<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/NCT04474314</url>
  </required_header>
  <id_info>
    <org_study_id>IMR-SCD-301</org_study_id>
    <secondary_id>2019-004471-39</secondary_id>
    <nct_id>NCT04474314</nct_id>
  </id_info>
  <brief_title>A Study of IMR-687 in Subjects With Sickle Cell Disease</brief_title>
  <official_title>A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease</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 Efficacy of IMR-687 in Subjects with Sickle Cell Disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A phase 2b, randomized, double-blind, placebo-controlled, multicenter study of subjects with&#xD;
      sickle cell disease (SCD; homozygous sickle hemoglobin [HbSS], sickle-β0 [HbSβ0] thalassemia,&#xD;
      or sickle-β+ [HbSβ+] thalassemia) to evaluate the safety and efficacy of the&#xD;
      phosphodiesterase type 9 (PDE9) inhibitor, IMR-687, administered once daily (qd) for 52&#xD;
      weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    A recently conducted Interim analysis of IMR-SCD-301 demonstrated that while IMR-687 was&#xD;
    generally well-tolerated, it failed to meet its primary efficacy endpoint. So, the sponsor has&#xD;
    decided to discontinue this study.&#xD;
  </why_stopped>
  <start_date type="Actual">August 13, 2020</start_date>
  <completion_date type="Actual">May 4, 2022</completion_date>
  <primary_completion_date type="Actual">March 2, 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>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Double-Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Effect on the incidence of vaso-occlusive crises (VOCs)</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>a. Annualized rate of VOCs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of patients with adverse events and serious adverse events</measure>
    <time_frame>Baseline to Week 56</time_frame>
    <description>Incidence of Adverse Events&#xD;
Incidence of Serious Adverse Events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first vaso-occlusive crises (VOCs)</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>a. Time to first VOC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of HbF response</measure>
    <time_frame>Baseline to Week 24</time_frame>
    <description>a. Proportion of Subject with response to HbF (absolute increase of ≥3%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of VOC-free subject</measure>
    <time_frame>Baseline to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized rate of hospitalizations for vaso-occlusive crises (VOCs)</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Annualized rate of hospitalizations for VOCs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to second vaso-occlusive crises (VOCs)</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Time to second VOC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of HbF response</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>a. Proportion of Subject with response to HbF (absolute increase of ≥3%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HbF and F Cells</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Change in HbF (%) and F-cells (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Subject response in total Hb</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Proportion of Subject response in total Hb (increase of ≥1.0 g/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hemolysis biomarkers</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Change in hemolysis biomarkers (% and absolute reticulocytes, unconjugated (indirect) bilirubin, and lactate dehydrogenase (LDH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on Quality of Life Measures: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®)</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on Quality of Measures: Patient-Reported Outcomes Measurements Information System (PROMIS)</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. The Patient-Reported Outcomes Measurements Information System Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on Quality of Measures: Sickle Cell Self-Efficacy Scale (SCES)</measure>
    <time_frame>Baseline to Week 24, and Week 52</time_frame>
    <description>a. Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in biomarker of adhesion</measure>
    <time_frame>Baseline to Week 24 and Week 52</time_frame>
    <description>a. Changes in biomarkers of adhesion such as soluble E-selectin, P-selectin, ICAM-1, and VCAM-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in inflammation biomarkers</measure>
    <time_frame>Baseline to Week 24 and Week 52</time_frame>
    <description>a. Changes in biomarkers of inflammation such as high-sensitivity C-reactive protein (hsCRP) and myeloperoxidase (MPO)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cardiac stress biomarkers</measure>
    <time_frame>Baseline to Week 24 and Week 52</time_frame>
    <description>a. Changes in biomarkers of cardiac stress such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect on Red Blood Cell (RBC) indices</measure>
    <time_frame>Baseline to Week 24 and Week 52</time_frame>
    <description>a. Changes in RBC indices, such as mean corpuscular volume (MCV)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">115</enrollment>
  <condition>Sickle Cell Disease</condition>
  <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>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>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. Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)&#xD;
&#xD;
          2. Hemoglobin of &gt;5.5 and &lt;10.5 g/dL; Hb values within 21 days post-transfusion will be&#xD;
             excluded.&#xD;
&#xD;
          3. Subjects must have had at least 2 and no more than 12 documented episodes of VOCs in&#xD;
             the past 12 months at the time of informed consent signing and at randomization (Day&#xD;
             1).&#xD;
&#xD;
          4. Subjects receiving HU must have received it continuously for at least 6 months prior&#xD;
             to signing informed consent, and must have been on a stable dose for at least 3 months&#xD;
             prior to signing the informed consent, with no anticipated need for dose adjustments&#xD;
             during the study including the screening period, in the opinion of the investigator.&#xD;
&#xD;
