<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/NCT03801889</url>
  </required_header>
  <id_info>
    <org_study_id>SP-420-705</org_study_id>
    <nct_id>NCT03801889</nct_id>
  </id_info>
  <brief_title>SP-420 in Subjects With Transfusion-dependent Beta-Thalassemia or Other Rare Anemias</brief_title>
  <official_title>Multicenter, Open-label, 52 Week, Dose-escalation Study of SP 420 in Subjects With Transfusion-dependent Beta-Thalassemia or Other Rare Anemias</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abfero Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abfero Pharmaceuticals, 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>
      The purpose of this study is to test the safety and tolerability of SP-420 and it's efficacy&#xD;
      in terms of lowering iron in subjects with Beta-thalassemia or other rare anemias who need&#xD;
      regular blood transfusions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Protocol suspended prior to patient enrollment&#xD;
  </why_stopped>
  <start_date type="Anticipated">August 2020</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This is a multi-center, open-label, dose-escalation study designed to evaluate the safety, tolerability, and iron clearing efficacy of SP 420 administered three-times per week in subjects with transfusion-dependent beta-thalassemia or other rare anemias. Approximately 24 subjects are to be enrolled in 3 cohorts (doses of 28 mg/kg, 56 mg/kg and 84 mg/kg) of approximately 8 subjects each. Based upon the results from lower dose cohorts, if needed the size of latter cohorts may be increased to improve the power of the study to detect efficacy to approximately 74 subjects in total.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of treatment-emergent Adverse Events (AEs)</measure>
    <time_frame>Week 24</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The incidence of treatment-emergent Adverse Events (AEs)</measure>
    <time_frame>Week 52</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in liver iron concentration (LIC) on R2-MRI from baseline</measure>
    <time_frame>Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in liver iron concentration (LIC) on R2-MRI from baseline</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiac iron content (CIC) on T2*-MRI from baseline</measure>
    <time_frame>Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiac iron content (CIC) on T2*-MRI from baseline</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total iron removed by chelator (in mg) from baseline</measure>
    <time_frame>Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total iron removed by chelator (in mg) from baseline</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Iron Overload</condition>
  <condition>Beta-Thalassemia</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SP-420 initially at 28 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SP -20 initially at 56 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SP-420 initially at 84 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SP-420</intervention_name>
    <description>Self-administered by mouth</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>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years old&#xD;
&#xD;
          -  Iron-overload secondary to β-thalassemia (homozygote or compound heterozygote) or&#xD;
             other rare anemias (e.g., aplastic anemia, pure red-cell dysplasia ) requiring chronic&#xD;
             RBC transfusions and iron chelation therapy&#xD;
&#xD;
          -  On a stable dose of iron chelation for at least 4 weeks prior to screening visit&#xD;
&#xD;
          -  Weight ≥35 kg at screening&#xD;
&#xD;
          -  Willing to discontinue current iron chelation therapy 7 days (± 3 days) prior to the&#xD;
             first dose of SP-420 and for the duration of the current study&#xD;
&#xD;
          -  LIC ≥5 and ≤25 mg/g dry weight on the R2-MRI obtained within 2 weeks prior to the&#xD;
             baseline visit&#xD;
&#xD;
          -  Cardiac T2* score &gt; 12 msec obtained on the MRI obtained within 2 weeks prior to the&#xD;
             baseline visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding&#xD;
&#xD;
          -  Current malignancy with the exceptions of localized basal cell or squamous cell skin&#xD;
             cancer or localized prostate cancer or is receiving immunotherapy, chemotherapy or&#xD;
             radiation therapy for a malignancy&#xD;
&#xD;
          -  Current myelodysplastic syndrome&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) &gt;4 times the upper limit of normal, decompensated&#xD;
             cirrhosis, or ascites at screening&#xD;
&#xD;
          -  Past history of clinically significant kidney disease (per the Principal Investigator)&#xD;
&#xD;
          -  Serum creatinine greater than the upper limit of normal during screening&#xD;
&#xD;
          -  Urine protein to creatinine ratio &gt; 0.5 mg/mg during screening&#xD;
&#xD;
          -  Ongoing symptoms of cardiac dysfunction or failure&#xD;
&#xD;
          -  Ongoing symptoms of neuropathy, including peripheral sensory neuropathy, peripheral&#xD;
             motor neuropathy, or paresthesia at screening&#xD;
&#xD;
          -  Received another investigational drug within 30 days or investigational antibody&#xD;
             within 90 days of Day 1 of the study&#xD;
&#xD;
          -  Other condition that, in the opinion of the PI, would interfere with the conduct of&#xD;
             the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ali Taher, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>American University of Beirut Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Toronto- University Health Network</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American University of Beirut Medical Center</name>
      <address>
        <city>Beirut</city>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siriraj Hospital</name>
      <address>
        <city>Bangkok</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University Hospital</name>
      <address>
        <city>İzmir</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Lebanon</country>
    <country>Thailand</country>
    <country>Turkey</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>September 30, 2020</last_update_submitted>
  <last_update_submitted_qc>September 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chelator</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>
    <mesh_term>Iron Overload</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/NCT03801889
org study id: SP-420-705
nct id: NCT03801889
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test the safety and tolerability of SP-420 and it's efficacy
      in terms of lowering iron in subjects with Beta-thalassemia or other rare anemias who need
      regular blood transfusions.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: This is a multi-center, open-label, dose-escalation study designed to evaluate the safety, tolerability, and iron clearing efficacy of SP 420 administered three-times per week in subjects with transfusion-dependent beta-thalassemia or other rare anemias. Approximately 24 subjects are to be enrolled in 3 cohorts (doses of 28 mg/kg, 56 mg/kg and 84 mg/kg) of approximately 8 subjects each. Based upon the results from lower dose cohorts, if needed the size of latter cohorts may be increased to improve the power of the study to detect efficacy to approximately 74 subjects in total.
primary purpose: Treatment
masking: None (Open Label)
measure: The incidence of treatment-emergent Adverse Events (AEs)
time frame: Week 24
measure: The incidence of treatment-emergent Adverse Events (AEs)
time frame: Week 52
measure: Change in liver iron concentration (LIC) on R2-MRI from baseline
time frame: Week 24
measure: Change in liver iron concentration (LIC) on R2-MRI from baseline
time frame: Week 52
measure: Change in cardiac iron content (CIC) on T2*-MRI from baseline
time frame: Week 24
measure: Change in cardiac iron content (CIC) on T2*-MRI from baseline
time frame: Week 52
measure: Total iron removed by chelator (in mg) from baseline
time frame: Week 24
measure: Total iron removed by chelator (in mg) from baseline
time frame: Week 52
arm group label: Cohort 1
arm group type: Experimental
description: SP-420 initially at 28 mg/kg
arm group label: Cohort 2
arm group type: Experimental
description: SP -20 initially at 56 mg/kg
arm group label: Cohort 3
arm group type: Experimental
description: SP-420 initially at 84 mg/kg
intervention type: Drug
intervention name: SP-420
description: Self-administered by mouth
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ali Taher, MD, PhD
role: Principal Investigator
affiliation: American University of Beirut Medical Center
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Lebanon
country: Thailand
country: Turkey
responsible party type: Sponsor
mesh term: Thalassemia
mesh term: beta-Thalassemia
mesh term: Iron Overload
sharing ipd: No