<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/NCT01731249</url>
  </required_header>
  <id_info>
    <org_study_id>VO68.10</org_study_id>
    <secondary_id>2010-020693-42</secondary_id>
    <nct_id>NCT01731249</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of a Sublingual Immunotherapy Solution to Treat Patients Suffering From Birch Pollen Allergic Rhinoconjunctivitis</brief_title>
  <official_title>A Randomised, Double-blind, Placebo-controlled, Multi-national, Phase IIIb Study to Assess the Sustained Clinical Effect and Safety of Sublingual Immunotherapy Administered as Birch Pollen Extract Solution at a Dose of 300 IR Once Daily to Patients Suffering From Birch Pollen-induced Rhinoconjunctivitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stallergenes Greer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quintiles, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aptuit</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cenduit LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>PHT Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Stallergenes Greer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this 2-year study is to assess the sustained clinical efficacy and safety of&#xD;
      300 IR/day of a sublingual solution of birch pollen allergen extract starting 4 months prior&#xD;
      to the birch pollen season and continuing over the birch pollen season compared with placebo&#xD;
      for reduction of rhinoconjunctivitis-related symptoms and anti-allergy medication usage.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2010</start_date>
  <completion_date type="Actual">October 2012</completion_date>
  <primary_completion_date type="Actual">July 2012</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>Average Adjusted Symptom Score</measure>
    <time_frame>Year 2 of treatment</time_frame>
    <description>Symptom score adjusted on patient's rescue medication usage</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Average Rhinoconjunctivitis Total Symptom Score</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Rescue Medication Score</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Each of Six Individual Average Rhinoconjunctivitis Symptom Scores</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Combined Score</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Rhinoconjunctivitis Visual Analogue Scale Score</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Adjusted Visual Analogue Scale Score</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Medication Usage</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Symptom-controlled Days</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rhinoconjunctivitis Quality of Life Questionnaire</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global evaluation of the efficacy by the patient</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitization profile</measure>
    <time_frame>Before and after each treatment period (over 2 years)</time_frame>
    <description>sensitization profile (mono- vs poly-sensitized) is derived from the skin prick test results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asthma</measure>
    <time_frame>Before, during and after each pollen season (over 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological markers specific for birch pollen</measure>
    <time_frame>Before and after each treatment period (over 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Economical Evaluation</measure>
    <time_frame>Year 2 of treatment</time_frame>
    <description>Proportion of days-off due to birch pollen-induced symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wheal diameter of the birch allergen Skin prick test</measure>
    <time_frame>Before and after each treatment period (over 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Provocation Test</measure>
    <time_frame>Year 2 of treatment</time_frame>
    <description>Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucosa Local Inflammation</measure>
    <time_frame>Year 1 of treatment</time_frame>
    <description>Analysis on a subset of patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety assessments</measure>
    <time_frame>~20 months</time_frame>
    <description>adverse events, physical examination including vital signs and laboratory data described by number of patients in each treatment group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average adjusted Symptom score analysis by tertiles</measure>
    <time_frame>Year 2 of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">574</enrollment>
  <condition>Hypersensitivity</condition>
  <condition>Allergic Rhinitis</condition>
  <condition>Allergic Conjunctivitis</condition>
  <condition>Seasonal Allergy</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo sublingual solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Birch pollen allergen extract</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sublingual Solution of Birch pollen allergen extract 300IR once daily 5 months per year and during 2 years</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>10 actuations of placebo sublingual solution once daily 5 months a year and during 2 years</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Birch pollen allergen extract</intervention_name>
    <description>Sublingual solution of Birch pollen allergen extract 300IR (10 actuations) once daily 5 months per year and during 2 years</description>
    <arm_group_label>Birch pollen allergen extract</arm_group_label>
