Omalizumab in Severe Asthmatics With Food Allergy (OSAFA)

Effects of Omalizumab on Food Allergy in Children With Severe Asthma: A Real Life Study

A prospective assessment of the impact of Omalizumab in terms of efficacy, safety, and quality of life (FA-QoL) in patients with moderate/severe asthma and history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat. Evaluation of the trend of total and specific IgE during Omalizumab treatment.

Study Overview

• Status: Completed
• Conditions: Asthma in Children; Food; Allergy, Anaphylactic Shock
• Intervention / Treatment: Biological: Omalizumab

Detailed Description

Children (6-18 yrs) with severe asthma eligible for treatment with Omalizumab and reporting food anaphylaxis to be assessed for their concomitant food allergy.

At T0:

• oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s);
• number and severity of food-allergic reactions in the previous 12 months recorded
• Asthma Control Test
• Food Allergy-Quality of Life (FA-QoL) questionnaire
• total IgE
• specific IgE for the culprit foods

At T1 - four months after starting Omalizumab treatment:

• OFCs to the previously positive foods with evaluation of the threshold of reaction
• number and severity of food-allergic reactions in the previous 4 months recorded
• Asthma Control Test
• Food Allergy-Quality of Life (FA-QoL) questionnaire
• total IgE
• specific IgE for the culprit foods

At T2 - eight months after starting Omalizumab treatment:

• OFCs to the previously positive foods with evaluation of the threshold of reaction
• number and severity of food-allergic reactions in the previous 4 months recorded
• Asthma Control Test
• Food Allergy-Quality of Life (FA-QoL) questionnaire
• total IgE
• specific IgE for the culprit foods

At T1 - twelve months after starting Omalizumab treatment:

• OFCs to the previously positive foods with evaluation of the threshold of reaction
• number and severity of food-allergic reactions in the previous 4 months recorded
• Asthma Control Test
• Food Allergy-Quality of Life (FA-QoL) questionnaire
• total IgE
• specific IgE for the culprit foods

• Study Type: Observational
• Enrollment (Actual): 65

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00145
    • Pediatric Hospital Bambino Gesù IRCCS - Allergy Dpt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

• Children with severe asthma eligible for treatment with Omalizumab consecutively enrolled at the Bambino Gesu Pediatrica Hospital IRCCS in Rome
• ACT < 20
• Food allergy as described
• History of food-induced anaphylaxis
• positive OFCs with milk, baked milk, egg, baked egg, wheat, peanut, hazelnut, codfish.

Description

Inclusion Criteria:

• Age 6 - 18 years
• Severe persistent allergic asthma according to the GINA guidelines
• Sensitized to a perennial aeroallergen, as witnessed by positive skin test and/or in vitro reactivity
• Symptoms inadequately controlled with inhaled corticosteroids + another medication, as witnessed by an ACT ≤ 19
• On treatment with high dose inhaled corticosteroids + another medication. Threshold dose for inhaled corticosteroids set at 400 mcg/day budesonide (or equivalent doses) for children < 12 years, at 800 mcg/day for older patients.
• Immediate food allergy with anaphylactic symptoms within 1hr. of ingestion of milk, egg, wheat, peanut, hazelnut, and/or codfish.
• Total IgE < 70 and >1,500 kU/L at baseline
• Sensitivity to food allergen documented by a positive skin prick test result and/or allergen-specific IgE level, with 0.35 kU/L as a lower limit of eligibility
• Positive OFC within the past 12 months, with minimal or no reactions to the placebo challenge.
• Trained on the proper use of epinephrine
• In case of female subjects of child-bearing potential, negative human chorionic gonadotropin blood sample for pregnancy testing
• No known contraindications to oral immunotherapy with food protein or Omalizumab
• Parent/legal guardian written informed consent

Exclusion Criteria:

• Total IgE at screening > 70 or ≤ 2,500 kUI/L
• allergy to food(s) not investigated in this study
• Immune deficiency
• Previous reaction to Omalizumab
• Previous organ transplantation
• Use of monoclonal antibodies in the previous 6 months
• Subjects with gastrointestinal or gastroesophageal disease, chronic infections, scleroderma, hepatic and gallbladder disease, chronic non-allergic pulmonary disease.
• Subjects who have received an experimental drug in the last 30 days prior to admission into this study or who plan to use an experimental drug during the study
• Pregnant or breast-feeding females.
• Subjects with food protein induced enterocolitis syndrome (FPIES)
• Subjects is on a build-up phase of standard subcutaneous immunotherapy for inhalant allergens (may be enrolled on maintenance dose)
• Inability to discontinue antihistamines for 5 half-lives prior to routine study tests (OFC)
• Subjects with weight-IgE combination yielding a dose requirement greater than 600 mg according to the EMA schedule for Omalizumab
• Systemic steroids oral, IM, or IV for indications other than asthma for more than 3 weeks in the past 6 months.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe asthmatics with history of food anaphylaxis; Omalizumab will be administered i.m. with doses ranging from 150 mg every 28 days to 600 mg every 14 days, according to EMA dosing range table.	Biological: Omalizumab; Administration of Omalizumab at the doses indicated for asthma in the EMA information leaflet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Milligram tolerated food allergen (gms) of raw and baked milk, raw and baked egg, hazelnut, peanut, wheat, and/or fish at T1.	Threshold of reactivity assessed as No Observed Adverse Events Level (NOAEL) to each of the analysed food	Four months (T1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of negative OFCs at T1	Percentage of OFC tolerated until the last dose of food.	Four months (T1)
NOAEL for raw and baked milk, raw and baked egg, hazelnut, peanut, wheat, and/or fish at T2.	Change in the NOAEL at the third OFC to the foods who did not pass the OFC at T1	Eight months (T2)
NOAEL for raw and baked milk, raw and baked egg, hazelnut, peanut, wheat, and/or fish at T3.	Change in the NOAEL at the fourth OFC to the foods who did not pass the OFC at T2	Twelve months (T3)
Change in number of anaphylactic events	Number of episodes of anaphylaxis in the 6 - 12 months preceding T0 compared with those 6 - 12 months after the first dose of Omalizumab	Twelve months (T3)
Rate of severity of anaphylactic events	Severity of episodes of anaphylaxis in the 6 - 12 months preceding T0 compared with those 6 - 12 months after the first dose of Omalizumab; PRACTALL score: 1 - mild, 2 - moderate, 3 - severe.	Twelve months (T3)
Asthma Control Test (ACT)	Change from baseline in ACT score: 5 worse, 25 better outcome	Twelve months (T3)
Quality of Life score	Change from baseline in age-appropriate FA-QoL score: 0, better; 84, worse outcome	Four (T1), eight (T2), twelve (T3) months
Total IgE	Change from baseline in total IgE	Four (T1), eight (T2), twelve (T3) months
Specific IgE for milk, egg, hazelnut, peanut, wheat, and/or fish	Change from baseline in sIgE;	Four (T1), eight (T2), twelve (T3) months

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute

Publications and helpful links

General Publications

• Fiocchi A, Artesani MC, Riccardi C, Mennini M, Pecora V, Fierro V, Calandrelli V, Dahdah L, Valluzzi RL. Impact of Omalizumab on Food Allergy in Patients Treated for Asthma: A Real-Life Study. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1901-1909.e5. doi: 10.1016/j.jaip.2019.01.023. Epub 2019 Feb 20.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Food Hypersensitivity; Anaphylaxis; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: 1501/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual Participating Data will be made available to researchers upon reasonable request.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact alexfioc@gmail.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes