Omalizumab in the Treatment of Peanut Allergy

Food Allergy Clinical Trial

Official title:

Effects of Omalizumab on Peanut Allergen Induced Cellular and Clinical Responses in Peanut Allergic Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00949078
• Other study ID #: AADCRC-JHU-02
• Secondary ID: 1U19AI070345
• Status: Completed
• Phase: Phase 2
• First received: July 29, 2009
• Last updated: March 28, 2016
• Start date: July 2009
• Est. completion date: August 2011

Study information

• Verified date: March 2016
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if treatment with omalizumab (Xolair, anti-IgE) can eliminate or reduce symptoms of peanut allergy.

Description:

The study will evaluate if omalizumab is an effective treatment for peanut allergy. In addition we will further evaluate the role of allergic cells (mast cells and basophils) and IgE in food allergy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Male or Female (non-pregnant), age 18-50

• Females must be: Surgically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation), OR postmenopausal (at least 1 year since last menses), OR using one of the following medically acceptable forms of birth control throughout the duration of the study:

• Systemic contraceptives

• Diaphragm with intravaginal spermicide

• Cervical cap

• Intrauterine device

• Condom with intravaginal spermicide Females in certain categories (not sexually active, vasectomized partner) will be admitted at the discretion of the investigator on a case-by-case basis.

Females, excluding those more than 1 year postmenopausal or who are surgically sterile, must have a negative urine pregnancy test at Visit 1 and other visits specified in this protocol. If a subject becomes pregnant during the study participation, they will be discharged from the study and followed for any adverse events until termination of the pregnancy or delivery is complete. Given that the drug is in pregnancy category B, we will follow the pregnant mother for any adverse events for the duration of the study.

• Physician diagnosed peanut allergy OR convincing clinical history of peanut allergy with its onset in early childhood.

• Positive puncture skin test to peanut greater than or equal to 3 mm diluent control

• Positive ImmunoCAP to peanut =0.35 kU/L.

• In vitro basophil responsiveness to peanut allergen, with greater than 20% histamine release or 10-19% if greater than 50% of an optimal anti-IgE response (at baseline visit).

• Subjects must have a positive oral food challenge to peanut as defined by having objective signs of a clear allergic reaction at a cumulative dose of peanut protein <1000 mg. Objective allergic signs may include oral urticaria, cutaneous urticaria, rhinorrhea, sneezing, coughing, wheezing, or vomiting.

Exclusion Criteria:

• Asthma with FEV1 < 80% predicted or severe persistent asthma per NAEP Standards (2007 National Asthma Education and Prevention Program Expert Panel Report III guidelines) or poorly controlled asthma with oral corticosteroid use for exacerbation in last 6 months.

• History of severe allergic reaction to peanut requiring intubation or ICU admission.

• Late onset peanut allergy, defined as subjects who had previously tolerated peanut on a regular basis before their initial reaction.

• Patients with biopsy proven eosinophilic enteropathy will be excluded.

• Patients with total serum IgE levels less than 30 IU/mL or greater than 700 IU/mL at the time of enrollment will be excluded.

• Patients with hematocrit < 32%, WBC count <4000/microliter, platelet < 75000/microliter, creatinine > 141.4 micromolar/L, or AST > 100 IU/L will be excluded if these abnormalities are present at the time of enrollment.

• Body weight less than 30 kg or greater than 150 kg at enrollment will be excluded.

• Patients with plans to become pregnant or breastfeed will be excluded from the study. Patients must indicate they will use methods to avoid pregnancy.

• Other significant medical conditions (e.g., liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders), which, in the opinion of the Investigator, make the subject unsuitable for induction of food reactions.

• Current or prior use of omalizumab in the past 12 months.

• Use of non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator (not including corticosteroids) or biologic therapy within the past year.

• Use of beta-blockers (oral or ocular), angiotensin-converting enzyme (ACE) inhibitors, or angiotensin-receptor blockers (ARB) within 72 hours prior to either of the qualification OFC.

• Use of antihistamines (within 3 days for short acting and 5 days for long acting) prior to the screening OFC.

• Use of antihistamines (within 3 days for short acting and 5 days for long acting) prior to the study OFC. These procedures should be rescheduled when off antihistamines for the required time.

• Inability to discontinue antihistamines for routine study tests.

• History of ischemic cardiovascular disease (i.e., previous MI, angina etc) or uncontrolled hypertension.

• Significant upper respiratory tract infection (URI) within 7 days of any OFC; OFCs should be rescheduled within 7 days following resolution of URI.

• Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.

• Use of any investigational drugs within 8 weeks of participation.

• Any contraindication to omalizumab including patients with a previous hypersensitivity to omalizumab.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Food Allergy
• Food Hypersensitivity
• Hypersensitivity
• Peanut Allergy
• Peanut Hypersensitivity

Intervention

Drug:
• omalizumab
omalizumab subcutaneously every 2-4 weeks depending on participant weight and total IgE

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Leung DY, Sampson HA, Yunginger JW, Burks AW Jr, Schneider LC, Wortel CH, Davis FM, Hyun JD, Shanahan WR Jr; Avon Longitudinal Study of Parents and Children Study Team. Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med. 2003 Mar 13;348(11):986-93. Epub 2003 Mar 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants who have a four-fold increase in the dose of peanut protein needed to induce positive challenge (with final threshold dose >1000 mg) at the 6 month oral food challenge		6 months	No
Secondary	Reduction of peanut-allergen induced basophil histamine release in vitro in subjects treated with omalizumab		6 months	No
Secondary	Changes in dose of peanut protein needed to induce a positive challenge at the second oral food challenge compared to baseline		1-2 months	No
Secondary	Changes in skin test reactivity on omalizumab therapy and up to 6 months during drug withdrawal.		12 months	No
Secondary	Changes in free and total peanut-specific IgE and total IgE as well as the ratio of peanut-specific IgE to total IgE on omalizumab therapy and up to 6 months after drug withdrawal		12	No
Secondary	Changes in basophil markers CD203c, CD63, CD69/ST2, and basogranulin, as well as tryptase during oral food challenges on omalizumab therapy		6 months	No
Secondary	Changes in the indirect effects of serum on basophil histamine release on omalizumab therapy and up to 6 months after drug withdrawal		12 months	No