<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/NCT02975479</url>
  </required_header>
  <id_info>
    <org_study_id>2015-001259-63 substudy</org_study_id>
    <nct_id>NCT02975479</nct_id>
  </id_info>
  <brief_title>Intralymphatic Immunotherapy in Increasing Doses, Substudy</brief_title>
  <official_title>Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U - a Human Randomized Clinical Trial. Substudy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Skane University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study evaluates the safety and effect of intralymphatic allergen specific immunotherapy&#xD;
      in increasing doses. Patients with allergy to grass or birch will be treated with three&#xD;
      intralymphatic injections in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or&#xD;
      placebo.&#xD;
&#xD;
      ***IMPORTANT INFORMATION!*** The up-dosing protocol is changed due to adverse events at 5000&#xD;
      SQ-U. One patient had general utricaria 15 minutes after injection (moderate reaction). One&#xD;
      patient had a serious adverse event with anaphylactic reaction 6 minutes after intralymphatic&#xD;
      injection. (1000 SQ-U and 3000 SQ-U have been given with no serious adverse events.) New&#xD;
      regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      40 patients with seasonal allergic rhinitis will be recruited. Study subjects are randomized&#xD;
      to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch. Injections are&#xD;
      given with 4-5 (-7) weeks interval.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2016</start_date>
  <completion_date type="Actual">June 20, 2022</completion_date>
  <primary_completion_date type="Actual">June 20, 2022</primary_completion_date>
  <phase>Phase 2/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>Mean combined daily symptoms-and-medications-score</measure>
    <time_frame>Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).</time_frame>
    <description>Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) and medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean total daily symptoms score</measure>
    <time_frame>Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).</time_frame>
    <description>Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean total daily medications score</measure>
    <time_frame>Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).</time_frame>
    <description>Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in subjective allergic symptoms following nasal allergen provocation</measure>
    <time_frame>Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.</time_frame>
    <description>The study subjects will be intranasally challenged with allergen and symptom score questionnaires are filled out pre-provocation and 5, 10 and 30 min post-provocation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects on quality of life</measure>
    <time_frame>During peak pollen season which will be up to 6 months after completed treatment.</time_frame>
    <description>Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Short term change of skin reactivity</measure>
    <time_frame>Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.</time_frame>
    <description>Skin prick test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>S-IgE Grass or Birch</measure>
    <time_frame>Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>S-IgG4 Grass or Birch</measure>
    <time_frame>Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Registration of adverse event</measure>
    <time_frame>From the first injection to 30 days after the last injections has been given</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Rhinitis, Allergic, Seasonal</condition>
  <arm_group>
    <arm_group_label>Intralymphatic placebo injections</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intralymphatic active injections</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ATC-code V01AA02. 3 injections with 4-7 weeks interval in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U, 10000 SQ-U.&#xD;
***IMPORTANT INFORMATION! The up-dosing protocol is changed due to an adverse event at the last injection. New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U. ***</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALK Diluent</intervention_name>
    <arm_group_label>Intralymphatic placebo injections</arm_group_label>
    <other_name>0,3% human albumin. ATC-code V07AB</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ALK Alutard SQ 5-grasses or ALK Alutard Birch</intervention_name>
    <description>Depot formulation of relevant allergen adsorbed to aluminium hydroxide in a suspension.</description>
    <arm_group_label>Intralymphatic active injections</arm_group_label>
    <other_name>Allergen, grass pollen. ATC-code V01AA02 or V01AA05</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Seasonal allergic symptoms for birch and/or grass verified by skin prick test,&#xD;
&#xD;
          -  Accepted informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or nursing&#xD;
&#xD;
          -  Autoimmune or collagen disease (known)&#xD;
&#xD;
          -  Cardiovascular disease&#xD;
&#xD;
          -  Perennial pulmonary disease&#xD;
&#xD;
          -  Hepatic disease&#xD;
&#xD;
          -  Renal disease&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Any medication with a possible side-effect of interfering with the immune response&#xD;
&#xD;
          -  Previous immuno- or chemotherapy&#xD;
&#xD;
          -  Chronic diseases&#xD;
&#xD;
