A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial

Hypersensitivity Clinical Trial

Official title:

Sublingual Immunotherapy for Peanut Allergy: A Randomized, Double-Blind, Placebo-Controlled, Phase I/II Pilot Study With a Whole Peanut Extract

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00580606
• Other study ID #: DAIT CoFAR4
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2007
• Est. completion date: December 2014

Study information

• Verified date: August 2019
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2014
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Food Hypersensitivity
• Hypersensitivity
• Hypersensitivity, Immediate
• Immediate Hypersensitivity
• Peanut Hypersensitivity

Intervention

Drug:
• Glycerinated peanut allergenic extract
Glycerinated peanut extract delivered sublingually.
• Placebo for peanut extract (glycerin)
Placebo (glycerin) delivered sublingually.

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	University of North Carolina	Durham	North Carolina
United States	University of Arkansas	Little Rock	Arkansas
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Consortium of Food Allergy Research

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 rand — View 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. Review. — View Citation

Enrique E, Cisteró-Bahíma A. Specific immunotherapy for food allergy: basic principles and clinical aspects. Curr Opin Allergy Clin Immunol. 2006 Dec;6(6):466-9. Review. — View 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 randomiz — View 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. Epub 2007 Aug 8. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Desensitization Assessment: Participants who successfully consumed without dose-limiting symptoms 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 during a double-blind placebo-controlled oral food challenge were counted as successes.	Week 44 (Double Blind Period)
Secondary	Percent of Participants Who Achieved a Maintenance Dose of 1,386 mcg	During the build-up phase, escalation was to occur every 2 weeks until the 1,386 mcg maintenance dose was reached. The maximum time allowed for the build-up phase was 36 weeks; the dose achieved by 36 weeks was considered the maintenance dose.	Week 44 (Double Blind Period)
Secondary	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	Desensitization Assessment: Participants who successfully consumed without dose-limiting symptoms 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 during a double-blind placebo-controlled oral food challenge were counted as successes.	Week 44 after initiating crossover open label peanut protein consumption
Secondary	Percent of Crossover Participants Who Achieved an Open Label Peanut Protein Consumption Maintenance Dose of 3,696 mcg	During the build-up phase, escalation was to occur every 2 weeks until the 3,696 mcg maintenance dose was reached. The maximum time allowed for the build-up phase was 36 weeks; the dose achieved by 36 weeks was considered the maintenance dose.	Week 44 after initiating crossover open label peanut protein consumption
Secondary	Number of Participants With Serious Adverse Events (SAEs)	This study graded the severity of Adverse Events experienced by participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.	Baseline through Week 44 (Double Blind Period)
Secondary	Number of Crossover Participants With Serious Adverse Events (SAEs) During 44 Weeks of Open Label Peanut Protein Consumption	All subjects who were in the Placebo group during the double-blind phase of the study who initiated crossover peanut sublingual immunotherapy during the open label phase of the study will be included.	Initiation of open label peanut protein study therapy through Week 44 of open label peanut protein consumption
Secondary	Percent of Participants Who Successfully Consumed 10,000 mg of Peanut Powder	Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of peanut powder during a double-blind placebo-controlled oral food challenge were then given an open feeding of peanut butter and those who successfully consumed the open feeding were counted as successes.	Approximately 8 weeks after discontinuing study therapy after 3 years on maintenance study therapy

External Links

•   Main Areas of Focus: Consortium of Food Allergy Research (CoFAR)
•   National Institute of Allergy and Infectious Diseases (NIAID)