<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/NCT02231307</url>
  </required_header>
  <id_info>
    <org_study_id>SB/0042</org_study_id>
    <nct_id>NCT02231307</nct_id>
  </id_info>
  <brief_title>SUBLIVAC FIX Birch Phase III Short-term Efficacy</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Clinical Efficacy and Safety of SUBLIVAC FIX Birch Immunotherapy in Patients Suffering From Allergic Rhinitis/Rhinoconjunctivitis Caused by Birch 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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this phase III study is to asses if SUBLIVAC FIX Birch is safe and effective in&#xD;
      reducing birch allergy induced symptoms and birch allergy medication usage.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>combined symptom medication score</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>symptom score</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life questionnaires</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum specific immunoglobulin levels</measure>
    <time_frame>up to 9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>local and systemic reactions</measure>
    <time_frame>up to 9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(serious) adverse events</measure>
    <time_frame>up to 9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>blood safety parameters</measure>
    <time_frame>up to 9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>urinalysis</measure>
    <time_frame>up to 9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>medication score</measure>
    <time_frame>up to 3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">406</enrollment>
  <condition>Birch Pollen Induced Rhinitis/Rhinoconjunctivitis</condition>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX Birch 0 AUN/ml</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>SUBLIVAC FIX Birch 40,000 AUN/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SUBLIVAC FIX Birch</intervention_name>
    <arm_group_label>SUBLIVAC FIX Birch 0 AUN/ml</arm_group_label>
    <arm_group_label>SUBLIVAC FIX Birch 40,000 AUN/ml</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Age ≥ 18 and ≤65 years&#xD;
&#xD;
          -  Moderate-to-severe birch pollen induced allergic rhinitis/rhinoconjunctivitis based on&#xD;
             ARIA classification for at least 2 consecutive years&#xD;
&#xD;
          -  FEV1 (forced expiratory volume at one second) &gt; 70% (of predicted value) for patients&#xD;
             with a history of asthma, FEV1 &gt; 70% or PEF (peak expiratory flow) &gt; 80% (of predicted&#xD;
             value) for patients without a history of asthma&#xD;
&#xD;
          -  Positive SPT (skin prick test) for birch pollen (mean wheal diameter ≥ 3mm compared to&#xD;
             negative control; negative control should be negative; histamine control should be&#xD;
             positive (mean wheal diameter ≥ 3mm)) assessed during screening.&#xD;
&#xD;
          -  Serum specific anti-birch IgE (immunoglobulin E) concentration &gt;0.7 U/ml&#xD;
&#xD;
          -  Patients should be willing and capable to complete an e-diary daily during the birch&#xD;
             pollen season (≥ 60% compliance in completion between Visit 1 and 2).&#xD;
&#xD;
          -  A positive Nasal Provocation Test to birch pollen at Visit 2 (Lebel score ≥ 6) or a&#xD;
             documented positive test within 1 year before start of treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients sensitized and symptomatic to pets should not be included if they are&#xD;
             regularly exposed to pets&#xD;
&#xD;
          -  Specific immunotherapy (SCIT or SLIT) with birch pollen or a cross-reacting allergen&#xD;
             within the last 5 years&#xD;
&#xD;
          -  SPT positive (mean wheal diameter ≥ 3mm compared to negative control; negative control&#xD;
             should be negative; histamine control should be positive (mean wheal diameter ≥ 3mm))&#xD;
             patients to allergen(s) other than birch pollen, in the absence of a negative&#xD;
             provocation test for this allergen(s) (within 1 year), who are expected to have&#xD;
             clinically relevant symptoms during the birch pollen season&#xD;
&#xD;
          -  Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the last&#xD;
             5 years&#xD;
&#xD;
          -  (Ongoing) allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) during&#xD;
             the study period&#xD;
&#xD;
          -  Vaccination one week before start of treatment and/or during the up-dosing phase&#xD;
&#xD;
          -  Treatment with experimental products within the last 3 months or biologicals&#xD;
