Clinical trial NCT04045301: Omalizumab to Accelerate a Symptom-driven Multi-food OIT
Official title: A 15 Months, Double-Blind, Randomized Controlled Trial Comparing 20 Weeks of Two Dosages of Omalizumab to Placebo to Accelerate a Symptom-driven Oral Immunotherapy Schedule in Subjects Aged 6 to 25 Years With Multiple Food Allergies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Food IgE-mediated Allergy
Immunotherapy
Omalizumab
Physiological Effects of Drugs
Keywords: multi-food OIT
oral immunotherapy
omalizumab
symptom-driven protocol
double-Blind, randomized controlled trial
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: The Hospital for Sick Children
name: Centre hospitalier de l'Université de Montréal (CHUM)
name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
First posted: 2019-08-05
Enrollment: 90
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine the dose-related efficacy of a 20-week treatment of omalizumab started 8 weeks before the onset of a symptom-driven multi-food oral immunotherapy (OIT) protocol at decreasing time to OIT maintenance dose. Two dosages of omalizumab will be compared to placebo during an oral immunotherapy protocol for three simultaneous food allergens.

Detailed description: This is a phase 2b, multi-center randomized controlled trial comparing 2 doses of omalizumab to placebo in subjects 6 to 25 years old with multiple food allergies undergoing a symptom-driven multi-food OIT protocol.

Subjects will undergo a screening period involving a DBPCFC to a mix of three allergens which will determine their eligibility and eliciting dose.

Eligible subjects will be randomized to one of 2 omalizumab dosages or placebo at a ratio of 2:2:1 for a total period of 20 weeks.

They will undergo initial food escalation (IFE) to determine their starting food treatment mix dose for three simultaneous food allergens after a pre-treatment period of 8 weeks with the study drug.

Subjects will undergo up-dosing OIT visits at the clinic every two weeks, until a maintenance dose of 1500mg of protein (500mg per food) is reached (primary endpoint).

Eligibility criteria: Inclusion criteria:

1. Male or female subjects 6 to 25 years old at screening visit.
2. History of IgE-mediated allergy to at least three foods within the following list: peanut, milk, egg, wheat, oat, soy, barley, rye, buckwheat, hazelnut, pecan, cashew, pistachio, almond, walnut and sesame.
3. Subjects currently following a strict avoidance of these three foods.
4. Positive SPT with a largest wheal diameter ≥ 6 mm to all three foods.
5. Food-specific IgE level greater than 15 kU/L for all three foods
6. Positive DBPCFC to treatment food mix with an eliciting dose ≤ 300 mg of total food protein.
7. Signed informed consent and assent.

Exclusion criteria

1. Subjects reacting objectively to the placebo during the screening DBPCFC.
2. Severe asthma as defined by GINA 201948.
3. Active or past confirmed eosinophilic oesophagitis.
4. Subject currently under allergen immunotherapy.
5. Subject/parent with excessive anxiety unlikely to cope with study conditions as per investigator's opinion.
6. Subject/parent unwillingness to comply with study requirements.
7. Subject unwillingness to ingest a daily food dose of up to 1500 mg of allergen protein.
8. Inability to discontinue anti-histamine medication prior to study procedures.
9. Known allergy to omalizumab or its excipients.
10. Known allergy to components of the placebo food treatment mix that cannot be substituted without interfering with the blind (e.g.: dates, banana, chocolate syrup)
11. Use of immunosuppression or immunomodulatory drug (including omalizumab) or food oral immunotherapy or investigational treatment or procedure within 1 year.
12. Relative contraindication or inability to use epinephrine auto-injector.
13. Subjects receiving beta-blockers or angiotensin converting-enzyme (ACE) inhibitors.
14. Pregnancy or lactation for the duration of the study.
15. Any condition that is not compatible with the study treatment or procedures as per investigator judgment.

Primary outcomes:
measure: To determine the efficacy of omalizumab at decreasing time-to-maintenance during a symptom-driven multi-food OIT protocol.
timeFrame: Assessed up to 52 weeks after IFE
Secondary outcomes:
measure: Change in reactivity threshold to food treatment mix after pre-treatment with study drug.
timeFrame: Measured 8 weeks after starting investigational product
measure: Average up-dosing speed while on study drug.
timeFrame: From week 0 to week 12 post IFE
measure: Mean cumulative function of allergic adverse events attributable to food dosing throughout the trial.
timeFrame: For one year following IFE
measure: Rate of treatment failure
timeFrame: At any time during the 12-month OIT phase
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - Centre Hospitalier Universitaire de Sherbrooke (CHUS)
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Philippe Bégin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langlois A, Lavergne MH, Leroux H, Killer K, Azzano P, Paradis L, Samaan K, Lacombe-Barrios J, Masse B, Des Roches A, Begin P. Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy. Allergy Asthma Clin Immunol. 2020 Apr 17;16:25. doi: 10.1186/s13223-020-00419-z. eCollection 2020.