<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/NCT01682070</url>
  </required_header>
  <id_info>
    <org_study_id>SP/0036</org_study_id>
    <nct_id>NCT01682070</nct_id>
  </id_info>
  <brief_title>SUBLIVAC FIX Phleum Pratense DT/DRF</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study to Determine Safety, Tolerability and the Optimal Effective Dose of SUBLIVAC FIX Phleum Pratense in Patients With Allergic Rhinitis/Rhinoconjunctivitis Caused by Grass Pollen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HAL Allergy</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>HAL Allergy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to determine the optimal effective dose of SUBLIVAC FIX Phleum&#xD;
      pratense based on reduction of upper airways reactivity after 5 months of treatment with&#xD;
      different dosages of SUBLIVAC FIX Phleum pratense compared to placebo. Furthermore, safety&#xD;
      and tolerability will be assessed by the number of related Adverse Events of different&#xD;
      dosages of SUBLIVAC FIX Phleum pratense compared to placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>Phase 2</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>Nasal Provocation Test (NPT)</measure>
    <time_frame>5 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of related AEs</measure>
    <time_frame>First ten days of study medication intake</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum specific immunoglobulin levels (IgE, IgG, IgG4)</measure>
    <time_frame>5 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of local and systemic reactions</measure>
    <time_frame>Duration of study medication intake (approximately 5 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Nasal Inspiratory Flow (PNIF)</measure>
    <time_frame>5 months</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">266</enrollment>
  <condition>Allergic Rhinitis</condition>
  <condition>Allergic Rhinoconjunctivitis</condition>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX Phleum prat. 0 AUN/ml</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX Phleum prat. 3,333 AUN/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX phleum prat. 10,000 AUN/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX phleum prat. 20,000 AUN/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Evaluation of the SUBLIVAC FIX Phleum prat. 20,000 AUN/ml by an independent safety committee</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX Phleum prat. 40,000 AUN/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Start of SUBLIVAC FIX Phleum prat. 40,000 AUN/ml arm depends on safety in the SUBLIVAC FIX Phleum prat. 20,000 AUN/ml arm evaluated by an independent safety committee</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SUBLIVAC FIX phleum prat.</intervention_name>
    <description>Comparison of different dosages to placebo</description>
    <arm_group_label>SUBLIVAC FIX Phleum prat. 3,333 AUN/ml</arm_group_label>
    <arm_group_label>SUBLIVAC FIX Phleum prat. 40,000 AUN/ml</arm_group_label>
    <arm_group_label>SUBLIVAC FIX phleum prat. 10,000 AUN/ml</arm_group_label>
    <arm_group_label>SUBLIVAC FIX phleum prat. 20,000 AUN/ml</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>SUBLIVAC FIX Phleum prat. 0 AUN/ml</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Age ≥ 18 ≤ 60 years&#xD;
&#xD;
          -  Allergic rhinitis/rhinoconjunctivitis related to grass pollen with or without&#xD;
             concomitant mild to moderate persistent asthma&#xD;
&#xD;
          -  FEV1 &gt; 70% for patients with a history of asthma, FEV &gt; 70% or PEF &gt; 80% for patients&#xD;
             without a history of asthma&#xD;
&#xD;
          -  A positive SPT (mean wheal diameter ≥ 3mm compared to negative control and negative&#xD;
             control should be negative) for grass pollen assessed within 1 year before&#xD;
             randomization.&#xD;
&#xD;
          -  Positive serum specific anti-grass IgE-test (&gt; 0.7 U/mL)&#xD;
&#xD;
          -  A positive TNPT for grass pollen at screening (Lebel score ≥ 6) at ≤10,000 AU/mL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with (expected) clinically relevant symptoms during the course of the trial&#xD;
             due to concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3mm) to&#xD;
             allergens other than grass pollen&#xD;
&#xD;
          -  Patients sensitized to pets should not be included if they are regularly exposed to&#xD;
             pets and are symptomatic upon exposure to pets&#xD;
&#xD;
          -  Completed immunotherapy (SCIT or SLIT) with grass pollen allergens within the past 5&#xD;
             years&#xD;
&#xD;
          -  Completed unsuccessful specific immunotherapy in the past&#xD;
