<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/NCT02216175</url>
  </required_header>
  <id_info>
    <org_study_id>18SM4569</org_study_id>
    <secondary_id>18/LO/1070</secondary_id>
    <nct_id>NCT02216175</nct_id>
  </id_info>
  <brief_title>Improving the Safety of Oral Immunotherapy for Cow's Milk Allergy</brief_title>
  <acronym>SOCMA</acronym>
  <official_title>Phase 2/3 Clinical Trial to Assess the Effect of a Sublingual Treatment Phase Prior to Oral Immunotherapy in Children With Cow's Milk Allergy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>JP Moulton Charitable Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sociedad Española de Alergología e Inmunología</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Allergy to cow's milk is the most common food allergy affecting children. There is currently&#xD;
      no accepted routine clinical therapy to cure milk allergy. Recently studies have attempted to&#xD;
      induce desensitisation using small daily doses of cow's milk, predominantly by the oral route&#xD;
      (oral immunotherapy, OIT). Although this therapy works for some people, its effects are not&#xD;
      generally long lasting and it is associated with significant side effects during protocol,&#xD;
      including potentially life-threatening allergic reactions.&#xD;
&#xD;
      Pilot data suggests that sublingual immunotherapy (SLIT, where allergen is held under the&#xD;
      tongue, rather than swallowed) can also induce a degree of desensitisation, but with fewer&#xD;
      adverse events. However, the degree of desensitisation induced appears to be lower than that&#xD;
      with oral immunotherapy.&#xD;
&#xD;
      The investigators wish to determine whether a sublingual pretreatment phase can improve the&#xD;
      safety of conventional OIT in cow's milk allergy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 19, 2018</start_date>
  <completion_date type="Actual">January 19, 2022</completion_date>
  <primary_completion_date type="Actual">September 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events in participants</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of participants experiencing adverse events (excluding mild, non-transient symptoms) conventional OIT to cow's milk in phase 2, in those who have received SLIT pretreatment compared to placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy</measure>
    <time_frame>1 year</time_frame>
    <description>Efficacy defined at Double-blind, placebo-controlled food challenge (DBPCFC) as the proportion of study participants experiencing:&#xD;
No symptoms (or only mild transient symptoms) to 8 grams CM protein (approx. 250mls fresh milk) (&quot;Complete desensitisation&quot;)&#xD;
No symptoms (or only mild transient symptoms) to at least 1.4 grams CM protein (approx. 45mls fresh milk) (&quot;Partial desensitisation&quot;)&#xD;
At least a 10--fold increase in eliciting dose (defined as the lowest dose which elicits objective symptoms or signs at challenge). …at 6 and 12 months in the different treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy</measure>
    <time_frame>15 months</time_frame>
    <description>Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire:&#xD;
- Food Allergy Quality of Life Questionnaires (FAQLQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy</measure>
    <time_frame>15 months</time_frame>
    <description>Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire:&#xD;
- Food Allergy Independent Measure (FAIM)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Health-related quality of life (HRQL) from baseline - assessed using Change in EQ-5D from baseline - after each phase of immunotherapy</measure>
    <time_frame>15 months</time_frame>
    <description>Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire:&#xD;
- EQ-5D - a standardized instrument for use as a measure of health outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in self-efficacy after each phase of immunotherapy</measure>
    <time_frame>15 months</time_frame>
    <description>Change in self-efficacy at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using validated questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological outcomes</measure>
    <time_frame>12 months</time_frame>
    <description>Change in skin prick test wheal (mm), end-point titration skin prick test, allergen-specific IgE (KuA/l) between baseline and post immunotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological outcome: skin prick test</measure>
    <time_frame>12 months</time_frame>
    <description>Change in skin prick test wheal (mm) and end-point titration skin prick test between baseline and post immunotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological outcomes: Allergen-specific IgE</measure>
    <time_frame>12 months</time_frame>
    <description>Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peptide microarray</measure>
    <time_frame>12 months</time_frame>
    <description>Trend in CM-peptide binding during OIT</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Food Allergy</condition>
  <arm_group>
    <arm_group_label>SLIT followed by Conventional OIT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional OIT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed start OIT</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SLIT to cow's milk</intervention_name>
    <description>Sublingual immunotherapy</description>
    <arm_group_label>SLIT followed by Conventional OIT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low dose OIT</intervention_name>
    <description>Oral Immunotherapy (low dose)</description>
    <arm_group_label>Conventional OIT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional OIT to cow's milk</intervention_name>
    <description>Oral Immunotherapy</description>
    <arm_group_label>Conventional OIT</arm_group_label>
    <arm_group_label>Delayed start OIT</arm_group_label>
    <arm_group_label>SLIT followed by Conventional OIT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Allergic to 1.44g CM protein (approx. 40ml fresh milk) or less, at DBPCFC prior to&#xD;
             randomisation&#xD;
&#xD;
          2. Informed consent of parent/legal guardian, patient assent where possible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Required previous admission to an intensive care unit for management of an allergic&#xD;
             reaction.&#xD;
&#xD;
          2. Significant symptoms of non---IgE---mediated CM allergy within the previous 12 months.&#xD;
&#xD;
          3. Children with a past history of CM allergy currently consuming CM-containing products&#xD;
             other than extensively--heated milk in baked foods (e.g. biscuits, cakes).&#xD;
&#xD;
          4. Poorly controlled asthma within the previous 3 months (as defined by clinician&#xD;
             judgement with reference to the ICON consensus), or asthma requiring treatment with &gt;5&#xD;
             days oral corticosteroids within the previous 3 months.&#xD;
&#xD;
