Study analyzing the efficacy and safety of low-dose oral immunotherapy in children with severe allergy to cow's milk treated with Omalizumab. ILO study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Infantil Universitario Nino Jesus

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2023-09-15

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hospital Infantil Universitario Niño Jesús

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To analyze the safety and efficacy of a combined treatment of oral immunotherapy with low doses of milk and Omalizumab in patients with severe cow's milk allergy after reducing the dose of Omalizumab.

Secondary objectives 1

1. • To analyze the safety and efficacy of the escalation phase of an oral immunotherapy with low doses of milk during treatment with Omalizumab. • Analyze the changes in the size of the skin test and the levels of specific serum IgE and IgG4 against cow's milk and its proteins. • To study the relationship between clinical responses to oral milk immunotherapy and skin test size and specific serum IgE and IgG4 levels. • Detect individual predictors of maintenance of dose tolerance of oral milk immunotherapy after reducing the dose of Omalizumab. • To analyze changes in the quality of life of patients with severe milk allergy who receive combined therapy Milk oral immunotherapy - Omalizumab.

Conditions and MedDRA coding

Severe IgE-mediated cow's milk allergy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Men and women between the ages of 6 and 15 at the time of signing the consent/assent. 2. Signature of informed consent and/or assent (where applicable), which must be obtained prior to participation in the study. Parents/legal guardians and participants ages 12-15 must be able to understand and provide written consent and assent, respectively. 3. Documented medical history of allergy to milk or foods containing milk. 4. Episodes of anaphylaxis due to ingestion of cow's milk (> 0) and/or the diagnosis of asthma. 5. Serum IgE to cow's milk and casein > 49 kUA/L at Screening Visit 1. 6. Positive skin tests for cow's milk and casein. It is defined as a mean wheal diameter (mean of the sum of the largest and smallest diameters) > 3 mm compared to the negative control. 7. Participants must weigh > 19 kg at Screening Visit 1. 8. Participants must be able to receive injections (study drug), perform oral challenge testing, and must continue to be exposed to cow's milk throughout the study.

Exclusion criteria 1

1. 1. Use of other investigational drugs within 5 half-lives or 30 days prior to Screening Visit 1 (whichever is longer). 2. History of allergy to omalizumab or its excipients. 3. Allergy to any of the components of the matrix used for the double-blind placebo-controlled oral challenge trial (PODCCP) with milk. 4. Inability to complete study procedures and follow-up. 5. Subjects having a combination of weight and IgE that requires Omalizumab doses greater than 1,200 mg/4 weeks. 6. History of life-threatening allergic reaction after ingestion of milk that required admission to the Intensive Care Unit in the 60 days prior to the Screening Visit. 7. Participants with uncontrolled asthma (according to GINA, GINA 2022 guidelines) who meet any of the following criteria: a. FEV1 < 80% predicted at Screening Visit 1. b. One hospitalization for asthma in the 12 months prior to Screening Visit 1. 8. Patients with severe persistent asthma who require continued treatment with omalizumab. 9. History of eosinophilic esophagitis, other eosinophilic gastrointestinal disease, symptoms of dysphagia (eg, difficulty swallowing), recurrent gastrointestinal symptoms of undiagnosed etiology, or meeting clinical criteria for cow's milk protein-induced enterocolitis (FPIES) . 10. Current or past history of mast cell disorders, including mastocytosis. 11. Use of prohibited medication or medication not permitted under certain conditions. 12. Participants with evidence of parasitic helminthic infestation to a pathogenic organism evidenced by stool study at Screening Visit 1. 13. History of malignancy in the previous 5 years. 14. Clinically significant cardiovascular diseases. 15. Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or calcium channel blockers. 16. Neurological, psychiatric or metabolic diseases that may interfere or compromise the safety of patients or the evaluation, interpretation of study results or prevent completion of the study. 17. History of, or current treatment for, liver disease or serum transaminase levels 1.5 times the upper limit of normal at Screening Visit 1. 18. History of renal disease or serum creatinine levels 1.5 times the upper limit of normal at Screening Visit 1. 19. Platelets < 100,000/µL at Screening Visit 1. 20. Current participation in any other intervention study. 21. Subject is in dose escalation (dose escalation) phase of immunotherapy for another allergen (has not reached maintenance dose). 22. Pregnancy or lactation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects tolerating 300 mg cow's milk protein with no symptoms or only Grade 1 symptoms (oFASS-5) in the double-blind placebo-controlled oral cow's milk challenge trial (DBPCOC) without Omalizumab (without-Oz).

Secondary endpoints 1

1. • Proportion of subjects tolerating the 300 mg dose of cow's milk protein with no or only Grade 1 symptoms (oFASS-5) in the double-blind placebo-controlled oral cow's milk challenge test (DBPCOC) at 4 months from initiation Omalizumab (Oz1). • Proportion of subjects tolerating >300 mg cow's milk protein with no or only Grade 1 symptoms (oFASS-5) in the open cow's milk oral challenge test (Oz1-a).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Infantil Universitario Nino Jesus

Sponsor organisation

Hospital Infantil Universitario Nino Jesus

Address

Avenida Menendez Pelayo 65

City

Madrid

Postcode

28009

Country

Spain

Scientific contact point

Organisation

Hospital Infantil Universitario Nino Jesus

Contact name

Carmelo Escudero

Public contact point

Organisation

Hospital Infantil Universitario Nino Jesus

Contact name

Carmelo Escudero

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications