Peanut Allergy
Conditions
Keywords
AR101 (Characterized Peanut Allergen), Characterized Peanut Allergen, CPNA (Characterized Peanut Allergen), OIT (oral immunotherapy), Oral Immunotherapy, Peanut Allergy, Allergy, Peanut-Allergic Children, Peanut-Allergic Adults, Desensitization
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of AR101 through reduction in clinical reactivity to peanut allergen in peanut-allergic children and adults.
Detailed description
This is an international, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of AR101 in a characterized desensitization oral immunotherapy regimen in peanut-allergic individuals.
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 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age 4 through 55 years * Clinical history of allergy to peanuts or peanut-containing foods * Serum immunoglobulin E (IgE) to peanut ≥0.35 kUA/L (kilos of allergen-specific units per liter, determined by UniCAP™\* within the past 12 months) and/or a skin prick test (SPT) to peanut ≥3 mm compared to control * Experience dose-limiting symptoms at or before the 100 mg challenge dose of peanut protein (measured as 200 mg of peanut flour) on Screening DBPCFC conducted in accordance with PRACTALL\*\* guidelines * Not be residing at the same address as another subject in this or any peanut OIT study UniCAP™\*: a laboratory system for routine diagnostic testing of allergy and tool for basic studies on allergens and antibodies PRACTALL\*\*: PRACTical issues in ALLergology Joint United States/European Union Initiative Key
Exclusion criteria
* History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension * History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of Screening DBPCFC * History of chronic disease (other than asthma, atopic dermatitis, or allergic rhinitis) that is, or is at significant risk of becoming, unstable or requiring a change in chronic therapeutic regimen * 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 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 steroid medication use * History of a mast cell disorder, including mastocytosis, urticarial pigmentosa, and hereditary or idiopathic angioedema * Developing dose-limiting symptoms in reaction to the placebo part of the Screening DBPCFC * Having the same place of residence as another subject in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 12 months | The percentage 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 |
|---|---|---|
| Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 12 months | The percentage 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. |
| Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 12 months | The percentage 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. |
| Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 12 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
Canada, Denmark, Germany, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AR101 AR101 drug product provided in two presentations. These were peanut protein in pull-apart capsules or sachets.
Pull-apart capsules contained 0.5, 1, 10, 20 and 100mg of peanut protein and sealed, foil-laminated sachets contained 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. | 413 |
| Placebo A Placebo matching the AR101 drug product was supplied in two presentations. These were pull-apart capsules matching the 0.5, 1, 10, 20 and 100mg peanut capsules but containing no peanut protein and sealed, foil-laminated 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. The sachets were used during the Maintenance phase. | 138 |
| Total | 551 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 51 | 3 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Other reasons | 5 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 41 | 7 |
Baseline characteristics
| Characteristic | AR101 | Total | Placebo |
|---|---|---|---|
| Age, Customized Age customized categorical Adolescents (12-17 years) | 134 Participants | 169 Participants | 35 Participants |
| Age, Customized Age customized categorical Adults (18-55 years) | 41 Participants | 55 Participants | 14 Participants |
| Age, Customized Age customized categorical Children (4-11 years) | 238 Participants | 327 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 47 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 383 Participants | 504 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 44 Participants | 54 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 32 Participants | 48 Participants | 16 Participants |
| Race (NIH/OMB) White | 329 Participants | 438 Participants | 109 Participants |
| Sex: Female, Male Female | 180 Participants | 236 Participants | 56 Participants |
| Sex: Female, Male Male | 233 Participants | 315 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 372 | 0 / 124 | 0 / 41 | 0 / 14 |
| other Total, other adverse events | 367 / 372 | 118 / 124 | 40 / 41 | 13 / 14 |
| serious Total, serious adverse events | 8 / 372 | 1 / 124 | 2 / 41 | 1 / 14 |
Outcome results
Primary
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
The percentage 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: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 | Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 250 Participants |
| Placebo | Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 5 Participants |
Comparison: Treatment difference at 600 mgp-value: <0.000195% CI: [53, 73.3]Farrington-Manning test
Secondary
Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
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: 12 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AR101 | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | None | 140 Participants |
| AR101 | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | Moderate | 94 Participants |
| AR101 | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | Mild | 119 Participants |
| AR101 | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | Severe or worse | 19 Participants |
| Placebo | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | Mild | 35 Participants |
| Placebo | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | None | 3 Participants |
| Placebo | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | Severe or worse | 13 Participants |
| Placebo | Percentage of Subjects Ages 4-17 by Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein During the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | Moderate | 73 Participants |
Comparison: Treatment difference in maximum severityp-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
The percentage 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: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 | Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 187 Participants |
| Placebo | Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 3 Participants |
Comparison: Treatment difference at 1000 mgp-value: <0.000195% CI: [38, 57.7]Farrington-Manning test
Secondary
Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
The percentage 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: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 | Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 285 Participants |
| Placebo | Percentage of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Double-Blind, Placebo-Controlled Food Challenge (DBPCFC) | 10 Participants |
Comparison: Treatment difference at 300 mgp-value: <0.000195% CI: [58.6, 78.5]Farrington-Manning test