          5. Female subjects must not be pregnant or breastfeeding and be highly unlikely to become&#xD;
             pregnant. Male subjects must be unlikely to impregnate a partner.&#xD;
&#xD;
          6. 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;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4&#xD;
             days prior to randomization (Day 1).&#xD;
&#xD;
          2. Subjects participating in a chronic/prophylactic RBC transfusion program (i.e.,&#xD;
             regularly scheduled RBC transfusions); any transfusions within 21 days of screening or&#xD;
             baseline Hb measurements&#xD;
&#xD;
          3. Subjects with HbF &gt;25% at screening.&#xD;
&#xD;
          4. Significant kidney disease (eGFR &lt;45mL/min) and liver dysfunction: alanine&#xD;
             aminotransferase or aspartate aminotransferase &gt;3x upper limit of normal.&#xD;
&#xD;
          5. Body mass index (BMI) &lt;17.0 kg/m2 and a total body weight &lt;45 kg; or a BMI &gt;35 kg/m2.&#xD;
&#xD;
          6. 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;
          7. Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).&#xD;
&#xD;
          8. Prior exposure to IMR-687.&#xD;
&#xD;
          9. Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban,&#xD;
             edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least&#xD;
             28 days prior to randomization (Day 1).&#xD;
&#xD;
         10. A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months&#xD;
             prior to signing the informed consent.&#xD;
&#xD;
         11. Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth&#xD;
             factor treatment within 3 months of signing the ICF or anticipated need for such&#xD;
             agents during the study.&#xD;
&#xD;
         12. Prior gene therapy.&#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>Kenneth Attie, MD</last_name>
    <role>Study Director</role>
    <affiliation>Imara, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham School of Medicine - 1917 Clinic</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkansas Primary Care Clinic</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center For Inherited Blood Disorders</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oncology Institute Long Beach</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Connecticut Health Main Building</name>
      <address>
        <city>Farmington</city>
        <state>Connecticut</state>
        <zip>06030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Illinois at Chicago College of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612-4333</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Michigan</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newark Beth Israel Medical Center</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine - Center for Blood Disorders</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Medical Center-Temple</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University Health - Ambulatory Care Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korle Bu Teaching Hospital</name>
      <address>
        <city>Accra</city>
        <zip>PO Box 77</zip>
        <country>Ghana</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kintampo Health Research Centre</name>
      <address>
        <city>Kintampo</city>
        <zip>Brong-Ahafo Region</zip>
        <country>Ghana</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laiko General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11526</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Patras</name>
      <address>
        <city>Patra</city>
        <zip>26504</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ippokrateio General Hospital of Thessaloniki</name>
      <address>
        <city>Thessaloníki</city>
        <zip>54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero - Universitaria San Luigi Gonzaga</name>
      <address>
        <city>Turin</city>
        <state>Orbassano</state>
        <zip>10043</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli</name>
      <address>
        <city>Roma</city>
        <state>Rome</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ente Ospedaliero Ospedali Galliera</name>
      <address>
        <city>Genoa</city>
        <zip>16128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milan</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello</name>
      <address>
        <city>Palermo</city>
        <zip>90146</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kenya Medical Research Institute - Kisumu</name>
      <address>
        <city>Kisumu</city>
        <state>Nyanza</state>
        <zip>40100</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gertrude's Children's Hospital</name>
      <address>
        <city>Nairobi</city>
        <zip>00100</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Centre for Respiratory Diseases Research - Kenya Medical Research Institute</name>
      <address>
        <city>Nairobi</city>
        <zip>00100</zip>
        <country>Kenya</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Nini</name>
      <address>
        <city>Tripoli</city>
        <state>North Governorate</state>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American University of Beirut Medical Center</name>
      <address>
        <city>Beirut</city>
        <zip>01107 2020</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chronic Care Center</name>
      <address>
        <city>Hazmiyeh</city>
        <country>Lebanon</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>Hagaziekenhuis Van Den Haag - Leyweg</name>
      <address>
        <city>Den Haag</city>
        <state>South Holland</state>
        <zip>2545 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sultan Qaboos University Hospital</name>
      <address>
        <city>Muscat</city>
        <zip>123</zip>
        <country>Oman</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre National De Transfusion Sanguine - Du Senegal</name>
      <address>
        <city>Dakar</city>
        <zip>5002</zip>
        <country>Senegal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hedi Chaker Hospital</name>
      <address>
        <city>Sfax</city>
        <zip>3089</zip>
        <country>Tunisia</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>Jinja Regional Referral Hospital</name>
      <address>
        <city>Jinja</city>
