Peanut Allergy
Conditions
Keywords
Characterized Peanut Allergen, Peanut, OIT, Oral Desensitization, Peanut Allergen, Allergy, Peanut Allergy, Peanut-Allergic Children, Children, Peanut-Allergic Adults
Brief summary
This is a multi-center, randomized, double-blind placebo controlled study of efficacy and safety of characterized peanut oral immunotherapy in peanut allergic individuals.
Detailed description
This is a multicenter, randomized, double-blind placebo controlled study of efficacy and safety of characterized peanut OIT in peanut allergic individuals. All eligible subjects will receive an escalating dose of CPNA or placebo. Approximately 50 subjects will be randomized 1:1 to peanut OIT or placebo.
Interventions
BIOLOGICALAR101 powder provided in capsules
Study product formulated to contain peanut protein at different dosage strengths for use as defined in the protocol
BIOLOGICALPlacebo powder provided in capsules
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
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 26 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Ages 4 through 26 years, inclusive * Clinical history of allergy to peanuts or peanut-containing foods * Serum IgE to peanut \>0.35 kU/L (determined by UniCAP within the past 12 months) and/or a SPT to peanut \>3 mm compared to control * Experience dose-limiting symptoms at or before the 100mg dose of peanut protein (measured as 200 mg of peanut flour) on abbreviated screening OFC conducted via PRACTALL guidelines * Use of birth control by females of child-bearing potential Key
Exclusion criteria
* History of Cardiovascular disease * History of frequent or repeated, severe or life-threatening episodes of anaphylactic shock * History of other chronic disease * History of eosinophilic gastrointestinal disease * Severe asthma * Mild or moderate asthma if uncontrolled * Use of omalizumab within the past 6 months or current use of other non-traditional forms of allergen immunotherapy * Use of beta-blockers(oral), angiotensin-converting enzyme (ACE) * Pregnancy, lactation * Having the same place of residence as another study subject * Participation in an interventional clinical trial 30 days prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Tolerate at Least 300 mg (443 mg Cumulative) of Peanut Protein With no More Than Mild Symptoms at the Exit DBPCFC | 6-9 Months | The primary endpoint was the percentage of subjects who achieved desensitization, as determined by tolerating at least 300 mg (443 mg cumulative) of peanut protein at the Exit Double Blind Placebo Controlled Food Challenge (DBPCFC) with no more than mild symptoms (i.e., desensitization responders) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Tolerated Dose of Peanut Protein at the Exit DBPCFC | 6-9 months | The change in maximum tolerated dose of peanut protein from baseline (screening) to the Exit Double-Blind, Placebo-Controlled Food Challenge |
| Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 6-9 months | — |
| Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | 6-9 months | — |
| Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | 6-9 months | — |
| Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Baseline, 6-9 months | — |
Countries
United States
Participant flow
Pre-assignment details
A total of 67 subjects signed the informed consent and went through the screening process. 11 subjects failed screening, resulting in 56 subjects being enrolled and initially randomized. The randomized population comprised 29 subjects in the AR101 group and 27 subjects in the placebo group. The final intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment) had one fewer subject in the placebo group (n=26).
Participants by arm
| Arm | Count |
|---|---|
| AR101 Powder Provided in Capsules Study product provided as peanut protein in pull-apart capsules
AR101 powder provided in capsules: Study product formulated to contain peanut protein at different dosage strengths for use as defined in the protocol | 29 |
| Placebo Powder Provided in Capsules Placebo formulation in pull-apart capsules containing only inactive ingredients
Placebo powder provided in capsules: Study product formulated to contain only inactive ingredients for use as defined in the protocol | 26 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Powder Provided in Capsules | Total | AR101 Powder Provided in Capsules |
|---|---|---|---|
| Age, Continuous | 8.0 years | 8.0 years | 7.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 55 Participants | 29 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 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 | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 20 Participants | 46 Participants | 26 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 16 Participants | 36 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 26 |
| other Total, other adverse events | 28 / 29 | 22 / 26 |
| serious Total, serious adverse events | 1 / 29 | 1 / 26 |
Outcome results
Primary
The Percentage of Subjects Who Tolerate at Least 300 mg (443 mg Cumulative) of Peanut Protein With no More Than Mild Symptoms at the Exit DBPCFC
The primary endpoint was the percentage of subjects who achieved desensitization, as determined by tolerating at least 300 mg (443 mg cumulative) of peanut protein at the Exit Double Blind Placebo Controlled Food Challenge (DBPCFC) with no more than mild symptoms (i.e., desensitization responders)
Time frame: 6-9 Months
Population: The number of participants analyzed per outcome measure reflects the intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AR101 Powder Provided in Capsules | The Percentage of Subjects Who Tolerate at Least 300 mg (443 mg Cumulative) of Peanut Protein With no More Than Mild Symptoms at the Exit DBPCFC | 23 Participants |
| Placebo Powder Provided in Capsules | The Percentage of Subjects Who Tolerate at Least 300 mg (443 mg Cumulative) of Peanut Protein With no More Than Mild Symptoms at the Exit DBPCFC | 5 Participants |
p-value: <0.000195% CI: [35, 79]Fisher Exact
Secondary