          -  Other upper airway disease (non-allergic sinusitis, nasal polyps, chronic obstructive&#xD;
             and restrictive lung disease)&#xD;
&#xD;
          -  Disease or conditions rendering the treatment of anaphylactic reactions difficult&#xD;
             (symptomatic coronary heart diseases, severe arterial hypertension and treatment with&#xD;
             β-blockers)&#xD;
&#xD;
          -  Major metabolic disease&#xD;
&#xD;
          -  Known or suspected allergy to the study product&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Mental incapability of coping with the study&#xD;
&#xD;
          -  Withdrawal of informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lars-Olaf Cardell, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund</name>
      <address>
        <city>Lund</city>
        <zip>221 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)</name>
      <address>
        <city>Stockholm</city>
        <zip>141 86</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 24, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>June 22, 2022</last_update_submitted>
  <last_update_submitted_qc>June 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Lars Olaf Cardell</investigator_full_name>
    <investigator_title>Professor, Head of Division, M.D.</investigator_title>
  </responsible_party>
  <keyword>Hay fever</keyword>
  <keyword>Pollen allergy</keyword>
  <keyword>Allergic rhinitis</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02975479
org study id: 2015-001259-63 substudy
nct id: NCT02975479
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The study evaluates the safety and effect of intralymphatic allergen specific immunotherapy
      in increasing doses. Patients with allergy to grass or birch will be treated with three
      intralymphatic injections in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or
      placebo.

      ***IMPORTANT INFORMATION!*** The up-dosing protocol is changed due to adverse events at 5000
      SQ-U. One patient had general utricaria 15 minutes after injection (moderate reaction). One
      patient had a serious adverse event with anaphylactic reaction 6 minutes after intralymphatic
      injection. (1000 SQ-U and 3000 SQ-U have been given with no serious adverse events.) New
      regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U.
40 patients with seasonal allergic rhinitis will be recruited. Study subjects are randomized
      to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch. Injections are
      given with 4-5 (-7) weeks interval.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean combined daily symptoms-and-medications-score
time frame: Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
description: Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) and medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).
measure: Mean total daily symptoms score
time frame: Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
description: Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)
measure: Mean total daily medications score
time frame: Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
description: Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).
measure: Change in subjective allergic symptoms following nasal allergen provocation
time frame: Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
description: The study subjects will be intranasally challenged with allergen and symptom score questionnaires are filled out pre-provocation and 5, 10 and 30 min post-provocation.
measure: Effects on quality of life
time frame: During peak pollen season which will be up to 6 months after completed treatment.
description: Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires
measure: Short term change of skin reactivity
time frame: Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
description: Skin prick test
measure: S-IgE Grass or Birch
time frame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: S-IgG4 Grass or Birch
time frame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: Registration of adverse event
time frame: From the first injection to 30 days after the last injections has been given
arm group label: Intralymphatic placebo injections
arm group type: Placebo Comparator
description: ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval.
arm group label: Intralymphatic active injections
arm group type: Active Comparator
description: ATC-code V01AA02. 3 injections with 4-7 weeks interval in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U, 10000 SQ-U.
***IMPORTANT INFORMATION! The up-dosing protocol is changed due to an adverse event at the last injection. New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U. ***
intervention type: Drug
intervention name: ALK Diluent
arm group label: Intralymphatic placebo injections
other name: 0,3% human albumin. ATC-code V07AB
intervention type: Drug
intervention name: ALK Alutard SQ 5-grasses or ALK Alutard Birch
description: Depot formulation of relevant allergen adsorbed to aluminium hydroxide in a suspension.
arm group label: Intralymphatic active injections
other name: Allergen, grass pollen. ATC-code V01AA02 or V01AA05
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Lars-Olaf Cardell, Professor
role: Principal Investigator
affiliation: Karolinska Institutet
facility: 
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Lars Olaf Cardell
investigator title: Professor, Head of Division, M.D.
mesh term: Rhinitis
mesh term: Rhinitis, Allergic
mesh term: Rhinitis, Allergic, Seasonal
sharing ipd: Undecided