Clinical trial NCT00949078: Omalizumab in the Treatment of Peanut Allergy
Official title: Effects of Omalizumab on Peanut Allergen Induced Cellular and Clinical Responses in Peanut Allergic Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Food Allergy
Peanut Allergy
Keywords: peanut
allergy
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2009-07-30
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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 Forced Expiatory Volume in 1 second (FEV1) \< 80% predicted or severe persistent asthma per National Asthma Education and Prevention Program (NAEPP) 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%, White Blood Cell (WBC) count \<4000/microliter, platelet \< 75000/microliter, creatinine \> 141.4 micromolar/L, or Aspartate Aminotransferase (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 Oral Food Challenge (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 Myocardial Infarction, 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.

Primary outcomes:
measure: Number of Participants Who Experienced a Decrease in Pn-BHR Area Under the Curve (AUC) of > 80% Compared With Baseline Values Before Week 8
timeFrame: up to 6 months
measure: Percent Change in Peanut Specific Immunoglobulin E (IgE) From Baseline to After Pn-BHR Response
timeFrame: change from baseline to up to 6 months
measure: Peanut Specific Immunoglobulin E (IgE) After Pn-BHR Response
timeFrame: up to 6 months
measure: Total Immunoglobulin E (IgE) After Pn-BHR Response
timeFrame: up to 6 months
measure: Dose of Peanut Protein Inducing Allergic Symptoms at Oral Food Challenge (OFC) 1
timeFrame: up to 8 weeks
measure: Dose of Peanut Protein Inducing Allergic Symptoms at OFC 2
timeFrame: up to 8 weeks
measure: Dose of Peanut Protein Inducing Allergic Symptoms at OFC 3
timeFrame: up to 8 weeks
measure: Omalizumab Received Before OFC 2
timeFrame: up to 6 months
measure: Omalizumab Received Before OFC 2
timeFrame: up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Robert A Wood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Sarbjit Saini, MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1056/NEJMoa022613. Epub 2003 Mar 10.