Change From Baseline in Maximum Tolerated Dose of Peanut Protein at the Exit DBPCFC
The change in maximum tolerated dose of peanut protein from baseline (screening) to the Exit Double-Blind, Placebo-Controlled Food Challenge
Time frame: 6-9 months
Population: The number of participants analyzed per outcome measure reflects the intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| AR101 Powder Provided in Capsules | Change From Baseline in Maximum Tolerated Dose of Peanut Protein at the Exit DBPCFC | 1.254 Change from baseline in MTD (log10 mg) |
| Placebo Powder Provided in Capsules | Change From Baseline in Maximum Tolerated Dose of Peanut Protein at the Exit DBPCFC | 0.341 Change from baseline in MTD (log10 mg) |
Comparison: MTD for the baseline and Exit DBPCFC are transformed back to log10 scale before calculations. A value of 0.3 mg is substituted for subjects who could not tolerate the lowest DBPCFC dose before log10 transformation.p-value: <0.000195% CI: [0.5184, 1.3065]ANCOVA
Secondary
Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline
Time frame: Baseline, 6-9 months
Population: The number of participants analyzed per outcome measure reflects the intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AR101 Powder Provided in Capsules | Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Peanut Wheal, Baseline (mm) | 14.1 millimeter |
| AR101 Powder Provided in Capsules | Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Peanut Wheal, Exit (mm) | 7.1 millimeter |
| AR101 Powder Provided in Capsules | Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Change in Peanut Wheel from Baseline (mm) | -7.0 millimeter |
| Placebo Powder Provided in Capsules | Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Peanut Wheal, Baseline (mm) | 13.7 millimeter |
| Placebo Powder Provided in Capsules | Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Peanut Wheal, Exit (mm) | 11.8 millimeter |
| Placebo Powder Provided in Capsules | Change in Skin Prick Test (SPT) Mean Peanut Wheal Diameter Results From Baseline | Change in Peanut Wheel from Baseline (mm) | -1.8 millimeter |
Secondary
Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC
Time frame: 6-9 months
Population: The number of participants analyzed per outcome measure reflects the intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment)~Relative change from baseline is calculated as the ratio of exit visit result to the baseline result, within treatment group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| AR101 Powder Provided in Capsules | Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | Peanut-Specific IgE, Baseline | 32.571 kUA/L |
| AR101 Powder Provided in Capsules | Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | Peanut-Specific IgE, Exit | 36.889 kUA/L |
| AR101 Powder Provided in Capsules | Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | Relative Change From Baseline of Peanut-Specific IgGE | 1.231 kUA/L |
| Placebo Powder Provided in Capsules | Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | Peanut-Specific IgE, Baseline | 53.839 kUA/L |
| Placebo Powder Provided in Capsules | Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | Peanut-Specific IgE, Exit | 57.060 kUA/L |
| Placebo Powder Provided in Capsules | Changes in Peanut-Specific IgE From Baseline to Exit DBPCFC | Relative Change From Baseline of Peanut-Specific IgGE | 1.060 kUA/L |
Secondary
Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC
Time frame: 6-9 months
Population: The number of participants analyzed per outcome measure reflects the intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment)~Relative change from baseline is calculated as the ratio of exit visit result to the baseline result, within treatment group.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| AR101 Powder Provided in Capsules | Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | Peanut-Specific IgG4, Baseline | 0.734 μg/mL |
| AR101 Powder Provided in Capsules | Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | Peanut-Specific IgG4, Exit | 3.609 μg/mL |
| AR101 Powder Provided in Capsules | Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | Relative Change From Baseline of Peanut-Specific IgG4 | 5.068 μg/mL |
| Placebo Powder Provided in Capsules | Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | Peanut-Specific IgG4, Baseline | 0.510 μg/mL |
| Placebo Powder Provided in Capsules | Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | Peanut-Specific IgG4, Exit | 0.540 μg/mL |
| Placebo Powder Provided in Capsules | Changes in Peanut-Specific IgG4 From Baseline to Exit DBPCFC | Relative Change From Baseline of Peanut-Specific IgG4 | 1.066 μg/mL |
Secondary
Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC
Time frame: 6-9 months
Population: The number of participants analyzed per outcome measure reflects the intent-to-treat (ITT) population (subjects who received at least 1 dose of randomized study treatment)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 10 mg | 3 Participants |
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 100 mg | 0 Participants |
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 3 mg | 2 Participants |
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 300 mg | 5 Participants |
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 30 mg | 1 Participants |
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 600 mg | 18 Participants |
| AR101 Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 0.3 mg | 0 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 600 mg | 0 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 0.3 mg | 1 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 3 mg | 2 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 10 mg | 7 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 30 mg | 5 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 100 mg | 6 Participants |
| Placebo Powder Provided in Capsules | Number of Participants by Maximum Dose Achieved With no or Mild Symptoms at Exit DBPCFC | 300 mg | 5 Participants |