency&#xD;
             virus (HIV).&#xD;
&#xD;
          4. Stroke requiring medical intervention ≤24 weeks prior to randomization.&#xD;
&#xD;
          5. Platelet count &gt;1000 × 109/L.&#xD;
&#xD;
          6. Participated in another clinical study of an investigational agent (or device) within&#xD;
             30 days or 5-half-lives of date of informed consent, whichever is longer, or is&#xD;
             currently participating in another study.&#xD;
&#xD;
          7. For Subjects on iron chelation therapy (ICT) at the time of ICF signing, initiation of&#xD;
             ICT less than 24 weeks before the predicted randomization date.&#xD;
&#xD;
          8. Prior exposure to sotatercept or luspatercept, IMR-687, or gene therapy within 6&#xD;
             months prior to randomization (Day 1).&#xD;
&#xD;
          9. Subjects who have major organ damage&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steve Luperchio</last_name>
    <role>Study Director</role>
    <affiliation>Cardurion Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Herlev Hospital</name>
      <address>
        <city>Herlev</city>
        <state>Hovedstaden</state>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire du Cancer de Toulouse Oncopole</name>
      <address>
        <city>Toulouse cedex 9</city>
        <state>Haute-Garonn</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon Cedex 03</city>
        <state>Rhone</state>
        <zip>69437</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker-Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M. Zodelava Hematology Centre</name>
      <address>
        <city>Tbilisi</city>
        <state>Borjomi</state>
        <zip>0112</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Center of Surgery</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medinvest - Institute of Hematology and Transfusiology</name>
      <address>
        <city>Tbilisi</city>
        <zip>0186</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aghia Sofia General Children's Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laiko General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ippokrateio General Hospital of Thessaloniki</name>
      <address>
        <city>Thessaloníki</city>
        <state>Central Macedonia</state>
        <zip>54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Patras</name>
      <address>
        <city>Patra</city>
        <state>Peloponnese</state>
        <zip>26504</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Health Care Campus</name>
      <address>
        <city>Haifa</city>
        <state>Haifa District</state>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah University Hospital Ein Kerem</name>
      <address>
        <city>Jerusalem</city>
        <state>Jerusalem District</state>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Galilee Medical Center</name>
      <address>
        <city>Nahariya</city>
        <state>Northern District</state>
        <zip>2210001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emek Medical Center</name>
      <address>
        <city>Afula</city>
        <zip>18101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Giuseppe Brotzu</name>
      <address>
        <city>Orbassano</city>
        <state>Turin</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli</name>
      <address>
        <city>Orbassano</city>
        <state>Turin</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chronic Care Center</name>
      <address>
        <city>Hazmiyeh</city>
        <zip>213</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sultanah Aminah Johor Bharu</name>
      <address>
        <city>Johor Bahru</city>
        <state>Johor</state>
        <zip>80100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sultanah Bahiyah</name>
      <address>
        <city>Alor Setar</city>
        <state>Kedah</state>
        <zip>05460</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pulau Pinang</name>
      <address>
        <city>George Town</city>
        <state>Penang</state>
        <zip>10450</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Raja Permaisuri Bainun</name>
      <address>
        <city>Ipoh</city>
        <state>Perak</state>
        <zip>30450</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Queen Elizabeth - Kota Kinabalu</name>
      <address>
        <city>Kota Kinabalu</city>
        <state>Sabah</state>
        <zip>88586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Umum Sarawak</name>
      <address>
        <city>Kuching</city>
        <state>Sarawak</state>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital d'Enfants Rabat</name>
      <address>
        <city>Rabat</city>
        <zip>10100</zip>
        <country>Morocco</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam Universitair Medische Centra - Academisch Medisch Centrum</name>
      <address>
        <city>Amsterdam</city>
        <state>North Holland</state>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hôpital Universitaire Farhat Hached</name>
      <address>
        <city>Sousse</city>
        <zip>4000</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre National de Greffe de la Moelle Osseuse</name>
      <address>
        <city>Tunis</city>
        <zip>1006</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Aziza Othmana</name>
      <address>
        <city>Tunis</city>
        <zip>1008</zip>
        <country>Tunisia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akdeniz Üniversitesi</name>
      <address>
        <city>Mersin</city>
        <state>Icel</state>
        <zip>33110</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mersin Üniversitesi Tıp Fakültesi</name>
      <address>
        <city>Mersin</city>
        <state>Icel</state>
        <zip>33110</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe Üniversitesi</name>
      <address>
        <city>Ankara</city>
        <zip>06230</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>Whittington Health NHS Trust</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>N19 5NF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester University NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <state>England</state>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>France</country>
    <country>Georgia</country>
    <country>Greece</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Lebanon</country>
    <country>Malaysia</country>
    <country>Morocco</country>
    <country>Netherlands</country>
    <country>Tunisia</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>April 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <results_first_submitted>June 6, 2022</results_first_submitted>
  <results_first_submitted_qc>June 6, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 30, 2022</results_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Transfusion</keyword>
  <keyword>TDT</keyword>
  <keyword>NTDT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</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>March 15, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT04411082/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>October 14, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT04411082/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TDT High Dose</title>
          <description>TDT High dose</description>
        </group>
        <group group_id="P2">
          <title>TDT Low Dose</title>
          <description>TDT Low dose</description>
        </group>
        <group group_id="P3">
          <title>TDT Placebo</title>
          <description>TDT Placebo</description>
        </group>
        <group group_id="P4">
          <title>NTDT High Dose</title>
          <description>NTDT High dose</description>
        </group>
        <group group_id="P5">
          <title>NTDT Low Dose</title>
          <description>NTDT Low dose</description>
        </group>
        <group group_id="P6">
          <title>NTDT Placebo</title>
          <description>NTDT Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="20"/>
                <participants group_id="P4" count="24"/>
                <participants group_id="P5" count="12"/>
                <participants group_id="P6" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="16"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set</population>
      <group_list>
        <group group_id="B1">
          <title>TDT High Dose</title>
          <description>TDT High dose</description>
        </group>
        <group group_id="B2">
          <title>TDT Low Dose</title>
          <description>TDT Low dose</description>
        </group>
        <group group_id="B3">
          <title>TDT Placebo</title>
          <description>TDT Placebo</description>
        </group>
        <group group_id="B4">
          <title>NTDT High Dose</title>
          <description>NTDT High dose</description>
        </group>
        <group group_id="B5">
          <title>NTDT Low Dose</title>
          <description>NTDT Low dose</description>
        </group>
        <group group_id="B6">
          <title>NTDT Placebo</title>
          <description>NTDT Placebo</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="20"/>
            <count group_id="B4" value="24"/>
            <count group_id="B5" value="12"/>
            <count group_id="B6" value="12"/>
            <count group_id="B7" value="122"/>
          </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="31.7" spread="12.06"/>
                    <measurement group_id="B2" value="30.0" spread="9.95"/>
                    <measurement group_id="B3" value="31.3" spread="8.57"/>
                    <measurement group_id="B4" value="34.1" spread="12.64"/>
                    <measurement group_id="B5" value="28.5" spread="8.21"/>
                    <measurement group_id="B6" value="36.0" spread="9.56"/>
                    <measurement group_id="B7" value="31.9" spread="10.69"/>
                  </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="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Malaysia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Greece</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lebanon</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Netherlands</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Turkey</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Morocco</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Georgia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Israel</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tunisia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.900" spread="3.2252"/>
                    <measurement group_id="B2" value="21.252" spread="2.2874"/>
                    <measurement group_id="B3" value="22.699" spread="2.9968"/>
                    <measurement group_id="B4" value="22.031" spread="3.5415"/>
                    <measurement group_id="B5" value="21.1320" spread="3.5047"/>
                    <measurement group_id="B6" value="21.9120" spread="3.5638"/>
                    <measurement group_id="B7" value="22.0873" spread="3.1573"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Serum Ferritin</title>
          <units>micrograms per liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1724.4" spread="1857.66"/>
                    <measurement group_id="B2" value="3449.1" spread="5093.24"/>
                    <measurement group_id="B3" value="1793.3" spread="1844.72"/>
                    <measurement group_id="B4" value="981.4" spread="951.29"/>
                    <measurement group_id="B5" value="945.8" spread="962.09"/>
                    <measurement group_id="B6" value="447.8" spread="222.32"/>
                    <measurement group_id="B7" value="1726.69" spread="2740.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>IMR-687 Safety and Tolerability</title>
        <description>Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events</description>
        <time_frame>Baseline to Week 40</time_frame>
        <population>Safety Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>TDT High Dose</title>
            <description>TDT High dose</description>
          </group>
          <group group_id="O2">
            <title>TDT Low Dose</title>
            <description>TDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>TDT Placebo</title>
            <description>TDT Placebo</description>
          </group>
          <group group_id="O4">
            <title>NTDT High Dose</title>
            <description>NTDT High dose</description>
          </group>
          <group group_id="O5">
            <title>NTDT Low Dose</title>
            <description>NTDT Low dose</description>
          </group>
          <group group_id="O6">
            <title>NTDT Placebo</title>
            <description>NTDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>IMR-687 Safety and Tolerability</title>
          <description>Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events</description>
          <population>Safety Analysis set</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="29"/>
                <count group_id="O2" value="25"/>
                <count group_id="O3" value="20"/>
                <count group_id="O4" value="24"/>
                <count group_id="O5" value="12"/>
                <count group_id="O6" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treatment emergent Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="18"/>
                    <measurement group_id="O5" value="12"/>
                    <measurement group_id="O6" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment emergent Adverse Event related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="15"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="11"/>
                    <measurement group_id="O5" value="7"/>
                    <measurement group_id="O6" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 or greater treatment emergent Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="4"/>
                    <measurement group_id="O5" value="1"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24</title>
        <description>Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>TDT High Dose</title>
            <description>TDT High dose</description>
          </group>
          <group group_id="O2">
            <title>TDT Low Dose</title>
            <description>TDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>TDT Placebo</title>
            <description>TDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24</title>
          <description>Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)</description>
          <population>Per Protocol Analysis</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="21"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.</title>
        <description>Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 in the absence of transfusions.</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Per protocol analysis</population>
        <group_list>
          <group group_id="O1">
            <title>NTDT High Dose</title>
            <description>NTDT High dose</description>
          </group>
          <group group_id="O2">
            <title>NTDT Low Dose</title>
            <description>NTDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>NTDT Placebo</title>
            <description>NTDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.</title>
          <description>Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 in the absence of transfusions.</description>
          <population>Per protocol analysis</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="15"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NTDT Patients: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 12 to Week 24 in Absence of Transfusions</title>
        <description>Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>NTDT High Dose</title>
            <description>NTDT High dose</description>
          </group>
          <group group_id="O2">
            <title>NTDT Low Dose</title>
            <description>NTDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>NTDT Placebo</title>
            <description>NTDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>NTDT Patients: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 12 to Week 24 in Absence of Transfusions</title>
          <description>Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions</description>
          <population>Per Protocol Analysis</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="11"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36</title>
        <description>Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)</description>
        <time_frame>Baseline to Week 36</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>TDT High Dose</title>
            <description>TDT High dose</description>
          </group>
          <group group_id="O2">
            <title>TDT Low Dose</title>
            <description>TDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>TDT Placebo</title>
            <description>TDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36</title>
          <description>Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)</description>
          <population>Per Protocol Analysis</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="16"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.4839</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24</title>
        <description>Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)</description>
        <time_frame>Baseline to Week 24</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>TDT High Dose</title>
            <description>TDT High dose</description>
          </group>
          <group group_id="O2">
            <title>TDT Low Dose</title>
            <description>TDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>TDT Placebo</title>
            <description>TDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24</title>
          <description>Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)</description>
          <population>Per Protocol Analysis</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="21"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2065</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36</title>
        <description>Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)</description>
        <time_frame>Baseline to Week 36</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>TDT High Dose</title>
            <description>TDT High dose</description>
          </group>
          <group group_id="O2">
            <title>TDT Low Dose</title>
            <description>TDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>TDT Placebo</title>
            <description>TDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36</title>
          <description>Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)</description>
          <population>Per Protocol Analysis</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="16"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4839</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions</title>
        <description>Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 24 to Week 36 in the absence of transfusions.</description>
        <time_frame>Baseline to Week 36</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>NTDT High Dose</title>
            <description>NTDT High dose</description>
          </group>
          <group group_id="O2">
            <title>NTDT Low Dose</title>
            <description>NTDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>NTDT Placebo</title>
            <description>NTDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions</title>
          <description>Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 24 to Week 36 in the absence of transfusions.</description>
          <population>Per Protocol Analysis</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="12"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions</title>
        <description>Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions</description>
        <time_frame>Baseline to Week 36</time_frame>
        <population>Per Protocol Analysis</population>
        <group_list>
          <group group_id="O1">
            <title>NTDT High Dose</title>
            <description>NTDT High dose</description>
          </group>
          <group group_id="O2">
            <title>NTDT Low Dose</title>
            <description>NTDT Low dose</description>
          </group>
          <group group_id="O3">
            <title>NTDT Placebo</title>
            <description>NTDT Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions</title>
          <description>Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions</description>
          <population>Per Protocol Analysis</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="8"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.99</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>10 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>TDT High Dose</title>
          <description>TDT High dose</description>
        </group>
        <group group_id="E2">
          <title>TDT Low Dose</title>
          <description>TDT Low dose</description>
        </group>
        <group group_id="E3">
          <title>TDT Placebo</title>
          <description>TDT Placebo</description>
        </group>
        <group group_id="E4">
          <title>NTDT High Dose</title>
          <description>NTDT High dose</description>
        </group>
        <group group_id="E5">
          <title>NTDT Low Dose</title>
          <description>NTDT Low dose</description>
        </group>
        <group group_id="E6">
          <title>NTDT Placebo</title>
          <description>NTDT Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <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="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID19</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Liver abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lower Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Carbon Monoxide Poisoning</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Transfusion Reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lower Limb Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="25" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="18" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="12" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal Pain Upper</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomitting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>COVID19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="20"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="12"/>
              </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 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>Rahul Ballal</name_or_title>
      <organization>Imara, Inc.</organization>
      <phone>617-206-2020</phone>
      <email>rballal@imaratx.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/NCT04411082
org study id: IMR-BTL-201
secondary id: 2019-002989-12
nct id: NCT04411082
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A Study to Evaluate the Safety and Tolerability of IMR-687 in Subjects with Beta Thalassemia
A phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety,
      tolerability, PK, and PD of IMR-687 (phosphodiesterase (PDE) 9 inhibitor) administered once
      daily (qd) orally for 36 weeks in 2 populations of adult subjects with β-thalassemia:
      Population 1 (Transfusion Dependent Thalassemia (TDT) subjects) and Population 2
      (Non-Transfusion Dependent Thalassemia (NTDT) subjects).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Double-Blind
measure: IMR-687 Safety and Tolerability
time frame: Baseline to Week 40
description: Incidence and severity of Adverse Events Incidence and severity of Serious Adverse Events
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 12 to Week 24
time frame: Baseline to Week 24
description: Proportion of patients with ≥33% hematological improvement (as measured by reduced transfusion burden) from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)
measure: NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 12 to Week 24 in the Absence of Transfusions.
time frame: Baseline to Week 24
description: Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 12 to Week 24 in the absence of transfusions.
measure: NTDT Patients: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 12 to Week 24 in Absence of Transfusions
time frame: Baseline to Week 24
description: Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 12 to Week 24 in absence of transfusions
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥33% Hematological Improvement From Week 24 to Week 36
time frame: Baseline to Week 36
description: Proportion of patients with ≥33% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50 % Hematological Improvement From Week 12 to Week 24
time frame: Baseline to Week 24
description: Proportion of patients with ≥50% hematological improvement from Week 12 to Week 24 compared to the 12 weeks prior to Baseline (Day 1)
measure: TDT Patients: Reduction in Red Blood Cell (RBC) Transfusion Burden With ≥50% Hematological Improvement From Week 24 to Week 36
time frame: Baseline to Week 36
description: Proportion of patients with ≥50% hematological improvement from Week 24 to Week 36 compared to the 12 weeks prior to Baseline (Day 1)
measure: NTDT Patients: Proportion of Subjects With an Increase From Baseline of Hb at Week 24 to Week 36 in the Absence of Transfusions
time frame: Baseline to Week 36
description: Proportion of subjects with an increase from baseline of ≥1.0 g/dL in mean Hb values at Week 24 to Week 36 in the absence of transfusions.
measure: NTDT: Proportion of Subjects With an Increase From Baseline of ≥3% in Mean HbF Values at Week 24 to Week 36 in Absence of Transfusions
time frame: Baseline to Week 36
description: Proportion of subjects with an increase from baseline of ≥3% in mean HbF values at Week 24 to Week 36 in absence of transfusions
arm group label: Lower Dose IMR-687
arm group type: Experimental
description: Oral administration of once daily IMR-687
arm group label: Higher dose IMR-687
arm group type: Experimental
description: Oral administration of once daily IMR-687
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral administration of once daily placebo
intervention type: Drug
intervention name: IMR-687
description: Oral administration of once daily IMR-687
arm group label: Higher dose IMR-687
arm group label: Lower Dose IMR-687
intervention type: Drug
intervention name: Placebo
description: Oral administration of once daily Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Steve Luperchio
role: Study Director
affiliation: Cardurion Pharmaceuticals
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country: Denmark
country: France
country: Georgia
country: Greece
country: Israel
country: Italy
country: Lebanon
country: Malaysia
country: Morocco
country: Netherlands
country: Tunisia
country: Turkey
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Thalassemia
mesh term: beta-Thalassemia
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
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certain agreements: 
point of contact: 