&#xD;
          -  Vaccination within one week before start of therapy or during the initiation phase&#xD;
&#xD;
          -  Anti-IgE therapy within the 6 months prior to inclusion and during the study&#xD;
&#xD;
          -  Severe immune disorders (including auto-immune diseases) and/or diseases requiring&#xD;
             immunosuppressive drugs&#xD;
&#xD;
          -  Active malignancies or any malignant disease during the previous 5 years&#xD;
&#xD;
          -  Severe uncontrolled diseases that could increase the risk for patients participating&#xD;
             in the study, including but not limited to: cardiovascular insufficiency, any severe&#xD;
             or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic&#xD;
             diseases, or haematological disorders&#xD;
&#xD;
          -  Active inflammation or infection of the target organs (nose, eyes or lower airways) at&#xD;
             the start of the study&#xD;
&#xD;
          -  Moderate to severe nasal obstructive diseases that preclude a TNPT (septal deviation,&#xD;
             nasal polyps, recent nasal surgery, etc.)&#xD;
&#xD;
          -  Diseases with a contraindication for the use of Adrenaline (e.g. hyperthyroidism,&#xD;
             glaucoma)&#xD;
&#xD;
          -  Use of systemic steroids within 4 weeks before start of the study and during the study&#xD;
&#xD;
          -  Treatment with systemic and local β-blockers&#xD;
&#xD;
          -  Participation in a clinical study with a new investigational drug within the last 3&#xD;
             months or for a biological within the last 6 months prior to or during the study&#xD;
&#xD;
          -  Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing&#xD;
             age (adequate contraceptive measures will be the use of a contraceptive device or&#xD;
             -pill)&#xD;
&#xD;
          -  Alcohol, drug or medication abuse within the past year&#xD;
&#xD;
          -  Any clinically significant abnormal laboratory parameter at screening&#xD;
&#xD;
          -  Lack of cooperation or compliance&#xD;
&#xD;
          -  Severe psychiatric, psychological, or neurological disorders&#xD;
&#xD;
          -  Patients who are employees of the institution or 1st grade relatives or partners of&#xD;
             the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Walter G. Canonica, Prof. Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>Allergy and Respiratory Diseases University of Genoa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CIMS Studienzentrum Bamberg</name>
      <address>
        <city>Bamberg</city>
        <zip>96049</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Universitaetsmedizin Berlin Klinik f. Dermatalogie, Venerologie u. Allergologie, Campus Charité Mitte</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik u. Poliklinik f. Dermatologie u. Allergologie Universität Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatologikum Hamburg - Dept. of Allergology</name>
      <address>
        <city>Hamburg</city>
        <zip>20354</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HNO Praxis Dr. Horn/Dr. Zeuner</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Johann-Wolfgang-Goethe Universität - Zentrum f. Kinder- u. Jugendmedizin</name>
      <address>
        <city>Hessen</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dres.Ina Röhrig-Petering und Holger Petering</name>
      <address>
        <city>Hildesheim</city>
        <zip>31134</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FÄ HNO Allergologie</name>
      <address>
        <city>Saalfeld /Saale</city>
        <zip>07318</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Stuttgart - Klinik f. Dermatologie u. Allergologie</name>
      <address>
        <city>Stuttgart</city>
        <zip>70174</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitäts- Hautklinik Eberhard Karls - Universität Tübingen Department of Dermatology</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dr. Med. Ulrich Neumann</name>
      <address>
        <city>Wolmirstedt</city>
        <zip>393 26</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny</name>
      <address>
        <city>Białystok</city>
        <zip>15-430</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SP-ZOZ Ośrodek Zdrowia w Bieńkówce</name>
      <address>
        <city>Bieńkówka</city>
        <zip>PL-34 212</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOS &quot;Zdrowie&quot;</name>
      <address>
        <city>Cieszyn</city>
        <zip>43-400</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poradnia Alergologiczna Samodzielnego Publicznego Szpitala Nr 5 Slaskiego Uniwersytetu Medycznego w Katowicach</name>
