<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/NCT04468100</url>
  </required_header>
  <id_info>
    <org_study_id>DRN-CFR-III</org_study_id>
    <secondary_id>348 eff date 23.06.2017</secondary_id>
    <nct_id>NCT04468100</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Tigerase® vs. Pulmozyme® in Patients With Cystic Fibrosis</brief_title>
  <official_title>A Multicenter Prospective Randomized Comparative Study of Pharmacokinetics, Clinical Efficacy and Safety of Tigerase® (JSC GENERIUM, Russia) vs. Pulmozyme® (Hoffmann-La Roche, Switzerland) as Part of Complex Therapy in Patients With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AO GENERIUM</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AO GENERIUM</source>
  <oversight_info>
    <has_dmc>No</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>
      It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety&#xD;
      of Tigerase® compared Pulmozyme® in patients with Cystic Fibrosis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cystic fibrosis (CF) is a common hereditary disease with an autosomal recessive type of&#xD;
      inheritance, characterized by systemic damage to the exocrine glands, mainly the&#xD;
      bronchopulmonary and gastrointestinal systems. CF is usually characterized by a severe course&#xD;
      and poor prognosis. The severity of the disease and the life expectancy of the patient with&#xD;
      CF is determined primarily by the state of the bronchopulmonary system; more than 90% of&#xD;
      patients die from lung diseases.&#xD;
&#xD;
      CF Pulmonary damage develops as a result of a gene mutation - cystic fibrosis transmembrane&#xD;
      regulator of ion conductivity Na and Cl (CFTR-cystic fibrosis transmembrane regulator). The&#xD;
      main function of CFTR is to regulate the transport of sodium and chlorine across the cell&#xD;
      membrane and is part of the cAMP-dependent chlorine channel. CFTR-protein dysfunction in the&#xD;
      bronchial tree epithelial cells leads to a blockage of the chlorine ions transport and an&#xD;
      increase in the sodium ions absorption, and impaired fluid secretion through the epithelial&#xD;
      cells apical membrane.&#xD;
&#xD;
      Dornase alpha, a human recombinant deoxyribonuclease 1 (rhDNase, rhDNase) hydrolyzes&#xD;
      extracellular DNA (viscous polyanion) that enters the sputum from destroyed neutrophils,&#xD;
      thereby reducing the adhesion and viscosity of sputum. In CF patients dornase alpha is used&#xD;
      as symptomatic therapy in combination with standard therapy in patients with a forced vital&#xD;
      capacity (FVC) index of at least 40% of the proper value.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 30, 2017</start_date>
  <completion_date type="Actual">May 16, 2018</completion_date>
  <primary_completion_date type="Actual">May 16, 2018</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline</measure>
    <time_frame>FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry</time_frame>
    <description>Week 24 ± 1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in forced lung capacity (FVC) compared to baseline</measure>
    <time_frame>Week 24 ± 1</time_frame>
    <description>FVC - forced lung capacity by standard spirometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of exacerbations of chronic pulmonary disease</measure>
    <time_frame>Week 24 ± 1</time_frame>
    <description>Clinical symptoms of chronic pulmonary disease exacerbation required antibiotic therapy in CF patients, include the presence of at least 4 of 12 possible signs or symptoms&#xD;
A change in color or amount of sputum;&#xD;
The appearance or intensification of hemoptysis;&#xD;
Strengthening cough;&#xD;
Increased shortness of breath;&#xD;
Increased malaise, fatigue or lethargy;&#xD;
Temperature above 38 ° C;&#xD;
Anorexia or weight loss;&#xD;
Sinuses pain or soreness;&#xD;
Changes in the nature of sinuses mucus;&#xD;
Changes in chest physical examination;&#xD;
Pulmonary function decrease at list 10% or more;&#xD;
Radiographic changes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of days before the chronic pulmonary disease exacerbation development</measure>
    <time_frame>Week 24 ± 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body weight compared to baseline</measure>
    <time_frame>Week 24 ± 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the average score for the &quot;Symptoms&quot;, &quot;Activity&quot;, &quot;Influence&quot; subscales, as well as the average total score of the St. George's Respiratory Questionnaire (SGRQ), version 2.2</measure>
    <time_frame>Week 24 ± 1</time_frame>
    <description>St. George's Respiratory Questionnaire (SGRQ), a questionnaire for patients with respiratory diseases is designed to assess the chronic obstructive pulmonary disease patients quality of life.&#xD;
The questionnaire consists of 76 questions, which are grouped in 3 parts:&#xD;
The first part - symptoms - measures the degree of anxiety caused by respiratory symptoms.&#xD;
The second part - activity - measures the limitation of mobility and physical activity.&#xD;
The third part - the influence - evaluates the existing psychosocial consequences of bronchial obstruction.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Cystic Fibrosis</condition>
  <condition>Fibrosis</condition>
  <arm_group>
    <arm_group_label>Tigerase®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dornase alfa</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pulmozyme®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dornase alfa</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tigerase®</intervention_name>
    <description>2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days</description>
    <arm_group_label>Tigerase®</arm_group_label>
    <other_name>dornase alfa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pulmozyme®</intervention_name>
    <description>2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days</description>
    <arm_group_label>Pulmozyme®</arm_group_label>
    <other_name>dornase alfa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Patient Informed Consent Form for participation in the study;&#xD;
&#xD;
          2. Men and women 18 years and older;&#xD;
&#xD;
          3. Diagnosis of cystic fibrosis, defined as the presence of disease symptoms and a&#xD;
