<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/NCT02998450</url>
  </required_header>
  <id_info>
    <org_study_id>IMR-SCD-101</org_study_id>
    <nct_id>NCT02998450</nct_id>
  </id_info>
  <brief_title>A Study of IMR-687 in Healthy Adult Volunteers</brief_title>
  <official_title>A Phase 1a Study of IMR-687 in Healthy Adult Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imara, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quintiles, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Imara, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this Phase 1a, first in human, randomized, double-blind, placebo-controlled&#xD;
      study is to evaluate the safety, tolerability, PK and PD profile of the orally administered&#xD;
      IMR-687 in healthy adult subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 18, 2016</start_date>
  <completion_date type="Actual">July 8, 2017</completion_date>
  <primary_completion_date type="Actual">July 8, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment emergent adverse events and serious adverse events</measure>
    <time_frame>5 Days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes from baseline in vital signs</measure>
    <time_frame>Baseline to Day 5</time_frame>
    <description>Vital signs include blood pressure, heart rate, pulse rate, and oral temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes from baseline in physical examination</measure>
    <time_frame>Baseline to Day 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes from baseline in hematology, chemistry, coagulation and urinalysis laboratory values</measure>
    <time_frame>Baseline to Day 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes from baseline in 12-lead ECG parameters</measure>
    <time_frame>Baseline to Day 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Use of concomitant medications and therapies, medication type and frequency</measure>
    <time_frame>5 Days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of IMR-687</measure>
    <time_frame>Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose</time_frame>
    <description>Maximum Observed Plasma Concentration (Cmax) of IMR-687</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of IMR-687</measure>
    <time_frame>Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose</time_frame>
    <description>Area under the curve (AUC) ( 0 to 24 h) of IMR-687</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of IMR-687</measure>
    <time_frame>Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose</time_frame>
    <description>AUC from time 0 to the last measurable time point (AUClast) of IMR-687</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of IMR-687</measure>
    <time_frame>Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose</time_frame>
    <description>AUC extrapolated to infinity (AUC0 ∞) of IMR-687</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of IMR-687</measure>
    <time_frame>Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose</time_frame>
    <description>Time to maximum concentration (tmax) of IMR-687</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of IMR-687</measure>
    <time_frame>Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose</time_frame>
    <description>Apparent terminal half-life (t½) of IMR-687</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change from baseline in QTcF interval.</measure>
    <time_frame>2 Days</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Sickle Cell Disease</condition>
  <condition>Sickle-Cell; Hb-SC</condition>
  <condition>Sickle Beta 0 Thalassemia</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive a single low dose of IMR-687, administered orally following an overnight fast.&#xD;
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive a single low-mid dose of IMR-687, administered orally following an overnight fast.&#xD;
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive a single mid-low dose of IMR-687, administered orally following an overnight fast.&#xD;
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive a single mid dose of IMR-687, administered orally following an overnight fast.&#xD;
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive a single mid-high dose of IMR-687, administered orally following an overnight fast.&#xD;
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 Subjects will receive a single high dose of IMR-687, administered orally following an overnight fast.&#xD;
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMR-687</intervention_name>
    <description>1 of 6 possible single doses administered orally following overnight fast</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_label>Cohort 6</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Capsule</intervention_name>
    <description>Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_label>Cohort 5</arm_group_label>
    <arm_group_label>Cohort 6</arm_group_label>
    <other_name>Microcrystalline cellulose</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be healthy as judged by the Investigator on the basis of pre-study tests performed at&#xD;
             Screening, with healthy body mass index (BMI), healthy body weight, and laboratory&#xD;
             results within normal laboratory reference range or determined not to be clinically&#xD;
             significant by the Investigator; and be free from drugs of abuse.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females who are pregnant, trying to become pregnant, or breastfeeding; and males with&#xD;
             female partners who are trying to conceive.&#xD;
&#xD;
