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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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