<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/NCT01691040</url>
  </required_header>
  <id_info>
    <org_study_id>SNOXH94C201</org_study_id>
    <secondary_id>2012-001525-27</secondary_id>
    <nct_id>NCT01691040</nct_id>
  </id_info>
  <brief_title>Efficacy of NOX-H94 on Anemia of Chronic Disease in Patients With Cancer</brief_title>
  <official_title>Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TME Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TME Pharma AG</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is conducted to determine the safety, tolerability, and efficacy of NOX-H94 in&#xD;
      patients with anemia of chronic disease (ACD). Furthermore, this study is intended to provide&#xD;
      data needed to correlate plasma concentrations of NOX-H94 with its efficacy and to choose the&#xD;
      appropriate dose and dose schedule of subsequent efficacy studies.&#xD;
&#xD;
      Some chronic diseases, e.g. tumors, inflammation, renal disease, are associated with high&#xD;
      hepcidin concentrations in the blood. These hepcidin concentrations cause a reduction in iron&#xD;
      concentrations in the blood and subsequently impair formation of red blood cells. Treatment&#xD;
      with NOX-H94 is expected to inhibit this patho-mechanism by binding and inactivating&#xD;
      hepcidin.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate of anemia</measure>
    <time_frame>treatment start to 1 week after treatment end</time_frame>
    <description>• Hb increase ≥1 g/dL OR reticulocyte index normalization (≥1%) at any time point until 1 week after the end of treatment&#xD;
AND absence of all of the following treatment failure criteria until 1 week after the end of treatment:&#xD;
Erythrocyte transfusion, ESA or IV iron,&#xD;
Hb drop by ≥1 g/dL&#xD;
Treatment interruption due to adverse events (AEs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Proportion of treatment responders at study visits V4, V6, V8, and V10 to V14, as defined for the primary efficacy endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Failure</measure>
    <time_frame>Treatment start to 1 week after end of treatment</time_frame>
    <description>Proportion of treatment failures at study visits V4, V6, V8, and V10, as defined for the primary efficacy endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Adverse events, Safety signals derived from laboratory diagnostics, vital signs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>NOX-H94 plasma concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reticulocytes</measure>
    <time_frame>Treatment start until 8 weeks after end of treatment</time_frame>
    <description>Absolute values and change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red blood cells</measure>
    <time_frame>Treatment start until 8 weeks after end of treatment</time_frame>
    <description>Absolute values and change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transferrin</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Absolute concentrations and change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum iron</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Absolute concentrations and change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ferritin</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Absolute concentrations and change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transferrin saturation</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Absolute concentrations and change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin</measure>
    <time_frame>Treatment start to 8 weeks after end of treatment</time_frame>
    <description>Absolute concentrations and change from baseline</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory analyses</measure>
    <time_frame>Treatment start to 1 week after end of treatment</time_frame>
    <description>Soluble transferrin receptor</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory analyses</measure>
    <time_frame>Treatment start to 1 week after end of treatment</time_frame>
    <description>Reticulocyte hemoglobin content</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Anemia of Chronic Disease</condition>
  <arm_group>
    <arm_group_label>Open-label pilot group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twice weekly administration of NOX-H94</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NOX-H94</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Open-label pilot group</arm_group_label>
    <other_name>lexaptepid pegol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo solution</intervention_name>
    <description>intravenous injection</description>
    <arm_group_label>Open-label pilot group</arm_group_label>
    <other_name>Glucose 5%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Female or male aged &gt;18 years&#xD;
&#xD;
          -  Clinically significant anemia of chronic disease (ACD) attributed to histologically or&#xD;
             cytologically proven malignancy, either hematological or solid tumor, of any grade or&#xD;
             stage: Hemoglobin (Hb) 7.0 g/dL to 10 g/dL, Transferrin saturation (TSAT) &lt;50%, Serum&#xD;
             iron &lt;50 µg/dL (SI: &lt;9.0 µmol/L), AND Ferritin &gt;30 ng/mL (SI: &gt;30 µg/L)&#xD;
&#xD;
          -  Previous treatment with systemic anti-cancer therapy / regimen&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2&#xD;
&#xD;
          -  Estimated life expectancy ≥12 weeks&#xD;
&#xD;
          -  Men must agree to follow effective contraception methods during treatment and for 3&#xD;