          -  Asthmatics or other individuals who use or may use albuterol rescue inhalers or&#xD;
             nebulizers.&#xD;
&#xD;
          -  A significant history of cardiovascular disease.&#xD;
&#xD;
          -  On ECG, a QTcF &gt;450 ms or the presence of clinically significant abnormalities as&#xD;
             determined by the Investigator.&#xD;
&#xD;
          -  Elevated blood pressure.&#xD;
&#xD;
          -  Use within 30 days prior to Day 1 of any inhibitors or substrates of targets of&#xD;
             IMR-687.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Regulatory Operations</last_name>
    <role>Study Director</role>
    <affiliation>Cardurion Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quintiles</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_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>Sickle Cell Disease</keyword>
  <keyword>Sickle Beta 0 Thalassemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>Hemoglobin SC Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02998450
org study id: IMR-SCD-101
nct id: NCT02998450
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this Phase 1a, first in human, randomized, double-blind, placebo-controlled
      study is to evaluate the safety, tolerability, PK and PD profile of the orally administered
      IMR-687 in healthy adult subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants with treatment emergent adverse events and serious adverse events
time frame: 5 Days
measure: Number of participants with clinically significant changes from baseline in vital signs
time frame: Baseline to Day 5
description: Vital signs include blood pressure, heart rate, pulse rate, and oral temperature
measure: Number of participants with clinically significant changes from baseline in physical examination
time frame: Baseline to Day 5
measure: Number of participants with clinically significant changes from baseline in hematology, chemistry, coagulation and urinalysis laboratory values
time frame: Baseline to Day 5
measure: Number of participants with clinically significant changes from baseline in 12-lead ECG parameters
time frame: Baseline to Day 2
measure: Use of concomitant medications and therapies, medication type and frequency
time frame: 5 Days
measure: Pharmacokinetics (PK) of IMR-687
time frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose
description: Maximum Observed Plasma Concentration (Cmax) of IMR-687
measure: Pharmacokinetics (PK) of IMR-687
time frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose
description: Area under the curve (AUC) ( 0 to 24 h) of IMR-687
measure: Pharmacokinetics (PK) of IMR-687
time frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose
description: AUC from time 0 to the last measurable time point (AUClast) of IMR-687
measure: Pharmacokinetics (PK) of IMR-687
time frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose
description: AUC extrapolated to infinity (AUC0 ∞) of IMR-687
measure: Pharmacokinetics (PK) of IMR-687
time frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose
description: Time to maximum concentration (tmax) of IMR-687
measure: Pharmacokinetics (PK) of IMR-687
time frame: Day 1 prior to administration of drug and 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post dose
description: Apparent terminal half-life (t½) of IMR-687
measure: The change from baseline in QTcF interval.
time frame: 2 Days
arm group label: Cohort 1
arm group type: Experimental
description: 4 Subjects will receive a single low dose of IMR-687, administered orally following an overnight fast.
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.
arm group label: Cohort 2
arm group type: Experimental
description: 4 Subjects will receive a single low-mid dose of IMR-687, administered orally following an overnight fast.
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.
arm group label: Cohort 3
arm group type: Experimental
description: 4 Subjects will receive a single mid-low dose of IMR-687, administered orally following an overnight fast.
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.
arm group label: Cohort 4
arm group type: Experimental
description: 4 Subjects will receive a single mid dose of IMR-687, administered orally following an overnight fast.
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.
arm group label: Cohort 5
arm group type: Experimental
description: 4 Subjects will receive a single mid-high dose of IMR-687, administered orally following an overnight fast.
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.
arm group label: Cohort 6
arm group type: Experimental
description: 4 Subjects will receive a single high dose of IMR-687, administered orally following an overnight fast.
2 Subjects will receive a single dose of Placebo, administered orally following an overnight fast.
intervention type: Drug
intervention name: IMR-687
description: 1 of 6 possible single doses administered orally following overnight fast
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
arm group label: Cohort 5
arm group label: Cohort 6
intervention type: Drug
intervention name: Placebo Oral Capsule
description: Placebo oral capsule with 50 mg microcrystalline cellulose in capsules identical to those used for the active pharmaceutical ingredient.
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
arm group label: Cohort 5
arm group label: Cohort 6
other name: Microcrystalline cellulose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Regulatory Operations
role: Study Director
affiliation: Cardurion Pharmaceuticals
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anemia, Sickle Cell
mesh term: Thalassemia
mesh term: Hemoglobin SC Disease
sharing ipd: No