Peanut Allergy
Conditions
Keywords
AR101, Characterized Peanut Allergen, CPNA (Characterized Peanut Allergen), OIT (oral immunotherapy), Peanut Allergy, Peanut-Allergic Children, Desensitization, ARTEMIS, Allergy
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of AR101 through oral immunotherapy (OIT) in peanut-allergic children.
Detailed description
This is a European, multicenter, double-blind, randomized, placebo-controlled 2-arm study of the efficacy and safety of AR101 in peanut-allergic children.
Interventions
Study product formulated to contain peanut protein at different dosage strengths for use as defined in the protocol
Study product formulated to contain only inactive ingredients for use as defined in the protocol
Sponsors
Aimmune Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age 4 to 17 years, inclusive * Clinical history of allergy to peanuts * Serum SPT ≥ 3 mm greater than control and/or psIgE ≥ 0.35 kUa/L * Dose limiting symptoms after consuming a single dose of peanut protein ≤ 300 mg * Written informed consent from the subject's parent/guardian * Written assent from the subject as appropriate (per local regulatory requirements) * Use of effective birth control by sexually active female subjects of childbearing potential Key
Exclusion criteria
* History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension * History of severe asthma (NHLBI criteria steps 5 or 6), or mild to moderate asthma (2007 NHLBI criteria steps 1-4) that is uncontrolled or difficult to control * History of severe or life threatening episode of anaphylaxis or anaphylactic shock within 60 days of screening * History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia or recurrent gastrointestinal symptoms of undiagnosed etiology * History of a mast cell disorder, including mastocytosis, urticaria pigmentosa, chronic idiopathic or chronic physical urticaria beyond simple dermatographism (e.g., cold urticaria, cholinergic urticaria), and hereditary or idiopathic angioedema * Any other condition that, in the opinion of the Investigator, precludes participation for reasons of safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Oral Food Challenge. | Approximately 9 months | The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Oral Food Challenge | Approximately 9 months | The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge. |
| Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Oral Food Challenge. | Approximately 9 months | The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge. |
| Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Approximately 9 months | The maximum severity of symptoms on 4 levels: 0-None, 1-Mild, 2-Moderate, 3-Severe or higher (severe, life threatening, fatal) observed in the DBPCFC at any dose (1000 mg or lower) |
Countries
France, Germany, Ireland, Italy, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AR101 AR101 drug product was supplied in 2 presentations. These were pull-apart capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein.
The capsules were used during the Initial Escalation and Up-dosing phases of the study. The sachets were used during the Maintenance phase. | 132 |
| Placebo A placebo matching the AR101 drug product was supplied in 2 presentations. These were capsules matching the 0.5, 1, 10, 20 and 100mg peanut capsules but containing no peanut protein, and sealed sachets matching the peanut protein sachets but without any peanut protein. The capsules were used during the Initial Escalation and Up-dosing phases of the study, while the sachets were used during the Maintenance phase. | 43 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other reasons | 5 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | AR101 | Placebo | Total |
|---|---|---|---|
| Age, Customized Adolescents (12-17 years) | 35 Participants | 13 Participants | 48 Participants |
| Age, Customized Children (4-11 years) | 97 Participants | 30 Participants | 127 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants | 39 Participants | 158 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 4 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants | 7 Participants | 30 Participants |
| Race (NIH/OMB) White | 106 Participants | 34 Participants | 140 Participants |
| Region of Enrollment France | 12 participants | 5 participants | 17 participants |
| Region of Enrollment Germany | 21 participants | 7 participants | 28 participants |
| Region of Enrollment Ireland | 20 participants | 6 participants | 26 participants |
| Region of Enrollment Italy | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Spain | 20 participants | 6 participants | 26 participants |
| Region of Enrollment Sweden | 8 participants | 3 participants | 11 participants |
| Region of Enrollment United Kingdom | 46 participants | 13 participants | 59 participants |
| Sex: Female, Male Female | 64 Participants | 16 Participants | 80 Participants |
| Sex: Female, Male Male | 68 Participants | 27 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 132 | 0 / 43 |
| other Total, other adverse events | 130 / 132 | 42 / 43 |
| serious Total, serious adverse events | 1 / 132 | 2 / 43 |
Outcome results
Primary
The Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Oral Food Challenge.
The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.
Time frame: Approximately 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 | The Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Oral Food Challenge. | 77 Participants |
| Placebo | The Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Oral Food Challenge. | 1 Participants |
Comparison: Treatment difference at 1000 mgp-value: <0.000195% CI: [44.1, 65.2]Fisher Exact
Secondary
Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge
The maximum severity of symptoms on 4 levels: 0-None, 1-Mild, 2-Moderate, 3-Severe or higher (severe, life threatening, fatal) observed in the DBPCFC at any dose (1000 mg or lower)
Time frame: Approximately 9 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AR101 | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | None | 47 Participants |
| AR101 | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Mild | 55 Participants |
| AR101 | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Moderate | 24 Participants |
| AR101 | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Severe or higher | 6 Participants |
| Placebo | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Severe or higher | 7 Participants |
| Placebo | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | None | 0 Participants |
| Placebo | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Moderate | 20 Participants |
| Placebo | Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge | Mild | 16 Participants |
Comparison: Treatment difference in Maximum Severityp-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Oral Food Challenge.
The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.
Time frame: Approximately 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 | Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Oral Food Challenge. | 97 Participants |
| Placebo | Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Oral Food Challenge. | 7 Participants |
Comparison: Treatment difference at 300 mgp-value: <0.000195% CI: [41.2, 69.1]Fisher Exact
Secondary
Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Oral Food Challenge
The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.
Time frame: Approximately 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 | Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Oral Food Challenge | 90 Participants |
| Placebo | Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Oral Food Challenge | 4 Participants |
Comparison: Treatment difference at 600 mgp-value: <0.000195% CI: [44.2, 69.3]Fisher Exact