             months after completion of treatment. Women of childbearing potential must agree to&#xD;
             use two forms of effective contraception during treatment and for 3 months after&#xD;
             completion of treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to personally provide written informed consent or to understand and&#xD;
             collaborate throughout the study&#xD;
&#xD;
          -  History of pure red cell aplasia, thalassemia major or sickle cell disease History of&#xD;
             anemia unrelated to cancer &lt;10 g/dL within 6 months prior to screening&#xD;
&#xD;
          -  Uncorrected iron deficiency&#xD;
&#xD;
          -  Regular need for blood transfusions at intervals &lt;6 weeks&#xD;
&#xD;
          -  Acute or myeloid leukemia&#xD;
&#xD;
          -  Known or suspected chronic bleeding&#xD;
&#xD;
          -  Tumor with gastro-intestinal involvement without negative test for fecal occult blood&#xD;
&#xD;
          -  Suspected or known history of hemochromatosis&#xD;
&#xD;
          -  Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C&#xD;
&#xD;
          -  Impaired liver function with bilirubin ≥2.0 mg/dL (26 μmol/L), AST or ALT ≥2 times&#xD;
             upper limit&#xD;
&#xD;
          -  History or risk of significant hepatic disease, e.g. chronic alcohol abuse, hepatic&#xD;
             steatosis, hepatic cirrhosis, or organ transplantation&#xD;
&#xD;
          -  Severe renal impairment: estimated glomerular filtration rate (eGFR) &lt;30 mL/min&#xD;
             (Cockcroft-Gault)&#xD;
&#xD;
          -  Known central nervous system malignancy or metastasis&#xD;
&#xD;
          -  Significant cardiac disease (e.g. uncontrolled hypertension: systolic blood pressure&#xD;
             [BP] &gt;150 mmHg or diastolic BP &gt;100 mmHg; myocardial infarction or unstable angina&#xD;
             pectoris) within 6 months prior to screening&#xD;
&#xD;
          -  Positive pregnancy test (serum ß-hCG at screening, urine pregnancy test prior to first&#xD;
             treatment) or lactation&#xD;
&#xD;
          -  Previous participation in this study or treatment with an investigational agent &lt;21&#xD;
             days prior to treatment start&#xD;
&#xD;
          -  Hemolysis or bleeding &gt;500 mL (measured or estimated) within 6 weeks prior to&#xD;
             treatment start&#xD;
&#xD;
          -  Treatment with erythropoiesis-stimulating agents (ESAs) or red blood cell (RBC)&#xD;
             transfusions &lt;21 days prior to treatment start&#xD;
&#xD;
          -  Cytotoxic anti-tumor treatment &lt;21 days prior to treatment start or planned during the&#xD;
             anticipated study period (within 3 months from treatment start or randomization).&#xD;
             Maintenance therapy is permitted throughout the study (e.g. lenalidomide, interferon)&#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>Kai Riecke, MD</last_name>
    <role>Study Director</role>
    <affiliation>TME Pharma AG</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Graz</city>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AKH Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wilhelminenspital</name>
      <address>
        <city>Vienna</city>
        <zip>1160</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Plovdiv</city>
        <zip>4000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokuda Hospital</name>
      <address>
        <city>Sofia</city>
        <zip>1407</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Varna</city>
        <zip>9010</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Judetean</name>
      <address>
        <city>Brasov</city>
        <zip>500326</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institutul Oncologic</name>
      <address>
        <city>Cluj-Napoca</city>
        <zip>400124</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Municipal</name>
      <address>
        <city>Craiova</city>
        <zip>208028</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Judetean</name>
      <address>
        <city>Targu-Mures</city>
        <zip>540136</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncomed</name>
      <address>
        <city>Timisoara</city>
        <zip>300239</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Bulgaria</country>
    <country>Romania</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <last_update_submitted>June 25, 2014</last_update_submitted>
  <last_update_submitted_qc>June 25, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 26, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepcidin</keyword>
  <keyword>Iron</keyword>
  <keyword>Anemia of Chronic Disease</keyword>
  <keyword>Anemia</keyword>
  <keyword>Cancer</keyword>
  <keyword>Interleukin-6</keyword>
  <keyword>Iron restriction</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>CLL</keyword>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Hodgkin</keyword>
  <keyword>anti-hepcidin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Chronic Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT01691040
org study id: SNOXH94C201
secondary id: 2012-001525-27
nct id: NCT01691040
lead sponsor: 
has dmc: No
This study is conducted to determine the safety, tolerability, and efficacy of NOX-H94 in
      patients with anemia of chronic disease (ACD). Furthermore, this study is intended to provide
      data needed to correlate plasma concentrations of NOX-H94 with its efficacy and to choose the
      appropriate dose and dose schedule of subsequent efficacy studies.

