<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/NCT02255604</url>
  </required_header>
  <id_info>
    <org_study_id>ILIT</org_study_id>
    <nct_id>NCT02255604</nct_id>
  </id_info>
  <brief_title>Effect of Intralymphatic Immunotherapy</brief_title>
  <official_title>Effect of Intralymphatic Immunotherapy at Basophil Response and Plasmacell Kinetic in Patients With Allergic Rhinitis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators want to investigate whether specific immunotherapy can be delivered&#xD;
      directly into a lymph node. The investigators think that a direct introduction of allergen to&#xD;
      the antigen presenting cells in the lymph node a give a strong immune response and that this&#xD;
      can change the number of injections needed in allergen immunotherapy. The investigators do&#xD;
      measurements of clinical effect and a variety of paraclinical test to see if the&#xD;
      investigators can find af biomarker of successful specific immune therapy of grass allergy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients are injected with 3 or 4 doses of alk 225 Phleum Pratense 1000 standard quantity&#xD;
      units/ml in a lymph node in the groin.&#xD;
&#xD;
      The investigators monitor clinical response and use of medication during the grass pollen&#xD;
      season. SMS (Symptom and Medication Score) will be used.&#xD;
&#xD;
      The investigators count the number of immunoglobulin E grass producing plasma cells in blood&#xD;
      one week after each injection. The investigators also do basophil activation tests, nasal&#xD;
      provocation tests and titrated skin prick test to monitor effect.&#xD;
&#xD;
      Adverse events will be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2013</start_date>
  <completion_date type="Actual">February 1, 2017</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Change in cSMS (Combined Symptom and Medication Score)</measure>
    <time_frame>3 years</time_frame>
    <description>cSMS, Combined symptom and medication score, during grass pollen season in three years follow up.&#xD;
Minimal score 0, Maximal score 18. Higher score means worse outcome.&#xD;
Scale:&#xD;
Itchy/red eys: 0-3, Runny eyes: 0-3, Itchy nose: 0-3, Runny nose: 0-3, Block nose: 0-3, Sneezes: 0-3. Topical antihistamine 1.5 points/1 point. Nasal corticosteroid: 1 point/2 points. Oral antihistamine: 6 points/1 point. Oral prednisolon 1.5 point /3 points.&#xD;
Elements are summed to a combined score. Different combination methods exists. EAACI recommends means, i.e. symptoms 0-3 plus medicationscore 0-3. This scoringsystem was applied in the last follow-up year.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells</measure>
    <time_frame>one week from vaccinations</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Basophil Sensitivity</measure>
    <time_frame>2 years</time_frame>
    <description>Flowcytometry based analysis of basophil cells reaction to allergen provocation.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Allergy</condition>
  <condition>Immune Tolerance</condition>
  <condition>Injection Site Discomfort</condition>
  <arm_group>
    <arm_group_label>intralymphatic immune therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3 intralymphatic immune therapy</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>no intralymphatic immune therapy</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.</intervention_name>
    <description>4</description>
    <arm_group_label>intralymphatic immune therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.</intervention_name>
    <description>3 injection into a lymphnode</description>
    <arm_group_label>3 intralymphatic immune therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.1 ml Isoton saline</intervention_name>
    <description>4 injection into a lymphnode</description>
    <arm_group_label>no intralymphatic immune therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Allergic rhinitis to grass pollen, more than 3 mm reaction at skin prick test for&#xD;
             grass, age between 18 and 40 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled asthma.&#xD;
&#xD;
          -  Severe asthma with post bronchodilator test forced expiratory volume at 1 second less&#xD;
             than 70% of expected.&#xD;
&#xD;
          -  Severe co morbidity. Allergy to Fenol or Aluminium hydroxid.&#xD;
&#xD;
          -  Any autoimmune diseases. Treatment with beta blocking medicine.&#xD;
&#xD;
          -  Any heart diseases.&#xD;
&#xD;
          -  Severe arterial hypertension. Kidney failure.&#xD;
&#xD;
          -  Known malignancy. Known pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Søren Helbo SH Skaarup, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lungemedicinsk forskningsafdeling. Aarhus University Hospital.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lungemedicinsk Forskningsafdeling. Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2014</study_first_posted>
  <results_first_submitted>November 10, 2020</results_first_submitted>
  <results_first_submitted_qc>February 24, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 18, 2021</results_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Allergic Rhinitis</keyword>
  <keyword>Allergen immunotherapy</keyword>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.&#xD;
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4</description>
        </group>
        <group group_id="P2">
          <title>3 Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.&#xD;
