<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/NCT01695759</url>
  </required_header>
  <id_info>
    <org_study_id>EPOBLA1011</org_study_id>
    <secondary_id>Emenda 04 - 11/May/2015</secondary_id>
    <nct_id>NCT01695759</nct_id>
  </id_info>
  <brief_title>Clinical Efficacy of Two Erythropoietin Drug in Participants With Secondary Anemia to Chronic Kidney Disease.</brief_title>
  <official_title>Evaluation of Clinical Efficacy and Immunogenicity of Drug Eritromax® at Blau Farmacêutica S.A. Compared to Eprex®, Produced by Janssen-Cilag Laboratory in Participants With Secondary Anemia to Chronic Kidney Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azidus Brasil</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Blau Farmaceutica S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Azidus Brasil</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, randomized, multicenter, parallel, placebo-controlled, phase III study&#xD;
      for evaluation of clinical efficacy and immunogenicity of drug Eritromax® - (rHuEPO Blau&#xD;
      Farmacêutica S/A.) compared to Eprex® (Janssen-Cilag rHuEPO) for the treatment of patients&#xD;
      with secondary anemia to chronic kidney disease (CKD), throughout the correction phase by&#xD;
      assessing the change in hemoglobin levels.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase III study, in which participants with secondary anemia to chronic kidney&#xD;
      disease will receive two subcutaneous injection of 50 UI/Kg of the investigational product&#xD;
      (Eritromax®) or Eprex® per week. After four weeks of treatment, the dose of drugs will be&#xD;
      change by clinical judged throughout study according to laboratory results. The evidence of&#xD;
      efficacy will be evaluated by hemoglobin levels alteration throughout the correction phase&#xD;
      (first four weeks). Secondary efficacy and safety endpoints will be assessed by: maintenance&#xD;
      of hemoglobin levels (baseline vs. end of treatment) over maintenance phase; dose of EPO&#xD;
      required during correction and maintenance phase; Transfusion needs; report of adverse events&#xD;
      (including type, frequency, intensity, serioussness, severity and relation to the&#xD;
      investigation product) throughouht 12 months of follow-up. Additionally, the immunological&#xD;
      response of products over study will be evaluated by quantification of anti-erythropoietin&#xD;
      every six months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">December 2013</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 3</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of hemoglobin levels at correction phase (baseline vs end of treatment)</measure>
    <time_frame>until 6 months</time_frame>
    <description>In the correction phase, change in serum Hb levels (baseline vs. end of initial treatment (EOIT) = levels of Hb presented before the V0 treatment compared to the Hb levels presented at the end of the correction phase) will be evaluated for a maximum period of 6 months after starting treatment. This one parameter will be demonstrated through: Percentage of participants achieving Hb levels within the target (≥ 10.5 to ≤ 12 g / dL).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maintenance of hemoglobin levels</measure>
    <time_frame>until the end of 12 months</time_frame>
    <description>Will be evaluated by porcentage of participants whose Hb levels remained within the therapeutic range (≥10,5 a ≤ 12 g/dL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adjustment of EPO dose required during correction and/or maintenance phase</measure>
    <time_frame>until the end of 12 months</time_frame>
    <description>Will be evaluated by mean dose of EPO used between groups and number of participants that needed of dose adjustment over correction and/or maintenance phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transfusion needs</measure>
    <time_frame>until the end of 12 months</time_frame>
    <description>Will be evaluated by porcentage of participants that needed of blood transfusion throughout the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Report of Adverse Events</measure>
    <time_frame>until the end of 12 months</time_frame>
    <description>Will be evaluated by report of adverse events throughout the study. The Adverse events will be classified about the type, frequency, intensity, seriousness, severity and relation to the investigational product.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Immunological Response</measure>
    <time_frame>every six months</time_frame>
    <description>The immunological response induced by epoetin alpha will be evaluated by quantification of anti-erithropoetin antibodies, every six months.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">92</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>Epoetin alpha</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eritromax), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Eprex</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eprex), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epoetin alpha</intervention_name>
    <description>Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eritromax), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.</description>