      Some chronic diseases, e.g. tumors, inflammation, renal disease, are associated with high
      hepcidin concentrations in the blood. These hepcidin concentrations cause a reduction in iron
      concentrations in the blood and subsequently impair formation of red blood cells. Treatment
      with NOX-H94 is expected to inhibit this patho-mechanism by binding and inactivating
      hepcidin.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate of anemia
time frame: treatment start to 1 week after treatment end
description: • Hb increase ≥1 g/dL OR reticulocyte index normalization (≥1%) at any time point until 1 week after the end of treatment
AND absence of all of the following treatment failure criteria until 1 week after the end of treatment:
Erythrocyte transfusion, ESA or IV iron,
Hb drop by ≥1 g/dL
Treatment interruption due to adverse events (AEs)
measure: Response
time frame: Treatment start to 8 weeks after end of treatment
description: Proportion of treatment responders at study visits V4, V6, V8, and V10 to V14, as defined for the primary efficacy endpoint
measure: Failure
time frame: Treatment start to 1 week after end of treatment
description: Proportion of treatment failures at study visits V4, V6, V8, and V10, as defined for the primary efficacy endpoint
measure: Safety and tolerability
time frame: Treatment start to 8 weeks after end of treatment
description: Adverse events, Safety signals derived from laboratory diagnostics, vital signs.
measure: Pharmacokinetics
time frame: Treatment start to 8 weeks after end of treatment
description: NOX-H94 plasma concentrations
measure: Reticulocytes
time frame: Treatment start until 8 weeks after end of treatment
description: Absolute values and change from baseline
measure: Red blood cells
time frame: Treatment start until 8 weeks after end of treatment
description: Absolute values and change from baseline
measure: Transferrin
time frame: Treatment start to 8 weeks after end of treatment
description: Absolute concentrations and change from baseline
measure: Serum iron
time frame: Treatment start to 8 weeks after end of treatment
description: Absolute concentrations and change from baseline
measure: Ferritin
time frame: Treatment start to 8 weeks after end of treatment
description: Absolute concentrations and change from baseline
measure: Transferrin saturation
time frame: Treatment start to 8 weeks after end of treatment
description: Absolute concentrations and change from baseline
measure: Hemoglobin
time frame: Treatment start to 8 weeks after end of treatment
description: Absolute concentrations and change from baseline
measure: Exploratory analyses
time frame: Treatment start to 1 week after end of treatment
description: Soluble transferrin receptor
measure: Exploratory analyses
time frame: Treatment start to 1 week after end of treatment
description: Reticulocyte hemoglobin content
arm group label: Open-label pilot group
arm group type: Experimental
description: Twice weekly administration of NOX-H94
intervention type: Drug
intervention name: NOX-H94
description: intravenous injection
arm group label: Open-label pilot group
other name: lexaptepid pegol
intervention type: Drug
intervention name: Placebo solution
description: intravenous injection
arm group label: Open-label pilot group
other name: Glucose 5%
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kai Riecke, MD
role: Study Director
affiliation: TME Pharma AG
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Bulgaria
country: Romania
responsible party type: Sponsor
mesh term: Anemia
mesh term: Chronic Disease