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode</description>
        </group>
        <group group_id="P3">
          <title>no Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.&#xD;
0.1 ml Isoton saline: 4 injection into a lymphnode</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.&#xD;
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4</description>
        </group>
        <group group_id="B2">
          <title>3 Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.&#xD;
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode</description>
        </group>
        <group group_id="B3">
          <title>no Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.&#xD;
0.1 ml Isoton saline: 4 injection into a lymphnode</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.67" spread="5.52"/>
                    <measurement group_id="B2" value="29.92" spread="6.80"/>
                    <measurement group_id="B3" value="30.58" spread="7.43"/>
                    <measurement group_id="B4" value="30.72" spread="6.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in cSMS (Combined Symptom and Medication Score)</title>
        <description>cSMS, Combined symptom and medication score, during grass pollen season in three years follow up.&#xD;
Minimal score 0, Maximal score 18. Higher score means worse outcome.&#xD;
Scale:&#xD;
Itchy/red eys: 0-3, Runny eyes: 0-3, Itchy nose: 0-3, Runny nose: 0-3, Block nose: 0-3, Sneezes: 0-3. Topical antihistamine 1.5 points/1 point. Nasal corticosteroid: 1 point/2 points. Oral antihistamine: 6 points/1 point. Oral prednisolon 1.5 point /3 points.&#xD;
Elements are summed to a combined score. Different combination methods exists. EAACI recommends means, i.e. symptoms 0-3 plus medicationscore 0-3. This scoringsystem was applied in the last follow-up year.</description>
        <time_frame>3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.&#xD;
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4</description>
          </group>
          <group group_id="O2">
            <title>3 Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.&#xD;
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode</description>
          </group>
          <group group_id="O3">
            <title>no Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.&#xD;
0.1 ml Isoton saline: 4 injection into a lymphnode</description>
          </group>
        </group_list>
        <measure>
          <title>Change in cSMS (Combined Symptom and Medication Score)</title>
          <description>cSMS, Combined symptom and medication score, during grass pollen season in three years follow up.&#xD;
Minimal score 0, Maximal score 18. Higher score means worse outcome.&#xD;
Scale:&#xD;
Itchy/red eys: 0-3, Runny eyes: 0-3, Itchy nose: 0-3, Runny nose: 0-3, Block nose: 0-3, Sneezes: 0-3. Topical antihistamine 1.5 points/1 point. Nasal corticosteroid: 1 point/2 points. Oral antihistamine: 6 points/1 point. Oral prednisolon 1.5 point /3 points.&#xD;
Elements are summed to a combined score. Different combination methods exists. EAACI recommends means, i.e. symptoms 0-3 plus medicationscore 0-3. This scoringsystem was applied in the last follow-up year.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" lower_limit="1.8" upper_limit="3.4"/>
                    <measurement group_id="O2" value="2.3" lower_limit="1.5" upper_limit="3.0"/>
                    <measurement group_id="O3" value="4.5" lower_limit="3" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells</title>
        <time_frame>one week from vaccinations</time_frame>
        <population>Due to technical flow-cytometry problem could analysis of circulating grass specific immunoglobulin E producing plasma cells not be performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.&#xD;
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4</description>
          </group>
          <group group_id="O2">
            <title>3 Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.&#xD;
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode</description>
          </group>
          <group group_id="O3">
            <title>no Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.&#xD;
0.1 ml Isoton saline: 4 injection into a lymphnode</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells</title>
          <population>Due to technical flow-cytometry problem could analysis of circulating grass specific immunoglobulin E producing plasma cells not be performed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Basophil Sensitivity</title>
        <description>Flowcytometry based analysis of basophil cells reaction to allergen provocation.</description>
        <time_frame>2 years</time_frame>
        <population>Due to technical problems data was not recorded at all time points and results are missing.</population>
        <group_list>
          <group group_id="O1">
            <title>Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.&#xD;
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4</description>
          </group>
          <group group_id="O2">
            <title>3 Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.&#xD;
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode</description>
          </group>
          <group group_id="O3">
            <title>no Intralymphatic Immune Therapy</title>
            <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.&#xD;
0.1 ml Isoton saline: 4 injection into a lymphnode</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Basophil Sensitivity</title>