      <address>
        <city>Katowice</city>
        <zip>40-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poradnia Alergologii i Chorób Płuc SP ZOZ Uniwersytecki Szpital Kliniczny im Norberta Barlickiego w Łodzi</name>
      <address>
        <city>Lodz</city>
        <zip>90-153</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ALERGOPNEUMA Marek Michnar i Wspolnicy Sp. Jawna</name>
      <address>
        <city>Lublin</city>
        <zip>20-089</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Centrum Alergologii</name>
      <address>
        <city>Lublin</city>
        <zip>20-522</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Alergologii Teresa Hofman</name>
      <address>
        <city>Poznań</city>
        <zip>60-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ALERGOMED Specjalistyczna Przychodnia Lekarska Sp. z o.o.</name>
      <address>
        <city>Tarnów</city>
        <zip>33-100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EMC Intytut Medyczny S.A. Przychodnia przy Łowieckiej</name>
      <address>
        <city>Wrocław</city>
        <zip>50-220</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Lekarze Specjaliści J. Małolepszy i Partnerzy</name>
      <address>
        <city>Wrocław</city>
        <zip>50-434</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Centrum Alergologii</name>
      <address>
        <city>Łódź</city>
        <zip>90-553</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Poland</country>
  </location_countries>
  <verification_date>May 2013</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>May 28, 2013</last_update_submitted>
  <last_update_submitted_qc>May 28, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 29, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sublingual immunotherapy</keyword>
  <keyword>Dose range finding</keyword>
  <keyword>Dose tolerability</keyword>
  <keyword>grass pollen</keyword>
  <keyword>Allergic rhinitis/rhinoconjunctivitis</keyword>
  <keyword>Safety</keyword>
  <keyword>Immunogenicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhinitis</mesh_term>
    <mesh_term>Rhinitis, Allergic</mesh_term>
    <mesh_term>Conjunctivitis</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/NCT01682070
org study id: SP/0036
nct id: NCT01682070
lead sponsor: 
has dmc: Yes
The aim of the study is to determine the optimal effective dose of SUBLIVAC FIX Phleum
      pratense based on reduction of upper airways reactivity after 5 months of treatment with
      different dosages of SUBLIVAC FIX Phleum pratense compared to placebo. Furthermore, safety
      and tolerability will be assessed by the number of related Adverse Events of different
      dosages of SUBLIVAC FIX Phleum pratense compared to placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Nasal Provocation Test (NPT)
time frame: 5 months
measure: Number of related AEs
time frame: First ten days of study medication intake
measure: Serum specific immunoglobulin levels (IgE, IgG, IgG4)
time frame: 5 months
measure: Number of local and systemic reactions
time frame: Duration of study medication intake (approximately 5 months)
measure: Peak Nasal Inspiratory Flow (PNIF)
time frame: 5 months
arm group label: SUBLIVAC FIX Phleum prat. 0 AUN/ml
arm group type: Placebo Comparator
arm group label: SUBLIVAC FIX Phleum prat. 3,333 AUN/ml
arm group type: Experimental
arm group label: SUBLIVAC FIX phleum prat. 10,000 AUN/ml
arm group type: Experimental
arm group label: SUBLIVAC FIX phleum prat. 20,000 AUN/ml
arm group type: Experimental
description: Evaluation of the SUBLIVAC FIX Phleum prat. 20,000 AUN/ml by an independent safety committee
arm group label: SUBLIVAC FIX Phleum prat. 40,000 AUN/ml
arm group type: Experimental
description: Start of SUBLIVAC FIX Phleum prat. 40,000 AUN/ml arm depends on safety in the SUBLIVAC FIX Phleum prat. 20,000 AUN/ml arm evaluated by an independent safety committee
intervention type: Biological
intervention name: SUBLIVAC FIX phleum prat.
description: Comparison of different dosages to placebo
arm group label: SUBLIVAC FIX Phleum prat. 3,333 AUN/ml
arm group label: SUBLIVAC FIX Phleum prat. 40,000 AUN/ml
arm group label: SUBLIVAC FIX phleum prat. 10,000 AUN/ml
arm group label: SUBLIVAC FIX phleum prat. 20,000 AUN/ml
intervention type: Biological
intervention name: Placebo
arm group label: SUBLIVAC FIX Phleum prat. 0 AUN/ml
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Walter G. Canonica, Prof. Dr.
role: Study Chair
affiliation: Allergy and Respiratory Diseases University of Genoa
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country: Germany
country: Poland
responsible party type: Sponsor
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
mesh term: Conjunctivitis