             (including anti-IgE or TNF (tumor necrosis factor) - α treatment) within the last 6&#xD;
             months or during the study&#xD;
&#xD;
          -  Uncontrolled asthma or other active respiratory diseases&#xD;
&#xD;
          -  Clinically significant chronic sinusitis, ocular infection or severe inflammation of&#xD;
             the oral mucosa&#xD;
&#xD;
          -  Severe immune disorders (including auto-immune diseases) and/or diseases requiring&#xD;
             immunosuppressive drugs&#xD;
&#xD;
          -  Active malignancies or any malignant disease in the last 5 years&#xD;
&#xD;
          -  Acute or chronic disease that in the opinion of the investigator is an additional risk&#xD;
             for the patients, including but not limited to the following: cardiovascular&#xD;
             insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically&#xD;
             significant renal or hepatic diseases, or haematological disorders&#xD;
&#xD;
          -  Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism,&#xD;
             glaucoma)&#xD;
&#xD;
          -  Use of systemic corticosteroids 4 weeks before the study&#xD;
&#xD;
          -  Treatment with systemic or local β-blockers&#xD;
&#xD;
          -  Known hypersensitivity to any of the excipients (Disodium phosphate dihydrate, Sodium&#xD;
             dihydrogen phosphate dehydrate, aminocaproic acid, Peppermint oil, Caramel Colorant or&#xD;
             Glycerol)&#xD;
&#xD;
          -  A positive urine pregnancy test, lactation or inadequate contraceptive methods&#xD;
             (adequate methods: oral contraceptives, IUD (intrauterine device), condom use and&#xD;
             having no sexual relationship with a man)&#xD;
&#xD;
          -  Alcohol-, drug or medication abuse&#xD;
&#xD;
          -  Lack of co-operation or compliance&#xD;
&#xD;
          -  Severe psychiatric, psychological, or neurological disorders&#xD;
&#xD;
          -  Any physical or mental condition that precludes administration or allergen-specific&#xD;
             immunotherapy, compliance or participation in a clinical trial&#xD;
&#xD;
          -  Patients who are employees of the department, 1st grade relatives, or partners of the&#xD;
             investigator&#xD;
&#xD;
          -  Patients who have planned holidays outside the country for more than 7 continuous days&#xD;
             during the defined pollen season (1st of March till 31st of May)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oliver Pfaar, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Zentrum für Rhinologie und Allergologie, An-den-Quellen-10, 65189 Wiesbaden, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cliniques universitaire St. Luc</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR Citadelle</name>
      <address>
        <city>Liege</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Liege</name>
      <address>
        <city>Liege</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alergologicka ambulance</name>
      <address>
        <city>Breclav</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AKI spol. s.r.o.</name>
      <address>
        <city>Brno</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alergologicka ambulance</name>
      <address>
        <city>Liberec</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ordinace Alergologie</name>
      <address>
        <city>Most</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Respiral s.r.o.</name>
      <address>
        <city>Plzen</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ustav imunologie a alergologie</name>
      <address>
        <city>Plzen</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kasmed s.r.o.</name>
      <address>
        <city>Tabor</city>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIMS Studienzentrum Bamberg</name>
      <address>
        <city>Bamberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite Universitatsmedizin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatologikum Hamburg</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HNO Gemeinschaftspraxis</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautarztpraxis fur Dermatologie &amp; asthetische medizin</name>
      <address>
        <city>Hildesheim</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis fur Atemwegserkrankungen</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FA HNOW Allergologie</name>
      <address>
        <city>Saalfeld/Saale</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praxis Dr. Jager</name>
      <address>
        <city>Schwabach</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik fur Dermatologie &amp; Allergologie</name>
      <address>
        <city>Stuttgart</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HNO Wiesbaden Institute for Allergology and Rhinology</name>