             positive sweat test and / or detection of 2 mutations of the MVTR gene during&#xD;
             genotyping;&#xD;
&#xD;
          4. FEV1 ≥40% and ≤100% of the proper value;&#xD;
&#xD;
          5. The ability to understand the protocol requirements, to give written consent to&#xD;
             participate in the study (including the use and transfer of information about the&#xD;
             patient's health status related to the study).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity to any of used study drug, to their components, as well as a history&#xD;
             of significant allergic reactions;&#xD;
&#xD;
          2. Acute respiratory infection or exacerbation of chronic pulmonary disease within 4&#xD;
             weeks prior to screening and without corticosteroid or antibiotic therapy;&#xD;
&#xD;
          3. Concomitant diseases and conditions with potential impact the patients safety,&#xD;
             including:&#xD;
&#xD;
               -  Severe renal impairment (serum creatinine more than 1.5 times higher than the&#xD;
                  upper limit of normal);&#xD;
&#xD;
               -  Severe liver impairment (alanine aminotransferase (ALT) or aspartate&#xD;
                  aminotransferase (AST) blood serum activity is 2.5 times or more higher than the&#xD;
                  upper limit of the laboratory norm);&#xD;
&#xD;
          4. A history of lung transplantation or planned transplantation during this study;&#xD;
&#xD;
          5. The presence of antibodies to HIV, active viral hepatitis B and / or C and / or&#xD;
             cirrhosis in the history or detected on Screening;&#xD;
&#xD;
          6. Pregnancy and lactation;&#xD;
&#xD;
          7. Refusal of patients with preserved reproductive potential to use adequate&#xD;
             contraception throughout the study and within 30 days after the end of the study;&#xD;
&#xD;
          8. Patients who underwent a blood or blood components transfusion within 10 days prior to&#xD;
             screening;&#xD;
&#xD;
          9. Drug or alcohol abuse at the time of Screening or in the past;&#xD;
&#xD;
         10. Patient's participation in any other clinical trials and / or administration of an&#xD;
             experimental drug within 30 days prior to the Screening Visit.&#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>Oksana A. Markova, MD</last_name>
    <role>Study Chair</role>
    <affiliation>AO GENERIUM</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Regional Clinical Hospital</name>
      <address>
        <city>Barnaul</city>
        <state>Altai Region</state>
        <zip>656024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Crimean federal university named after V.I.Vernadsky</name>
      <address>
        <city>Simferopol</city>
        <state>Crimea Republic</state>
        <zip>295007</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical hospital named after G.G. Kuvatov</name>
      <address>
        <city>Ufa</city>
        <state>Republic Of Bashkortostan</state>
        <zip>450005</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kazan state medical University of Ministry of health, Hospital Therapy Department</name>
      <address>
        <city>Kazan</city>
        <state>Republic Of Tatarstan</state>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sverdlovsk Regional clinical hospital No. 1</name>
      <address>
        <city>Ekaterinburg</city>
        <state>Sverdlovsk Region</state>
        <zip>620102</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chelyabinsk Regional Clinical hospital</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454076</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Hospital named after D.D. Pletnev</name>
      <address>
        <city>Moscow</city>
        <zip>105077</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Multidisciplinary Hospital No. 2</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>194354</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional clinical Hospital</name>
      <address>
        <city>Saratov</city>
        <zip>410053</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientific medical center of General Medicine and pharmacologies</name>
      <address>
        <city>Stavropol</city>
        <zip>355000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tomsk national medical research Center of the Russian Academy of Sciences, Genetic Clinic Research Institute medical genetics</name>
      <address>
        <city>Tomsk</city>
        <zip>634050</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Volgograd State Medical University, Department of clinical pharmacology and intensive care</name>
      <address>
        <city>Volgograd</city>
        <zip>400066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Clinical Hospital No. 1 &quot;, Cystic Fibrosis center</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical hospital No. 2</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150010</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dornase</keyword>
  <keyword>Cystic Fibrosis</keyword>
  <keyword>Fibrosis</keyword>
  <keyword>Lung Diseases</keyword>
  <keyword>Pancreatic Diseases</keyword>
  <keyword>Digestive System Diseases</keyword>
  <keyword>Respiratory Tract Diseases</keyword>
  <keyword>Pathologic Processes</keyword>
  <keyword>Genetic Diseases, Inborn</keyword>
  <keyword>Tigerase®</keyword>
  <keyword>DNase</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</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/NCT04468100
org study id: DRN-CFR-III
secondary id: 348 eff date 23.06.2017
nct id: NCT04468100
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is a multicenter, open-label, randomized, parallel-group study of the efficacy and safety
      of Tigerase® compared Pulmozyme® in patients with Cystic Fibrosis
Cystic fibrosis (CF) is a common hereditary disease with an autosomal recessive type of
      inheritance, characterized by systemic damage to the exocrine glands, mainly the
      bronchopulmonary and gastrointestinal systems. CF is usually characterized by a severe course
      and poor prognosis. The severity of the disease and the life expectancy of the patient with
      CF is determined primarily by the state of the bronchopulmonary system; more than 90% of
      patients die from lung diseases.