    <other_name>Staloral Birch</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Symptomatic birch pollen-related allergic rhinoconjunctivitis for at least the&#xD;
             previous 2 pollen seasons requiring intake of symptomatic treatment.&#xD;
&#xD;
          -  Sensitization to birch pollen demonstrated by a positive Skin Prick Test to birch&#xD;
             pollen with wheal diameter &gt; 3 mm and birch pollen allergens specific IgE levels ≥&#xD;
             0.70 kU/L.&#xD;
&#xD;
          -  RRTSS based on the previous or on the penultimate birch pollen season ≥ 12 out of a&#xD;
             maximum possible score of 18.&#xD;
&#xD;
          -  Patients with an FEV1 (Forced Expiratory Volume at one second) ≥ 80% of the predicted&#xD;
             value.&#xD;
&#xD;
          -  Patients who are willing to comply with the protocol.&#xD;
&#xD;
          -  Patients having given a signed informed consent before completing any study related&#xD;
             procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with symptoms of rhinitis/rhinoconjunctivitis during the birch pollen season&#xD;
             due to any other allergens (except alder and hazel). This includes patients with&#xD;
             symptomatic allergic rhinitis/rhinoconjunctivitis due to cat or dog allergens, and&#xD;
             living with these animals at home or at risk of frequent contacts with these animals&#xD;
             (family, friends etc.) during the course of the study.&#xD;
&#xD;
          -  Patient who previously received desensitization treatment to birch pollen and/or&#xD;
             another Betulaceae sp. (for example hazel or alder) within the previous 5 years.&#xD;
&#xD;
          -  Patients with ongoing treatment by immunotherapy with another allergen.&#xD;
&#xD;
          -  Pregnancy (positive pregnancy test), breast-feeding.&#xD;
&#xD;
          -  Female patients of childbearing potential planning a pregnancy during this study or&#xD;
             not using a medically accepted contraceptive method (hormonal birth control [orally,&#xD;
             injectable or by implant, for at least 2 months before enrolment], intrauterine&#xD;
             device, spermicide used with a male condom, bilateral tubal ligation, diaphragm with&#xD;
             spermicide, female condom, monogamous relationship with a vasectomised partner).&#xD;
&#xD;
          -  Patients planning to move during the study or planning to leave the area during the&#xD;
             birch pollen season for more than 1 week (7 consecutive days).&#xD;
&#xD;
          -  Patients with moderate or severe persistent asthma (GINA 3 or 4).&#xD;
&#xD;
          -  Patients with seasonal mild persistent asthma (GINA 2) necessitating treatment with&#xD;
             inhaled glucocorticosteroids at a dose level greater than 400 mcg budesonide&#xD;
             dose-equivalents.&#xD;
&#xD;
          -  Patients with any nasal or oral condition that could interfere with the efficacy or&#xD;
             safety assessments (such as nasal polyposis or oral inflammation).&#xD;
&#xD;
          -  Patients with severe immune deficiency.&#xD;
&#xD;
          -  Patients with a past or current disease, which as judged by the Investigator, may&#xD;
             affect the patient's participation in or outcome of this study.&#xD;
&#xD;
          -  Any other disease or condition which would place a patient at undue risk by being&#xD;
             included in the study (according to the Investigator's opinion).&#xD;
&#xD;
          -  Usual contra-indications of immunotherapy such as concomitant beta-blocker therapy&#xD;
             whatever the route and/or immunosuppressive drugs.&#xD;
&#xD;
          -  Patients treated with inhaled/systemic steroids (whatever the indication) within 4&#xD;
             weeks prior to Visit 1 (Screening), or with long acting systemic corticosteroids 12&#xD;
             weeks before Visit 1 (Screening).&#xD;
&#xD;
          -  Patients under continuous corticotherapy (inhaled or systemic drugs).&#xD;
&#xD;
          -  Patients following a strict low sodium diet as the study treatment contains 590 mg of&#xD;
             sodium chloride per vial in a 10 mL solution.&#xD;
&#xD;
          -  Investigators, co-Investigators, as well as their children or spouses and all study&#xD;
             collaborators.&#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>Margitta WORM, MD, PR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité Campus Mitte, Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alergologicka ordinace</name>
      <address>
        <city>Plzen</city>
        <zip>30100</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital - Allergy Unit 4222</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merekivi Perearstid OÜ</name>
      <address>
        <city>Tallinn</city>
        <zip>10617</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsingin yliopistollinen keskussairaala</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHC, Hôpitaux Universitaires de Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Berlin - Allergie-Centrum-Charité</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre of Investigations and Treatment of Allergic Diseases</name>
      <address>
        <city>Riga</city>
        <zip>1003</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allergic Diseases Diagnostics and Treatment Centre</name>
      <address>
        <city>Vilnius</city>
        <zip>08109</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPZOZ Uniwersytecki Szpital Kliniczny Nr 1im.N.Barlickiego w Uniwersystetu Medycznego w Łodzi</name>
      <address>
        <city>Lodz</city>
        <zip>90-153</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imunologicko-alergologicka amb.</name>
      <address>
        <city>Banska Bystrica</city>
        <zip>975 17</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska Universitetssjukhuset - Avd för Lungmedicin och Allergi</name>
      <address>
        <city>Göteborg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czech Republic</country>
    <country>Denmark</country>
    <country>Estonia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Germany</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Poland</country>
    <country>Slovakia</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>November 22, 2012</last_update_submitted>
  <last_update_submitted_qc>November 22, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 27, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sublingual immunotherapy</keyword>
  <keyword>Birch pollen extract solution</keyword>
  <keyword>Allergic rhinoconjunctivitis</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>Rhinitis, Allergic, Seasonal</mesh_term>
    <mesh_term>Conjunctivitis</mesh_term>
    <mesh_term>Conjunctivitis, Allergic</mesh_term>
    <mesh_term>Hypersensitivity</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/NCT01731249
org study id: VO68.10
secondary id: 2010-020693-42
nct id: NCT01731249
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this 2-year study is to assess the sustained clinical efficacy and safety of
      300 IR/day of a sublingual solution of birch pollen allergen extract starting 4 months prior
      to the birch pollen season and continuing over the birch pollen season compared with placebo
      for reduction of rhinoconjunctivitis-related symptoms and anti-allergy medication usage.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Average Adjusted Symptom Score
time frame: Year 2 of treatment
description: Symptom score adjusted on patient's rescue medication usage
measure: Average Rhinoconjunctivitis Total Symptom Score
time frame: Year 2 of treatment
measure: Average Rescue Medication Score
time frame: Year 2 of treatment
measure: Each of Six Individual Average Rhinoconjunctivitis Symptom Scores
time frame: Year 2 of treatment
measure: Average Combined Score
time frame: Year 2 of treatment
measure: Average Rhinoconjunctivitis Visual Analogue Scale Score
time frame: Year 2 of treatment
measure: Average Adjusted Visual Analogue Scale Score
time frame: Year 2 of treatment
measure: Rescue Medication Usage
time frame: Year 2 of treatment
measure: Proportion of Symptom-controlled Days
time frame: Year 2 of treatment
measure: Rhinoconjunctivitis Quality of Life Questionnaire
time frame: Year 2 of treatment
measure: Global evaluation of the efficacy by the patient
time frame: Year 2 of treatment
measure: Sensitization profile
time frame: Before and after each treatment period (over 2 years)
description: sensitization profile (mono- vs poly-sensitized) is derived from the skin prick test results
measure: Asthma
time frame: Before, during and after each pollen season (over 2 years)
measure: Immunological markers specific for birch pollen
time frame: Before and after each treatment period (over 2 years)
measure: Economical Evaluation
time frame: Year 2 of treatment
description: Proportion of days-off due to birch pollen-induced symptoms
measure: Wheal diameter of the birch allergen Skin prick test
time frame: Before and after each treatment period (over 2 years)
measure: Oral Provocation Test
time frame: Year 2 of treatment
description: Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry
measure: Mucosa Local Inflammation
time frame: Year 1 of treatment
description: Analysis on a subset of patients
measure: Safety assessments
time frame: ~20 months
description: adverse events, physical examination including vital signs and laboratory data described by number of patients in each treatment group
measure: Average adjusted Symptom score analysis by tertiles
time frame: Year 2 of treatment
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo sublingual solution
arm group label: Birch pollen allergen extract
arm group type: Experimental
description: Sublingual Solution of Birch pollen allergen extract 300IR once daily 5 months per year and during 2 years
intervention type: Biological
intervention name: Placebo
description: 10 actuations of placebo sublingual solution once daily 5 months a year and during 2 years
arm group label: Placebo
intervention type: Biological
intervention name: Birch pollen allergen extract
description: Sublingual solution of Birch pollen allergen extract 300IR (10 actuations) once daily 5 months per year and during 2 years
arm group label: Birch pollen allergen extract
other name: Staloral Birch
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Margitta WORM, MD, PR
role: Principal Investigator
affiliation: Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité Campus Mitte, Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Czech Republic
country: Denmark
country: Estonia
country: Finland
country: France
country: Germany
country: Latvia
country: Lithuania
country: Poland
country: Slovakia
country: Sweden
responsible party type: Sponsor
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
mesh term: Rhinitis, Allergic, Seasonal
mesh term: Conjunctivitis
mesh term: Conjunctivitis, Allergic
mesh term: Hypersensitivity