Food Hypersensitivity, Hypersensitivity, Immediate Hypersensitivity, Peanut Hypersensitivity
Conditions
Keywords
Food Allergy, Peanut Allergy, Sublingual Immunotherapy
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.
Interventions
DRUGGlycerinated peanut allergenic extract
Glycerinated peanut extract delivered sublingually.
DRUGPlacebo for peanut extract (glycerin)
Placebo (glycerin) delivered sublingually.
Sponsors
Consortium of Food Allergy Research
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 44 (Double Blind Period) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 44 after initiating crossover 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 | Week 44 after initiating crossover open label peanut protein consumption | 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. |
| Percent of Participants Who Achieved a Maintenance Dose of 1,386 mcg | Week 44 (Double Blind Period) | 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. |
| Number of Crossover Participants With Serious Adverse Events (SAEs) During 44 Weeks of Open Label Peanut Protein Consumption | Initiation of open label peanut protein study therapy through Week 44 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. |
| Percent of Participants Who Successfully Consumed 10,000 mg of Peanut Powder | Approximately 8 weeks after discontinuing study therapy after 3 years on maintenance study therapy | 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. |
| Number of Participants With Serious Adverse Events (SAEs) | Baseline through Week 44 (Double Blind Period) | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at five university-based medical centers in the United States (Mt. Sinai School of Medicine, Johns Hopkins University, Duke University, National Jewish Medical Center, University of Arkansas Children's Hospital from April 2008 to January 2010.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 20 |
| 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. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open Label (OL) | Dosing Symptoms | 0 | 1 |
| Open Label (OL) | Lack of Efficacy at Week 116 OFC | 2 | 1 |
| Open Label (OL) | Lost to Follow-up | 0 | 1 |
| Open Label (OL) | Needed Prohibited Medication | 0 | 1 |
| Open Label (OL) | Non-compliance | 2 | 0 |
| Open Label (OL) | Physician Decision | 1 | 1 |
| Open Label (OL) | Pregnancy | 0 | 1 |
| Open Label (OL) | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Low Dose Peanut SLIT (Double Blind to Open Label) | Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL) | Total |
|---|---|---|---|
| Age at Initial Peanut Allergic Reaction | 4.6 years STANDARD_DEVIATION 6.9 | 1.9 years STANDARD_DEVIATION 1.5 | 3.3 years STANDARD_DEVIATION 5.2 |
| Age, Categorical <=18 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 17.2 years STANDARD_DEVIATION 7.6 | 16.5 years STANDARD_DEVIATION 3.5 | 16.8 years STANDARD_DEVIATION 5.8 |
| Atopic Dermatitis Total Score | 1.1 Scores on a scale STANDARD_DEVIATION 1.7 | 0.9 Scores on a scale STANDARD_DEVIATION 1.6 | 1.0 Scores on a scale STANDARD_DEVIATION 1.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 20 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Peanut IgE | 33.6 kUA/L STANDARD_DEVIATION 38.1 | 47.1 kUA/L STANDARD_DEVIATION 58 | 40.4 kUA/L STANDARD_DEVIATION 48.9 |
| Peanut Skin Prick Test Score | 14.0 mm STANDARD_DEVIATION 6.9 | 12.4 mm STANDARD_DEVIATION 4.6 | 13.2 mm STANDARD_DEVIATION 5.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 19 Participants | 36 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
| Total IgE | 407.8 kU/L STANDARD_DEVIATION 254.1 | 330.5 kU/L STANDARD_DEVIATION 305 | 369.1 kU/L STANDARD_DEVIATION 279.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 20 | 20 / 20 | 17 / 17 | 17 / 18 | 15 / 17 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 | 0 / 17 | 1 / 18 | 0 / 17 |
Outcome results
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.
Time frame: Week 44 (Double Blind Period)
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | 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 | 70 Percentage of participants |
| Placebo (Double Blind) | 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 | 15 Percentage of participants |
Comparison: Number 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 OFC was compared using Barnard's Statistic with the null hypothesis that there was no difference between treatment groups.p-value: <0.00195% CI: [22.2, 77.6]Barnard's Statistic
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.
Time frame: Initiation of open label peanut protein study therapy through Week 44 of open label peanut protein consumption
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | Number of Crossover Participants With Serious Adverse Events (SAEs) During 44 Weeks of Open Label Peanut Protein Consumption | 0 participants |
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.
Time frame: Baseline through Week 44 (Double Blind Period)
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | Number of Participants With Serious Adverse Events (SAEs) | 1 participants |
| Placebo (Double Blind) | Number of Participants With Serious Adverse Events (SAEs) | 0 participants |
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.
Time frame: Week 44 after initiating crossover open label peanut protein consumption
Population: All subjects in the Placebo group during the double-blind period who crossed over to open label high dose peanut sublingual immunotherapy were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | Percent of Crossover Participants Who Achieved an Open Label Peanut Protein Consumption Maintenance Dose of 3,696 mcg | 88.2 Percentage of participants |
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.
Time frame: Week 44 after initiating crossover open label peanut protein consumption
Population: Subjects in the Placebo group during the double-blind period who crossed over to open label high dose peanut sublingual immunotherapy were included except for 1 subject who refused the crossover Week 44 OFC and could not be evaluated. 4 subjects who discontinued dosing prior to the crossover Week 44 OFC were counted as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | 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 | 43.8 Percentage of participants |
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.
Time frame: Week 44 (Double Blind Period)
Population: The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | Percent of Participants Who Achieved a Maintenance Dose of 1,386 mcg | 85.0 Percentage of participants |
| Placebo (Double Blind) | Percent of Participants Who Achieved a Maintenance Dose of 1,386 mcg | 95.0 Percentage of participants |
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.
Time frame: Approximately 8 weeks after discontinuing study therapy after 3 years on maintenance study therapy
Population: All subjects randomized to the Low Dose Peanut SLIT group and all subjects randomized to the Placebo group who crossed over to open label high dose peanut sublingual immunotherapy were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Peanut SLIT (Double Blind) | Percent of Participants Who Successfully Consumed 10,000 mg of Peanut Powder | 10.0 percentage of participants |
| Placebo (Double Blind) | Percent of Participants Who Successfully Consumed 10,000 mg of Peanut Powder | 11.8 percentage of participants |