Improving the Safety of Oral Immunotherapy for Cow's Milk Allergy (SOCMA)

• Sponsor: Imperial College London
• Collaborators: JP Moulton Charitable Foundation; Sociedad Española de Alergología e Inmunología; Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica
• Information provided by (Responsible Party): Paul Turner, Imperial College London

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Food Allergy	Other: SLIT to cow's milk; Other: Low dose OIT; Other: Conventional OIT to cow's milk	Phase 2; Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	66 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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
Actual Study Start Date :	July 19, 2018
Estimated Primary Completion Date :	September 2020
Estimated Study Completion Date :	December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: SLIT followed by Conventional OIT; Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk	Other: SLIT to cow's milk; Sublingual immunotherapy; Other: Conventional OIT to cow's milk; Oral Immunotherapy
Active Comparator: Conventional OIT; Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk	Other: Low dose OIT; Oral Immunotherapy (low dose); Other: Conventional OIT to cow's milk; Oral Immunotherapy
Placebo Comparator: Delayed start OIT; Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk	Other: Conventional OIT to cow's milk; Oral Immunotherapy

Outcome Measures

Primary Outcome Measures :

1. Adverse events in participants [ Time Frame: 1 year ]
   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.

Secondary Outcome Measures :

1. Incidence of adverse events [ Time Frame: 1 year ]
   Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)
2. Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy [ Time Frame: 1 year ]

   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
3. Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy [ Time Frame: 15 months ]

   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)

4. Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy [ Time Frame: 15 months ]

   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)

5. 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 ]

   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.

6. Change in self-efficacy after each phase of immunotherapy [ Time Frame: 15 months ]
   Change in self-efficacy at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using validated questionnaire.
7. Immunological outcomes [ Time Frame: 12 months ]
   Change in skin prick test wheal (mm), end-point titration skin prick test, allergen-specific IgE (KuA/l) between baseline and post immunotherapy
8. Immunological outcome: skin prick test [ Time Frame: 12 months ]
   Change in skin prick test wheal (mm) and end-point titration skin prick test between baseline and post immunotherapy
9. Immunological outcomes: Allergen-specific IgE [ Time Frame: 12 months ]
   Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy
10. Peptide microarray [ Time Frame: 12 months ]
    Trend in CM‐peptide binding during OIT

Eligibility Criteria

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Ages Eligible for Study:	6 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Allergic to 1.44g CM protein (approx. 40ml fresh milk) or less, at DBPCFC prior to randomisation
2. Informed consent of parent/legal guardian, patient assent where possible

Exclusion Criteria:

1. Required previous admission to an intensive care unit for management of an allergic reaction.
2. Significant symptoms of non--‐IgE--‐mediated CM allergy within the previous 12 months.
3. Children with a past history of CM allergy currently consuming CM‐containing products other than extensively--heated milk in baked foods (e.g. biscuits, cakes).
4. Poorly controlled asthma within the previous 3 months (as defined by clinician judgement with reference to the ICON consensus), or asthma requiring treatment with >5 days oral corticosteroids within the previous 3 months.
5. Moderate--‐severe eczema, defined as requiring more than once daily application of 1% hydrocortisone as maintenance treatment despite appropriate use of emollients (eczema is not otherwise an exclusion criteria)
6. Clinically significant chronic illness (other than asthma, rhinitis or eczema)
7. History of symptoms of eosinophilic oesophagitis, irrespective of cause
8. Undergoing specific immunotherapy to another allergen and within the first year of treatment.
9. Receiving anti--IgE therapy, oral immunosuppressants, beta--‐blocker or ACE inhibitor.
10. Pregnancy
11. Unwilling or unable to fulfil study requirements

Contacts and Locations

Contacts

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Contact: Paul Turner	02033127754	p.turner@imperial.ac.uk
Contact: Bettina Duca, MD	02033127754	Imperial.SOCMA.study@nhs.net

Locations

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Spain
Niño Jesús Hospital	Not yet recruiting
Madrid, Spain
Contact: Pablo Rodríguez del Río, MD
United Kingdom
Imperial College London / Imperial College Healthcare NHS Trust	Recruiting
London, United Kingdom
Contact: Paul Turner, FRACP PhD p.turner@imperial.ac.uk
Sub-Investigator: Marta Vazquez, MD PhD

Sponsors and Collaborators

Imperial College London

JP Moulton Charitable Foundation

Sociedad Española de Alergología e Inmunología

Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica

More Information

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Responsible Party:	Paul Turner, MRC Clinician Scientist, Clinical Senior Lecturer and Hon Consultant in Paediatric Allergy & Immunology, Imperial College London
ClinicalTrials.gov Identifier:	NCT02216175 History of Changes
Other Study ID Numbers:	18SM4569; 18/LO/1070 ( Other Identifier: NHS Human Research Authority )
First Posted:	August 13, 2014
Last Update Posted:	July 27, 2018
Last Verified:	July 2018

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Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Paul Turner, Imperial College London:

Cow's milk allergy; Desensitisation; Safety

Additional relevant MeSH terms:

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Hypersensitivity; Food Hypersensitivity; Milk Hypersensitivity; Immune System Diseases	Hypersensitivity, Immediate; Immunologic Factors; Physiological Effects of Drugs