Clinical trial NCT00580606: A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial
Official title: Sublingual Immunotherapy for Peanut Allergy: A Randomized, Double-Blind, Placebo-Controlled, Phase I/II Pilot Study With a Whole Peanut Extract
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Food Hypersensitivity
Hypersensitivity
Immediate Hypersensitivity
Peanut Hypersensitivity
Keywords: Food Allergy
Peanut Allergy
Sublingual Immunotherapy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Consortium of Food Allergy Research
First posted: 2007-12-25
Enrollment: 40
Sex: ALL
Minimum age (years): 12
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and immune response to daily sublingual (under the tongue) immunotherapy (SLIT) with peanut extract in adults and children with peanut allergies.

Detailed description: Peanut allergy is a common ailment in the United States. Research suggests that the prevalence of peanut allergy in the United States has doubled over the last 5 years. Currently, the only effective treatment for peanut allergy is a peanut-free diet and quick access to self-injectable epinephrine in the event of peanut exposure. The sublingual route is a potential method to administer immunotherapy for the treatment of food allergies. The intent of this study is to induce desensitization and eventually tolerance to peanut protein and evaluate the safety and immunologic effects of daily sublingual immunotherapy (SLIT) for individuals with peanut allergy. The trial will enroll 40 participants. After the first 10 participants between the ages of 18 and 40 are enrolled, safety information will be reviewed. If there are no safety concerns, the study will continue to enroll the remaining participants between the ages of 12 and 40.

This clinical trial will last 172 to 216 weeks. Participants will be randomly assigned to receive peanut SLIT or placebo SLIT. All participants will have an entry oral food challenge (OFC). The treatment group will receive gradual dosing escalations of peanut SLIT and maintenance therapy over a 44-week period, followed by another OFC. Following the OFC, participants will be unblinded, and the placebo group will receive peanut SLIT escalated to a higher maximum dose than the first treatment group. Maintenance therapy will continue for both groups for more than 2 years.

Study visits will occur every 2 weeks during dosing escalations of peanut SLIT, followed by visits gradually spacing out during maintenance to every 12 weeks. At selected visits, a physical examination, skin prick tests, blood and urine collection, and atopic dermatitis and asthma evaluations will occur. Approximately 6 OFCs will be administered to each participant throughout the course of the study. Additionally, 10 participants will be enrolled as control participants who will not receive any study therapy and will only have blood drawn at 3 visits throughout the course of the trial.

Eligibility criteria: Inclusion Criteria:

* Physician-diagnosed peanut allergy OR convincing clinical history of peanut allergy
* Reacts to a cumulative dose of 2,000 mg or less of peanut powder
* Positive peanut allergy skin prick test OR detectable serum peanut-specific IgE level
* Willing to use an acceptable method of contraception for the duration of the study
* Ability to perform spirometry maneuver in accordance with the American Thoracic Society guidelines

Exclusion Criteria:

* History of severe anaphylaxis to peanut
* Currently participating in a study using a new investigational new drug
* Participation in any interventional study for the treatment of food allergy in the 12 months prior to study entry
* Allergic to placebo ingredients (glycerin or oat flour) OR reacts to any dose of placebo during study entry oral food challenge (OFC)
* Currently in a buildup phase of any allergy immunotherapy
* Poor control of atopic dermatitis
* Moderate or severe asthma despite therapy
* Current treatment with greater than medium daily doses of inhaled corticosteroids
* Use of steroid medications
* Use of omalizumab or other nontraditional forms of allergen immunomodulatory therapy (not including corticosteroids) or biologic therapy in the 12 months prior to study entry
* Use of beta blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or calcium channel blockers
* Inability to discontinue antihistamines for skin testing and OFCs
* History of ischemic cardiovascular disease
* History of alcohol or drug abuse
* Other significant medical conditions that, in the opinion of the investigator, prevent participation in the study
* Previous intubation due to allergies or asthma
* Uncontrolled high blood pressure
* Pregnancy or breastfeeding

Primary outcomes:
measure: Percent of Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge
timeFrame: Week 44 (Double Blind Period)
Secondary outcomes:
measure: Percent of Participants Who Achieved a Maintenance Dose of 1,386 mcg
timeFrame: Week 44 (Double Blind Period)
measure: Percent of Crossover Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge After 44 Weeks of Open Label Peanut Protein Consumption
timeFrame: Week 44 after initiating crossover open label peanut protein consumption
measure: Percent of Crossover Participants Who Achieved an Open Label Peanut Protein Consumption Maintenance Dose of 3,696 mcg
timeFrame: Week 44 after initiating crossover open label peanut protein consumption
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Baseline through Week 44 (Double Blind Period)
measure: Number of Crossover Participants With Serious Adverse Events (SAEs) During 44 Weeks of Open Label Peanut Protein Consumption
timeFrame: Initiation of open label peanut protein study therapy through Week 44 of open label peanut protein consumption
measure: Percent of Participants Who Successfully Consumed 10,000 mg of Peanut Powder
timeFrame: Approximately 8 weeks after discontinuing study therapy after 3 years on maintenance study therapy
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Durham
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Duke University
name: Wesley Burks, MD
role: STUDY_CHAIR
affiliation: National Jewish Health
name: David Fleischer, MD
role: STUDY_CHAIR
affiliation: Icahn School of Medicine at Mount Sinai
name: Hugh A. Sampson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arkansas Children's Hospital Research Institute
name: Stacie Jones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Robert Wood, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Leon MP, Rolland JM, O'Hehir RE. The peanut allergy epidemic: allergen molecular characterisation and prospects for specific therapy. Expert Rev Mol Med. 2007 Jan 9;9(1):1-18. doi: 10.1017/S1462399407000208.
citation: Enrique E, Cistero-Bahima A. Specific immunotherapy for food allergy: basic principles and clinical aspects. Curr Opin Allergy Clin Immunol. 2006 Dec;6(6):466-9. doi: 10.1097/01.all.0000246618.41871.a4.
citation: Sicherer SH, Sampson HA. Peanut allergy: emerging concepts and approaches for an apparent epidemic. J Allergy Clin Immunol. 2007 Sep;120(3):491-503; quiz 504-5. doi: 10.1016/j.jaci.2007.07.015. Epub 2007 Aug 8.
citation: Fleischer DM, Burks AW, Vickery BP, Scurlock AM, Wood RA, Jones SM, Sicherer SH, Liu AH, Stablein D, Henning AK, Mayer L, Lindblad R, Plaut M, Sampson HA; Consortium of Food Allergy Research (CoFAR). Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol. 2013 Jan;131(1):119-27.e1-7. doi: 10.1016/j.jaci.2012.11.011.
citation: Burks AW, Wood RA, Jones SM, Sicherer SH, Fleischer DM, Scurlock AM, Vickery BP, Liu AH, Henning AK, Lindblad R, Dawson P, Plaut M, Sampson HA; Consortium of Food Allergy Research. Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial. J Allergy Clin Immunol. 2015 May;135(5):1240-8.e1-3. doi: 10.1016/j.jaci.2014.12.1917. Epub 2015 Feb 3.