      <address>
        <city>Wiesbaden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny</name>
      <address>
        <city>Bialystok</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ ZLS Medex Sp. z o.o. Poradnia Alergologiczna</name>
      <address>
        <city>Bielsko-Biala</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SP-ZOZ Osrodek Zdrowia w Bienkowce</name>
      <address>
        <city>Bienkowka</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Clinica Vitae</name>
      <address>
        <city>Gdansk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grazyna Pulka Specjalistyczny Osrodek 'All-Med'</name>
      <address>
        <city>Krakow</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Centrum Alergologii Krzysztof Buczylko</name>
      <address>
        <city>Lodz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poradnia Alergologii i Chorob Pluc Uniwersytecki Szpital Kliniczny</name>
      <address>
        <city>Lodz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ Centrum Alergologii</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Przychodnia Alergologiczno-Pulmonologiczna ALERGOPNEUMA</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Alergologii Teresa Hofman</name>
      <address>
        <city>Poznan</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrumk Medyczne Lucyna i Andrzej Dymek</name>
      <address>
        <city>Strzelce Opolskie</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ALERGOMED Specjalistyczna Przychodnia Lekarska</name>
      <address>
        <city>Tarnow</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EMC Intytut Medyczny S.A. Przychodnia przy Lowieckiej</name>
      <address>
        <city>Wroclaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ALIAN s.r.o. Ambulancia alergologie a klinickej imunologie</name>
      <address>
        <city>Bardejov</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alerso s.r.o. Imunoalergologicka ambulancie</name>
      <address>
        <city>Kosice</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>STALERG s.r.o. Imunoalergologicka ambulancia</name>
      <address>
        <city>Kosice</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DANIMED, spol. s.r.o. Ambulancia klinkckej imunologie a alergologie</name>
      <address>
        <city>Levice</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EMED s.r.o. Alergoimunologicke centrum</name>
      <address>
        <city>Presov</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czech Republic</country>
    <country>Germany</country>
    <country>Poland</country>
    <country>Slovakia</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>September 22, 2016</last_update_submitted>
  <last_update_submitted_qc>September 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sublingual immunotherapy</keyword>
  <keyword>birch pollen</keyword>
  <keyword>allergic rhinitis / rhinoconjunctivitis</keyword>
  <keyword>efficacy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhinitis</mesh_term>
    <mesh_term>Conjunctivitis</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/NCT02231307
org study id: SB/0042
nct id: NCT02231307
lead sponsor: 
has dmc: No
The aim of this phase III study is to asses if SUBLIVAC FIX Birch is safe and effective in
      reducing birch allergy induced symptoms and birch allergy medication usage.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: combined symptom medication score
time frame: 3 months
measure: symptom score
time frame: 3 months
measure: Quality of Life questionnaires
time frame: 3 months
measure: Serum specific immunoglobulin levels
time frame: up to 9 months
measure: local and systemic reactions
time frame: up to 9 months
measure: (serious) adverse events
time frame: up to 9 months
measure: blood safety parameters
time frame: up to 9 months
measure: urinalysis
time frame: up to 9 months
measure: medication score
time frame: up to 3 months
arm group label: SUBLIVAC FIX Birch 0 AUN/ml
arm group type: Placebo Comparator
arm group label: SUBLIVAC FIX Birch 40,000 AUN/ml
arm group type: Experimental
intervention type: Drug
intervention name: SUBLIVAC FIX Birch
arm group label: SUBLIVAC FIX Birch 0 AUN/ml
arm group label: SUBLIVAC FIX Birch 40,000 AUN/ml
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Oliver Pfaar, Prof. Dr.
role: Principal Investigator
affiliation: Zentrum für Rhinologie und Allergologie, An-den-Quellen-10, 65189 Wiesbaden, Germany
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country: Belgium
country: Czech Republic
country: Germany
country: Poland
country: Slovakia
responsible party type: Sponsor
mesh term: Rhinitis
mesh term: Conjunctivitis
sharing ipd: No