Asthma in Children, Food; Allergy, Anaphylactic Shock
Conditions
Brief summary
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.
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
Interventions
BIOLOGICALOmalizumab
Administration of Omalizumab at the doses indicated for asthma in the EMA information leaflet.
Sponsors
Bambino Gesù Hospital and Research Institute
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Milligram tolerated food allergen (gms) of raw and baked milk, raw and baked egg, hazelnut, peanut, wheat, and/or fish at T1. | Four months (T1) | Threshold of reactivity assessed as No Observed Adverse Events Level (NOAEL) to each of the analysed food |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NOAEL for raw and baked milk, raw and baked egg, hazelnut, peanut, wheat, and/or fish at T2. | Eight months (T2) | Change in the NOAEL at the third OFC to the foods who did not pass the OFC at T1 |
| NOAEL for raw and baked milk, raw and baked egg, hazelnut, peanut, wheat, and/or fish at T3. | Twelve months (T3) | Change in the NOAEL at the fourth OFC to the foods who did not pass the OFC at T2 |
| Change in number of anaphylactic events | Twelve months (T3) | Number of episodes of anaphylaxis in the 6 - 12 months preceding T0 compared with those 6 - 12 months after the first dose of Omalizumab |
| Rate of severity of anaphylactic events | Twelve months (T3) | 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. |
| Proportion of negative OFCs at T1 | Four months (T1) | Percentage of OFC tolerated until the last dose of food. |
| Quality of Life score | Four (T1), eight (T2), twelve (T3) months | Change from baseline in age-appropriate FA-QoL score: 0, better; 84, worse outcome |
| Total IgE | Four (T1), eight (T2), twelve (T3) months | Change from baseline in total IgE |
| Specific IgE for milk, egg, hazelnut, peanut, wheat, and/or fish | Four (T1), eight (T2), twelve (T3) months | Change from baseline in sIgE; |
| Asthma Control Test (ACT) | Twelve months (T3) | Change from baseline in ACT score: 5 worse, 25 better outcome |
Countries
Italy
Outcome results
None listed