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

NCT01157117 | Completed Phase 2 Results DMC

• 2 other identifiers: DAIT AADCRC-MSSM-01U19AI044236
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 3

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.

Conditions

Milk Allergy

Keywords

food allergy

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Clinical Tolerance to Milk

  Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of milk protein during a double-blind placebo-controlled oral food challenge were then given an open feeding of milk and those who successfully consumed the open feeding were counted as successes.

  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 (13)

• Incidence of Dosing Reactions to Milk OIT During the Escalation Phase

  Baseline to completion of Escalation Phase at 22 to 40 weeks

• Incidence of Dosing Reactions to Milk OIT During the Maintenance Phase

  After completion of Escalation Phase at 22 to 40 weeks, the Maintenance Phase lasted up to Month 30

• Incidence of Severe Hypersensitivity Reactions to Milk OIT

  Through completion of milk OIT dosing (at Month 28 if failed desensitization OFC, at Month 30 if passed desensitization OFC)

• Maximum Tolerated Dose of Milk Oral Immunotherapy (OIT)

  Baseline to completion of Escalation Phase at 22 to 40 weeks

• Percentage of Participants in the Xolair® (Omalizumab) Group vs. Placebo Group Developing Desensitization to Milk

  Month 28

Study Arms (3)

Omalizumab/milk OIT

EXPERIMENTAL

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.

Biological: Omalizumab; Drug: Milk powder

Placebo for omalizumab/milk OIT

PLACEBO COMPARATOR

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.

Biological: Placebo for omalizumab; Drug: Milk powder

Untreated control

NO INTERVENTION

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.

Interventions

Placebo for omalizumab BIOLOGICAL

Placebo for omalizumab is injected subcutaneously every 2-4 weeks for 16 months at a volume designed to match that of the verum treatment group (determined by the participant's IgE level and weight).

Also known as: Placebo for Xolair

Placebo for omalizumab/milk OIT

Omalizumab BIOLOGICAL

Omalizumab is injected subcutaneously every 2-4 weeks for 28 months at a dose determined by the participants IgE level and weight.

Also known as: Xolair

Omalizumab/milk OIT

Milk powder DRUG

Milk powder is ingested orally at a dosage of up to 3.84 grams of of milk protein daily from Month 4 through Month 28 if the Month 28 10 g milk OFC is failed, and through Month 30 if the Month 28 10 g milk OFC is passed.

Omalizumab/milk OIT; Placebo for omalizumab/milk OIT

Eligibility Criteria

• Age: 7 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Hugh A Sampson, MD: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (3)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (2)

• 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.

  PMID: 26581915 RESULT

• 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.

  PMID: 25609353 DERIVED

MeSH Terms

Conditions

Milk Hypersensitivity; Food Hypersensitivity

Interventions

Omalizumab; Refit milk powder

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Hugh A. Sampson
• Organization: Ichan School of Medicine at Mount Sinai

hugh.sampson@mssm.edu

212-659-9426

Study Officials

• Hugh A. Sampson, M.D.

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dean for Translational Biomedical Sciences, Director, Jaffe Food Allergy Institute

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 5, 2010
• Study Start: August 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: October 1, 2015
• Last Updated: August 14, 2020
• Results First Posted: April 6, 2016

Record last verified: 2020-08

Locations

US (3)