OIT and Xolair® (Omalizumab) in Cow's Milk Allergy

Hugh A Sampson, MD

Status and phase: Completed; Phase 2

Conditions: Milk Allergy

Treatments: Biological: Omalizumab; Biological: Placebo for omalizumab; Drug: Milk powder

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01157117

U19AI044236 (U.S. NIH Grant/Contract)

DAIT AADCRC-MSSM-01

Details and patient eligibility

About

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.

Enrollment: 77 patients

Sex: All

Ages: 7 to 35 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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77 participants in 3 patient groups, including a placebo group

Omalizumab/milk OIT

Experimental group

Description:

Participants receive blinded omalizumab injections every 2 to 4 weeks through Month 16 and unblinded omalizumab injections thereafter until the Month 28 desensitization oral food challenge (OFC). Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28, participants complete a 10g milk OFC and discontinue omalizumab injections. If they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.

Treatment:

Biological: Omalizumab

Drug: Milk powder

Placebo for omalizumab/milk OIT

Placebo Comparator group

Description:

Participants receive blinded placebo for omalizumab injections every 2 to 4 weeks through Month 16; after unblinding the injections are discontinued. Participants ingest milk powder daily starting at Month 4 with a dose of 0.07 mg milk protein and escalate for 22 to 40 weeks until reaching the maintenance dose of 3.84 g milk protein (minimum required maintenance dose is 520 mg milk protein). At Month 28, participants complete a 10g milk oral food challenge (OFC); if they fail the OFC they permanently discontinue ingestion of the milk powder; if they pass the OFC they continue ingestion of the maintenance dose of milk powder through Month 30 and then discontinue it.

Treatment:

Biological: Placebo for omalizumab

Drug: Milk powder

Untreated control

No Intervention group

Description:

Participants did not receive any study intervention but provided regular blood draws at specific study time points to allow mechanistic comparisons with the participants in the other two groups who did receive study intervention.