        <zip>PO Box 43</zip>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uganda Cancer Institute</name>
      <address>
        <city>Kampala</city>
        <zip>PO Box 3935</zip>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Makerere University College of Health Sciences</name>
      <address>
        <city>Kampala</city>
        <zip>PO Box 7072</zip>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Joint Clinical Research Center - Lubowa</name>
      <address>
        <city>Kampala</city>
        <zip>Wskiso District</zip>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Infectious Diseases Research Collaboration - Tororo</name>
      <address>
        <city>Tororo</city>
        <zip>256</zip>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol NHS Foundation Trust</name>
      <address>
        <city>Bristol</city>
        <state>England</state>
        <zip>BS1 3NU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and Saint Thomas' NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <state>England</state>
        <zip>SE5 9RS</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>
    <facility>
      <name>Oxford University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Oxford</city>
        <state>England</state>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ghana</country>
    <country>Greece</country>
    <country>Italy</country>
    <country>Kenya</country>
    <country>Lebanon</country>
    <country>Morocco</country>
    <country>Netherlands</country>
    <country>Oman</country>
    <country>Senegal</country>
    <country>Tunisia</country>
    <country>Uganda</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>May 9, 2022</last_update_submitted>
  <last_update_submitted_qc>May 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sickle Cell Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>June 8, 2022</submitted>
    <returned>July 1, 2022</returned>
    <submitted>July 5, 2022</submitted>
    <returned>July 21, 2022</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04474314
org study id: IMR-SCD-301
secondary id: 2019-004471-39
nct id: NCT04474314
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease
A phase 2b, randomized, double-blind, placebo-controlled, multicenter study of subjects with
      sickle cell disease (SCD; homozygous sickle hemoglobin [HbSS], sickle-β0 [HbSβ0] thalassemia,
      or sickle-β+ [HbSβ+] thalassemia) to evaluate the safety and efficacy of the
      phosphodiesterase type 9 (PDE9) inhibitor, IMR-687, administered once daily (qd) for 52
      weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Double-Blind
measure: Effect on the incidence of vaso-occlusive crises (VOCs)
time frame: Baseline to Week 52
description: a. Annualized rate of VOCs
measure: Proportion of patients with adverse events and serious adverse events
time frame: Baseline to Week 56
description: Incidence of Adverse Events
Incidence of Serious Adverse Events
measure: Time to first vaso-occlusive crises (VOCs)
time frame: Baseline to Week 52
description: a. Time to first VOC
measure: Proportion of HbF response
time frame: Baseline to Week 24
description: a. Proportion of Subject with response to HbF (absolute increase of ≥3%)
measure: Proportion of VOC-free subject
time frame: Baseline to Week 52
measure: Annualized rate of hospitalizations for vaso-occlusive crises (VOCs)
time frame: Baseline to Week 24, and Week 52
description: a. Annualized rate of hospitalizations for VOCs
measure: Time to second vaso-occlusive crises (VOCs)
time frame: Baseline to Week 24, and Week 52
description: a. Time to second VOC
measure: Proportion of HbF response
time frame: Baseline to Week 52
description: a. Proportion of Subject with response to HbF (absolute increase of ≥3%)
measure: Change in HbF and F Cells
time frame: Baseline to Week 24, and Week 52
description: a. Change in HbF (%) and F-cells (%)
measure: Proportion of Subject response in total Hb
time frame: Baseline to Week 24, and Week 52
description: a. Proportion of Subject response in total Hb (increase of ≥1.0 g/dL)
measure: Change in hemolysis biomarkers
time frame: Baseline to Week 24, and Week 52
description: a. Change in hemolysis biomarkers (% and absolute reticulocytes, unconjugated (indirect) bilirubin, and lactate dehydrogenase (LDH)
measure: Effect on Quality of Life Measures: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®)
time frame: Baseline to Week 24, and Week 52
description: a. Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®).
measure: Effect on Quality of Measures: Patient-Reported Outcomes Measurements Information System (PROMIS)
time frame: Baseline to Week 24, and Week 52
description: a. The Patient-Reported Outcomes Measurements Information System Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr]).
measure: Effect on Quality of Measures: Sickle Cell Self-Efficacy Scale (SCES)
time frame: Baseline to Week 24, and Week 52
description: a. Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES).
measure: Changes in biomarker of adhesion
time frame: Baseline to Week 24 and Week 52
description: a. Changes in biomarkers of adhesion such as soluble E-selectin, P-selectin, ICAM-1, and VCAM-1
measure: Changes in inflammation biomarkers
time frame: Baseline to Week 24 and Week 52
description: a. Changes in biomarkers of inflammation such as high-sensitivity C-reactive protein (hsCRP) and myeloperoxidase (MPO)
measure: Changes in cardiac stress biomarkers
time frame: Baseline to Week 24 and Week 52
description: a. Changes in biomarkers of cardiac stress such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)
measure: Effect on Red Blood Cell (RBC) indices
time frame: Baseline to Week 24 and Week 52
description: a. Changes in RBC indices, such as mean corpuscular volume (MCV)
arm group label: Higher dose IMR-687
arm group type: Experimental
description: Oral administration of once daily IMR-687
arm group label: Lower 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: Kenneth Attie, MD
role: Study Director
affiliation: Imara, Inc.
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country: Ghana
country: Greece
country: Italy
country: Kenya
country: Lebanon
country: Morocco
country: Netherlands
country: Oman
country: Senegal
country: Tunisia
country: Uganda
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
submitted: June 8, 2022
returned: July 1, 2022
submitted: July 5, 2022
returned: July 21, 2022