      CF Pulmonary damage develops as a result of a gene mutation - cystic fibrosis transmembrane
      regulator of ion conductivity Na and Cl (CFTR-cystic fibrosis transmembrane regulator). The
      main function of CFTR is to regulate the transport of sodium and chlorine across the cell
      membrane and is part of the cAMP-dependent chlorine channel. CFTR-protein dysfunction in the
      bronchial tree epithelial cells leads to a blockage of the chlorine ions transport and an
      increase in the sodium ions absorption, and impaired fluid secretion through the epithelial
      cells apical membrane.

      Dornase alpha, a human recombinant deoxyribonuclease 1 (rhDNase, rhDNase) hydrolyzes
      extracellular DNA (viscous polyanion) that enters the sputum from destroyed neutrophils,
      thereby reducing the adhesion and viscosity of sputum. In CF patients dornase alpha is used
      as symptomatic therapy in combination with standard therapy in patients with a forced vital
      capacity (FVC) index of at least 40% of the proper value.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in forced expiratory volume in the first second of a forced expiratory maneuver (FEV1) compared to baseline
time frame: FEV1 - forced expiratory volume in the first second of a forced expiratory maneuver by standard spirometry
description: Week 24 ± 1
measure: Change in forced lung capacity (FVC) compared to baseline
time frame: Week 24 ± 1
description: FVC - forced lung capacity by standard spirometry
measure: The number of exacerbations of chronic pulmonary disease
time frame: Week 24 ± 1
description: Clinical symptoms of chronic pulmonary disease exacerbation required antibiotic therapy in CF patients, include the presence of at least 4 of 12 possible signs or symptoms
A change in color or amount of sputum;
The appearance or intensification of hemoptysis;
Strengthening cough;
Increased shortness of breath;
Increased malaise, fatigue or lethargy;
Temperature above 38 ° C;
Anorexia or weight loss;
Sinuses pain or soreness;
Changes in the nature of sinuses mucus;
Changes in chest physical examination;
Pulmonary function decrease at list 10% or more;
Radiographic changes.
measure: The number of days before the chronic pulmonary disease exacerbation development
time frame: Week 24 ± 1
measure: Change in body weight compared to baseline
time frame: Week 24 ± 1
measure: Change in the average score for the "Symptoms", "Activity", "Influence" subscales, as well as the average total score of the St. George's Respiratory Questionnaire (SGRQ), version 2.2
time frame: Week 24 ± 1
description: St. George's Respiratory Questionnaire (SGRQ), a questionnaire for patients with respiratory diseases is designed to assess the chronic obstructive pulmonary disease patients quality of life.
The questionnaire consists of 76 questions, which are grouped in 3 parts:
The first part - symptoms - measures the degree of anxiety caused by respiratory symptoms.
The second part - activity - measures the limitation of mobility and physical activity.
The third part - the influence - evaluates the existing psychosocial consequences of bronchial obstruction.
arm group label: Tigerase®
arm group type: Experimental
description: Dornase alfa
arm group label: Pulmozyme®
arm group type: Active Comparator
description: Dornase alfa
intervention type: Biological
intervention name: Tigerase®
description: 2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days
arm group label: Tigerase®
other name: dornase alfa
intervention type: Biological
intervention name: Pulmozyme®
description: 2.5 mL (2.5 mg) dornase alfa nebulized once daily for 168 (+/-7) days
arm group label: Pulmozyme®
other name: dornase alfa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Oksana A. Markova, MD
role: Study Chair
affiliation: AO GENERIUM
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
sharing ipd: No