          5. Moderate---severe eczema, defined as requiring more than once daily application of 1%&#xD;
             hydrocortisone as maintenance treatment despite appropriate use of emollients (eczema&#xD;
             is not otherwise an exclusion criteria)&#xD;
&#xD;
          6. Clinically significant chronic illness (other than asthma, rhinitis or eczema)&#xD;
&#xD;
          7. History of symptoms of eosinophilic oesophagitis, irrespective of cause&#xD;
&#xD;
          8. Undergoing specific immunotherapy to another allergen and within the first year of&#xD;
             treatment.&#xD;
&#xD;
          9. Receiving anti--IgE therapy, oral immunosuppressants, beta---blocker or ACE inhibitor.&#xD;
&#xD;
         10. Pregnancy&#xD;
&#xD;
         11. Unwilling or unable to fulfil study requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Niño Jesús Hospital</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College London / Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>January 14, 2023</last_update_submitted>
  <last_update_submitted_qc>January 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Imperial College London</investigator_affiliation>
    <investigator_full_name>Paul Turner</investigator_full_name>
    <investigator_title>MRC Clinician Scientist, Clinical Senior Lecturer and Hon Consultant in Paediatric Allergy &amp; Immunology</investigator_title>
  </responsible_party>
  <keyword>Cow's milk allergy</keyword>
  <keyword>Desensitisation</keyword>
  <keyword>Safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Food Hypersensitivity</mesh_term>
    <mesh_term>Milk Hypersensitivity</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 11, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT02216175/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>April 24, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02216175
org study id: 18SM4569
secondary id: 18/LO/1070
nct id: NCT02216175
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Allergy to cow's milk is the most common food allergy affecting children. There is currently
      no accepted routine clinical therapy to cure milk allergy. Recently studies have attempted to
      induce desensitisation using small daily doses of cow's milk, predominantly by the oral route
      (oral immunotherapy, OIT). Although this therapy works for some people, its effects are not
      generally long lasting and it is associated with significant side effects during protocol,
      including potentially life-threatening allergic reactions.

      Pilot data suggests that sublingual immunotherapy (SLIT, where allergen is held under the
      tongue, rather than swallowed) can also induce a degree of desensitisation, but with fewer
      adverse events. However, the degree of desensitisation induced appears to be lower than that
      with oral immunotherapy.

      The investigators wish to determine whether a sublingual pretreatment phase can improve the
      safety of conventional OIT in cow's milk allergy.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Adverse events in participants
time frame: 1 year
description: Proportion of participants experiencing adverse events (excluding mild, non-transient symptoms) conventional OIT to cow's milk in phase 2, in those who have received SLIT pretreatment compared to placebo.
measure: Incidence of adverse events
time frame: 1 year
description: Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)
measure: Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy
time frame: 1 year
description: Efficacy defined at Double-blind, placebo-controlled food challenge (DBPCFC) as the proportion of study participants experiencing:
No symptoms (or only mild transient symptoms) to 8 grams CM protein (approx. 250mls fresh milk) ("Complete desensitisation")
No symptoms (or only mild transient symptoms) to at least 1.4 grams CM protein (approx. 45mls fresh milk) ("Partial desensitisation")
At least a 10--fold increase in eliciting dose (defined as the lowest dose which elicits objective symptoms or signs at challenge). …at 6 and 12 months in the different treatment groups
measure: Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy
time frame: 15 months
description: Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire:
- Food Allergy Quality of Life Questionnaires (FAQLQ)
measure: Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy
time frame: 15 months
description: Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire:
- Food Allergy Independent Measure (FAIM)
measure: Change in Health-related quality of life (HRQL) from baseline - assessed using Change in EQ-5D from baseline - after each phase of immunotherapy
time frame: 15 months
description: Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire:
- EQ-5D - a standardized instrument for use as a measure of health outcome.
measure: Change in self-efficacy after each phase of immunotherapy
time frame: 15 months
description: Change in self-efficacy at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using validated questionnaire.
measure: Immunological outcomes
time frame: 12 months
description: Change in skin prick test wheal (mm), end-point titration skin prick test, allergen-specific IgE (KuA/l) between baseline and post immunotherapy
measure: Immunological outcome: skin prick test
time frame: 12 months
description: Change in skin prick test wheal (mm) and end-point titration skin prick test between baseline and post immunotherapy
measure: Immunological outcomes: Allergen-specific IgE
time frame: 12 months
description: Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy
measure: Peptide microarray
time frame: 12 months
description: Trend in CM-peptide binding during OIT
arm group label: SLIT followed by Conventional OIT
arm group type: Experimental
description: Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk
arm group label: Conventional OIT
arm group type: Active Comparator
description: Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk
arm group label: Delayed start OIT
arm group type: Placebo Comparator
description: Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk
intervention type: Other
intervention name: SLIT to cow's milk
description: Sublingual immunotherapy
arm group label: SLIT followed by Conventional OIT
intervention type: Other
intervention name: Low dose OIT
description: Oral Immunotherapy (low dose)
arm group label: Conventional OIT
intervention type: Other
intervention name: Conventional OIT to cow's milk
description: Oral Immunotherapy
arm group label: Conventional OIT
arm group label: Delayed start OIT
arm group label: SLIT followed by Conventional OIT
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
facility: 
facility: 
country: Spain
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Imperial College London
investigator full name: Paul Turner
investigator title: MRC Clinician Scientist, Clinical Senior Lecturer and Hon Consultant in Paediatric Allergy & Immunology
mesh term: Hypersensitivity
mesh term: Food Hypersensitivity
mesh term: Milk Hypersensitivity
provided document: 
submitted: April 24, 2023