    <arm_group_label>Epoetin alpha</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eprex</intervention_name>
    <description>Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eprex), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.</description>
    <arm_group_label>Eprex</arm_group_label>
    <other_name>Epoetin alpha</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Voluntary participation and agree to all the purposes of the study by signing and&#xD;
             dating ICF;&#xD;
&#xD;
          2. Male or female participantes, regardless of race or social class;&#xD;
&#xD;
          3. Participants aged ≥18 and ≤70 years;&#xD;
&#xD;
          4. Bearer dialysis-dependent CKD (hemodialysis and peritoneal dialysis *);&#xD;
&#xD;
          5. Clinical diagnosis of anemia, characterized as hemoglobin levels &lt;10g/dL before the&#xD;
             start of the study;&#xD;
&#xD;
          6. Adequate dialysis: Kt / V ≥ 1.2 for hemodialysis patients (based on the calculation of&#xD;
             Daugirdas II) and ≥ 1.7 for patients on peritoneal dialysis;&#xD;
&#xD;
          7. Adequate iron stores (TSAT&gt; 20% and serum ferritin&gt; 100ng/ml) prior to initiation of&#xD;
             treatment with erythropoietin.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation in clinical trials in the 12 months preceding the survey;&#xD;
&#xD;
          2. Patients with uncontrolled hypertension, with mean above 180/100mmHg and whose&#xD;
             requiring hospitalization in the last 6 months;&#xD;
&#xD;
          3. Presence of other causes of anemia than CKD, such as bleeding, hemolysis, pernicious&#xD;
             anemia and hemoglobinopathies;&#xD;
&#xD;
          4. Patients who present changes or clinical abnormalities, qualified as interfering&#xD;
             changes, such as severe hyperparathyroidism (iPTH&gt; 1000 pg / mL), severe congestive&#xD;
             heart failure (NYHA Class IV), acute myocardial infarction within the last 3 months,&#xD;
             or active neoplasia in follow-up, severe liver disease, active infection (leukocyte&#xD;
             changes), history of aluminum toxicity or scheduled surgery, pregnancy or lactation;&#xD;
&#xD;
          5. Patients who have a known hypersensitivity to any component of the formulation and to&#xD;
             products derived from mammalian cells;&#xD;
&#xD;
          6. Prior therapies with erythropoietin for less than 3 months;&#xD;
&#xD;
          7. Realization transfusion for less than 3 months;&#xD;
&#xD;
          8. Any situation at the discretion of the Principal Investigator interfere with study&#xD;
             data.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Regiane Braga, Analyst</last_name>
    <role>Study Chair</role>
    <affiliation>Blau Farmaceutica S.A.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clínica Senhor do Bomfim Ltda</name>
      <address>
        <city>Feira de Santana</city>
        <state>Bahia</state>
        <zip>44001-584</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Scribner de Ensino, Pesquisa, Ciência e Tecnologia</name>
      <address>
        <city>Curitiba</city>
        <state>Parana</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundação Universitária de Caxias do Sul - Instituto de Pesquisa Clínica para Estudos Multicêntricos</name>
      <address>
        <city>Caxias do Sul</city>
        <state>Rio Grande Do Sul</state>
        <zip>95070-561</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irmandade da Santa Casa de Misericórdia de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>União Brasileira de Educação e Assistência Hospital São Lucas da PUCRS</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundação Pró-Rim</name>
      <address>
        <city>Joinville</city>
        <state>Santa Catarina</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Ensino Padre Anchieta</name>
      <address>
        <city>São Bernardo do Campo</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CMIN - Clínica De Medicina Interna E Nefrologia</name>
      <address>
        <city>São Paulo</city>
        <zip>05001-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundação Oswaldo Cruz (Hospital do Rim e Hipertensão)</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Real e Benemérita Associação Portuguesa de Beneficência São Paulo (Hospital Beneficência Portuguesa)</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <last_update_submitted>August 17, 2018</last_update_submitted>
  <last_update_submitted_qc>August 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anemia Secondary</keyword>
  <keyword>Chronic Kidney Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Anemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epoetin Alfa</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT01695759
org study id: EPOBLA1011
secondary id: Emenda 04 - 11/May/2015
nct id: NCT01695759
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, randomized, multicenter, parallel, placebo-controlled, phase III study
      for evaluation of clinical efficacy and immunogenicity of drug Eritromax® - (rHuEPO Blau
      Farmacêutica S/A.) compared to Eprex® (Janssen-Cilag rHuEPO) for the treatment of patients
      with secondary anemia to chronic kidney disease (CKD), throughout the correction phase by
      assessing the change in hemoglobin levels.
This is a phase III study, in which participants with secondary anemia to chronic kidney
      disease will receive two subcutaneous injection of 50 UI/Kg of the investigational product
      (Eritromax®) or Eprex® per week. After four weeks of treatment, the dose of drugs will be
      change by clinical judged throughout study according to laboratory results. The evidence of
      efficacy will be evaluated by hemoglobin levels alteration throughout the correction phase
      (first four weeks). Secondary efficacy and safety endpoints will be assessed by: maintenance
      of hemoglobin levels (baseline vs. end of treatment) over maintenance phase; dose of EPO
      required during correction and maintenance phase; Transfusion needs; report of adverse events
      (including type, frequency, intensity, serioussness, severity and relation to the
      investigation product) throughouht 12 months of follow-up. Additionally, the immunological
      response of products over study will be evaluated by quantification of anti-erythropoietin
      every six months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Change of hemoglobin levels at correction phase (baseline vs end of treatment)
time frame: until 6 months
description: In the correction phase, change in serum Hb levels (baseline vs. end of initial treatment (EOIT) = levels of Hb presented before the V0 treatment compared to the Hb levels presented at the end of the correction phase) will be evaluated for a maximum period of 6 months after starting treatment. This one parameter will be demonstrated through: Percentage of participants achieving Hb levels within the target (≥ 10.5 to ≤ 12 g / dL).
measure: Maintenance of hemoglobin levels
time frame: until the end of 12 months
description: Will be evaluated by porcentage of participants whose Hb levels remained within the therapeutic range (≥10,5 a ≤ 12 g/dL).
measure: Adjustment of EPO dose required during correction and/or maintenance phase
time frame: until the end of 12 months
description: Will be evaluated by mean dose of EPO used between groups and number of participants that needed of dose adjustment over correction and/or maintenance phase.
measure: Transfusion needs
time frame: until the end of 12 months
description: Will be evaluated by porcentage of participants that needed of blood transfusion throughout the study.
measure: Report of Adverse Events
time frame: until the end of 12 months
description: Will be evaluated by report of adverse events throughout the study. The Adverse events will be classified about the type, frequency, intensity, seriousness, severity and relation to the investigational product.
measure: Immunological Response
time frame: every six months
description: The immunological response induced by epoetin alpha will be evaluated by quantification of anti-erithropoetin antibodies, every six months.
arm group label: Epoetin alpha
arm group type: Experimental
description: Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eritromax), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.
arm group label: Eprex
arm group type: Active Comparator
description: Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eprex), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.
intervention type: Drug
intervention name: Epoetin alpha
description: Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eritromax), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.
arm group label: Epoetin alpha
intervention type: Drug
intervention name: Eprex
description: Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eprex), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.
arm group label: Eprex
other name: Epoetin alpha
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Regiane Braga, Analyst
role: Study Chair
affiliation: Blau Farmaceutica S.A.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Anemia
mesh term: Epoetin Alfa
sharing ipd: Undecided