Clinical trial NCT01157117: OIT and Xolair® (Omalizumab) in Cow's Milk Allergy
Official title: Oral Immunotherapy Combined With Humanized Monoclonal Anti-IgE Antibody Xolair® (Omalizumab)in the Treatment of Cow's Milk Allergy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Milk Allergy
Keywords: food allergy
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2010-07-05
Enrollment: 77
Sex: ALL
Minimum age (years): 7
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Food allergy affects up to 4% of the U.S. population and is most common in young children. Milk allergy is the most common cause of food allergy in infants and young children, and usually develops in the first year of life. There is no treatment for food allergy and the current standard of care for milk-allergic individuals is the avoidance of milk-containing products. Research is underway to identify potential therapeutic strategies to reduce or eliminate the adverse effects experienced by milk-allergic individuals when they consume milk-containing products.

Several studies have suggested that milk-allergic children who receive milk protein oral immunotherapy (OIT) may become desensitized to milk, resulting in short term protection against accidental ingestion of milk products. However, these children did not develop "tolerance," which is long term protection even after milk immunotherapy is stopped. A potential strategy to induce tolerance to milk uses milk in combination with Xolair® (omalizumab). Xolair consists of anti-IgE molecules that attach to IgE, the major antibody involved in allergic reactions. The goal of this clinical trial is to see whether Xolair® in combination with milk protein OIT is safer and more effective than OIT alone in inducing tolerance to milk and milk products. Participants will be administered a double blind, placebo controlled milk challenge at various time points in the study. If desensitization is achieved participants will be tested for tolerance at a certain time point after stopping treatment.


Eligibility criteria: Inclusion Criteria:

* Subject and/or parent/ legal guardian must be able to understand and provide written informed consent
* Written or verbal assent from all study subjects less than 18 years (per site Institutional Review Board (IRB) regulations)
* 7 to 35 years of age; any gender; any racial and ethnic origin
* No known contraindications to therapy using oral immunotherapy with milk protein or Xolair® (omalizumab)
* All female subjects of childbearing potential must have a negative pregnancy test upon study entry
* All treated females of childbearing potential must agree to use FDA approved methods of birth control for the duration of the study

Active Treatment Subjects:

* Cow's milk allergy confirmed by a positive double-blind placebo controlled milk challenge (DBPCMC) to a dose of less than 2 g of milk protein within the past 6 months
* A skin prick test positive to milk (diameter of wheal \>= 3.0 mm) OR detectable serum milk specific Immunoglobulin E (IgE) level within the previous 12 months (UniCAP \> = 0.35 kUA/L (allergen-equivalent kilounits per liter))

Control Subjects:

• A skin prick test positive to milk (diameter of wheal \>= 10.0 mm) OR detectable serum milk specific IgE level within the previous 12 months (UniCAP \>= 15 kUA/L)

Exclusion Criteria:

* A history of life-threatening anaphylaxis to milk (involving hypotension or requiring mechanical ventilation)
* Known allergy to any components of the placebo for Xolair®
* Chronic disease other than asthma, atopic dermatitis, or allergic rhinitis requiring therapy (e.g., heart disease, diabetes)
* Use of β-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB), or calcium channel blockers
* Severe asthma
* Mild or moderate asthma with any of the following criteria met:

  * Forced expiratory volume in the first second (FEV1) \< 80% with or without controller medications
  * Inhaled corticosteroids (ICS) dosing of \>500 mcg daily fluticasone (or equivalent inhaled corticosteroids based on NHLBI dosing chart)
  * history of daily oral steroid dosing for \>1 month during the past year
  * burst oral steroid course in the past 6 months
  * more than one burst oral steroid course in the past year
  * more than one hospitalization in the past year for asthma, or
  * more than one ER visit in the past 6 months for asthma
* Baseline spirometry (or peak flow rate (PFR) if unable to perform spirometry) result of FEV1\<80%
* Pregnancy or lactation. All females of child-bearing age will undergo pregnancy testing. All treated females will confirm compliance to appropriate birth control measures throughout the course of the study;
* Participation in any interventional study for the treatment of food allergy in the past 6 months
* Subject is on a buildup phase of standard subcutaneous immunotherapy for inhalant allergens (may be enrolled on maintenance dose);
* Use of Xolair® (omalizumab) or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual immunotherapy) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year
* Inability to discontinue antihistamines for 5 half-lives prior to routine study tests (DBPCMC or endpoint titration tests)
* Known sensitivity to Xolair® (omalizumab) or to the class of study drugs
* Baseline serum total IgE over 1,300 IU/mL or body weight more than 150 kg, or subjects with weight-IgE combination that yields a dose requirement greater than 750 mg (due to limitations of Xolair® (omalizumab) dosing)
* Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements
* Inability or unwillingness of a subject to give written informed consent or comply with study protocol
* Use of investigational drugs within 90 days of participation
* Other contraindications to milk oral immunotherapy or Xolair® (omalizumab)
* Recipient of any licensed or investigational live attenuated vaccine(s) within 2 months of enrollment
* Families who do not speak English
* Systemic steroids oral, intramuscular (IM), or IV for indications other than asthma for greater than 3 weeks in the past 6 months

Primary outcomes:
measure: Percentage of Subjects in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Clinical Tolerance to Milk
timeFrame: Month 32 which is 8 weeks following the discontinuation of milk OIT for both groups and 4 months after discontinuation of omalizumab for the omalizumab group
Secondary outcomes:
measure: Incidence of Dosing Reactions to Milk OIT During the Escalation Phase
timeFrame: Baseline to completion of Escalation Phase at 22 to 40 weeks
measure: Incidence of Dosing Reactions to Milk OIT During the Maintenance Phase
timeFrame: After completion of Escalation Phase at 22 to 40 weeks, the Maintenance Phase lasted up to Month 30
measure: Incidence of Severe Hypersensitivity Reactions to Milk OIT
timeFrame: Through completion of milk OIT dosing (at Month 28 if failed desensitization OFC, at Month 30 if passed desensitization OFC)
measure: Maximum Tolerated Dose of Milk Oral Immunotherapy (OIT)
timeFrame: Baseline to completion of Escalation Phase at 22 to 40 weeks
measure: Percentage of Participants in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Desensitization to Milk
timeFrame: Month 28
measure: Time to Maximum Tolerated Dose
timeFrame: Baseline to completion of Escalation Phase at 22 to 40 weeks
measure: Change From Baseline to Month 32 in Area Under the Curve for Milk Endpoint Titration Prick Skin Test
timeFrame: Month 32
measure: Change From Baseline to Month 32 in Antigen-specific Immunoglobulin E (IgE)
timeFrame: Month 32
measure: Change From Baseline to Month 32 in Antigen-specific Immunoglobulin G4 (IgG4)
timeFrame: Month 32
measure: Change From Baseline to Month 38 in Antigen-specific Immunoglobulin E (IgE)
timeFrame: Month 38
measure: Change From Baseline to Month 38 in Antigen-specific Immunoglobulin G4 (IgG4)
timeFrame: Month 38
measure: Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 32 in Basophils Stimulated by Milk
timeFrame: Month 32
measure: Change in Percent of Cells Positive for Cluster of Differentiation 63 (CD63) at Month 38 in Basophils Stimulated by Milk
timeFrame: Month 38
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Hugh A. Sampson, M.D.
role: STUDY_CHAIR
References:
citation: Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, Plaut M, Sampson HA. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J Allergy Clin Immunol. 2016 Apr;137(4):1103-1110.e11. doi: 10.1016/j.jaci.2015.10.005. Epub 2015 Nov 12.
citation: Noone S, Ross J, Sampson HA, Wang J. Epinephrine use in positive oral food challenges performed as a screening test for food allergy therapy trials. J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):424-8. doi: 10.1016/j.jaip.2014.10.008. Epub 2015 Jan 13.