          <description>Flowcytometry based analysis of basophil cells reaction to allergen provocation.</description>
          <population>Due to technical problems data was not recorded at all time points and results are missing.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.&#xD;
Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 4</description>
        </group>
        <group group_id="E2">
          <title>3 Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.&#xD;
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.&#xD;
alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.: 3 injection into a lymphnode</description>
        </group>
        <group group_id="E3">
          <title>no Intralymphatic Immune Therapy</title>
          <description>Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.&#xD;
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.&#xD;
0.1 ml Isoton saline: 4 injection into a lymphnode</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <description>Headache, fatigue</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>anaphylaxis</sub_title>
                <description>anaphylaxis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Local reaction</sub_title>
                <description>Local swelling, edema and rubor at injection point</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Hans Jürgen Hoffmann</name_or_title>
      <organization>Aarhus Universitets Hospital</organization>
      <phone>7845000</phone>
      <email>Hans.Jurgen.Hoffmann@ki.au.dk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02255604
org study id: ILIT
nct id: NCT02255604
lead sponsor: 
has dmc: Yes
The investigators want to investigate whether specific immunotherapy can be delivered
      directly into a lymph node. The investigators think that a direct introduction of allergen to
      the antigen presenting cells in the lymph node a give a strong immune response and that this
      can change the number of injections needed in allergen immunotherapy. The investigators do
      measurements of clinical effect and a variety of paraclinical test to see if the
      investigators can find af biomarker of successful specific immune therapy of grass allergy.
Patients are injected with 3 or 4 doses of alk 225 Phleum Pratense 1000 standard quantity
      units/ml in a lymph node in the groin.

      The investigators monitor clinical response and use of medication during the grass pollen
      season. SMS (Symptom and Medication Score) will be used.

      The investigators count the number of immunoglobulin E grass producing plasma cells in blood
      one week after each injection. The investigators also do basophil activation tests, nasal
      provocation tests and titrated skin prick test to monitor effect.

      Adverse events will be recorded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in cSMS (Combined Symptom and Medication Score)
time frame: 3 years
description: cSMS, Combined symptom and medication score, during grass pollen season in three years follow up.
Minimal score 0, Maximal score 18. Higher score means worse outcome.
Scale:
Itchy/red eys: 0-3, Runny eyes: 0-3, Itchy nose: 0-3, Runny nose: 0-3, Block nose: 0-3, Sneezes: 0-3. Topical antihistamine 1.5 points/1 point. Nasal corticosteroid: 1 point/2 points. Oral antihistamine: 6 points/1 point. Oral prednisolon 1.5 point /3 points.
Elements are summed to a combined score. Different combination methods exists. EAACI recommends means, i.e. symptoms 0-3 plus medicationscore 0-3. This scoringsystem was applied in the last follow-up year.
measure: Change in Circulating Grass Specific Immunoglobulin E Producing Plasmacells
time frame: one week from vaccinations
measure: Change in Basophil Sensitivity
time frame: 2 years
description: Flowcytometry based analysis of basophil cells reaction to allergen provocation.
arm group label: intralymphatic immune therapy
arm group type: Active Comparator
description: Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015.
arm group label: 3 intralymphatic immune therapy
arm group type: Placebo Comparator
description: Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of alk 225 Phleum Pratense 10,000 standard quantity units/ml.
Patients receive 3 injection in total. 3 injection in the spring 2014 with one month interval. In in the spring 2015 patients will have a placebo injection.
arm group label: no intralymphatic immune therapy
arm group type: Sham Comparator
description: Lymphnodes in the groin are identified with ultrasound. Under ultrasound guide they are injected with 0,1 ml of isotone saline.
Patients receive 4 injection in total. 3 injection in the spring 2014 with one month interval and 1 injection in the spring 2015. All injections are with isotone saline as placebo control.
intervention type: Drug
intervention name: Alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.
description: 4
arm group label: intralymphatic immune therapy
intervention type: Drug
intervention name: alk (225) Phleum Pratense. 0.1 ml of 10,000 standard quantity units/ml.
description: 3 injection into a lymphnode
arm group label: 3 intralymphatic immune therapy
intervention type: Drug
intervention name: 0.1 ml Isoton saline
description: 4 injection into a lymphnode
arm group label: no intralymphatic immune therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Søren Helbo SH Skaarup, MD
role: Principal Investigator
affiliation: Lungemedicinsk forskningsafdeling. Aarhus University Hospital.
facility: 
country: Denmark
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 