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

NCT ID: NCT00580606

Last Updated: 2019-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2014-12-31

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.

Conditions

Food Hypersensitivity; Hypersensitivity; Immediate Hypersensitivity; Peanut Hypersensitivity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Low Dose Peanut SLIT (Double Blind to Open Label)

Subjects ingest peanut protein (glycerinated peanut allergenic extract) daily starting with 0.000165 mcg, followed by a build-up phase (escalating peanut doses every 2 weeks, achieving maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for \>= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and continue on an open label peanut protein maintenance dose of 1,386 mcg/day or may attempt escalation up to this dose. Subjects who at the Week 116 OFC are unable to consume \>= 5,000 mg peanut powder or 10-fold the amount of peanut powder compared to the baseline OFC will discontinue study therapy. SLIT=Sublingual Immunotherapy.

Group Type: EXPERIMENTAL

Glycerinated peanut allergenic extract

Intervention Type: DRUG

Glycerinated peanut extract delivered sublingually.

Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL)

Subjects ingest placebo (glycerin) daily beginning with a dose of 0.000165 mcg, followed by a build-up phase (escalating placebo doses every 2 weeks, achieving a maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for \>= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and subjects no longer receive placebo dosing but are crossed over and receive open label high dose peanut SLIT; the study procedures and schedule are the same as for the Low Dose Peanut SLIT group, the only difference is the maximum maintenance dose is almost 3-fold higher at 3,696 mcg/day. DB=Double Blind, SLIT=Sublingual Immunotherapy, OL=Open Label.

Group Type: PLACEBO_COMPARATOR

Placebo for peanut extract (glycerin)

Intervention Type: DRUG

Placebo (glycerin) delivered sublingually.

Interventions

Glycerinated peanut allergenic extract

Glycerinated peanut extract delivered sublingually.

Intervention Type: DRUG

Placebo for peanut extract (glycerin)

Placebo (glycerin) delivered sublingually.

Intervention Type: DRUG

Other Intervention Names

Peanut SLIT; Placebo

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Consortium of Food Allergy Research

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wesley Burks, MD

Role: STUDY_CHAIR

Duke University

David Fleischer, MD

Role: STUDY_CHAIR

National Jewish Health

Hugh A. Sampson, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Stacie Jones, MD

Role: PRINCIPAL_INVESTIGATOR

Arkansas Children's Hospital Research Institute

Robert Wood, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

University of Arkansas

Little Rock, Arkansas, United States

National Jewish Medical and Research Center

Denver, Colorado, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Mount Sinai School of Medicine

New York, New York, United States

University of North Carolina

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17210088 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17088653 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17689596 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23265698 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25656999 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/research/consortium-food-allergy-research

Main Areas of Focus: Consortium of Food Allergy Research (CoFAR)

Other Identifiers

DAIT CoFAR4

Identifier Type: -

Identifier Source: org_study_id