Peanut Allergy
Conditions
Brief summary
The primary objective of the study is to assess the tolerability of peanut protein in pediatric patients (6-17 years old) treated with dupilumab monotherapy, in which tolerability is defined as the proportion of patients who safely pass a double-blind placebo-controlled food challenge (DBPCFC) at week 24. The secondary objectives are: * To determine whether dupilumab treatment improves peanut tolerability, defined as a change in the cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC * To evaluate the safety and tolerability of dupilumab treatment in peanut allergic patients * To evaluate the effects of dupilumab treatment on the levels of peanut-specific Immunoglobulin E (IgE) * To evaluate the treatment effect of dupilumab on the average wheal size after a titrated skin prick test (SPT), as measured by area under curve (AUC) of the average wheal size induced by peanut extract at different concentrations * To assess the incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab in patients over time
Interventions
DRUGDupilumab
Dupilumab weight-based dosing will be administered subcutaneously (SC) in a single-use, pre-filled syringe every two weeks (Q2W)
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patient has a clinical history of allergy to peanuts or peanut-containing foods (symptom\[s\] of reaction due to exposure). * Experience dose-limiting symptoms at or before the challenge dose of peanut protein on screening DBPCFC conducted in accordance with Practical Issues in Allergology, Joint United States/European Union Initiative (PRACTALL) guidelines. And not experiencing dose limiting symptoms to placebo * Serum IgE to peanut of ≥10 kilo units (kUA)/L and/or a SPT to peanut ≥8 mm compared to a negative control * Patients/legal guardians must be trained on the proper use of the epinephrine autoinjector device to be allowed to enroll in the study * Patients with other known food allergies must agree to eliminate these other food items from their diet so as not to confound the safety and efficacy data from the study Key
Exclusion criteria
* Any previous exposure to marketed dupilumab or dupilumab in a clinical trial * Member of the clinical site study team or his/her immediate family * History of other chronic disease (other than asthma, AD, or allergic rhinitis) requiring therapy * History of frequent or recent severe, life-threatening episode of anaphylaxis or anaphylactic shock as defined by more than 3 episodes of anaphylaxis within the past year and/or an episode of anaphylaxis within 60 days of screening DBPCFC * History of eosinophilic gastrointestinal disease * History of eosinophilic granulomatosis with polyangiitis * Severe, unstable asthma at time of enrollment or any patient with Forced Expiratory Volume in 1 Second (FEV1) \<80% of predicted or asthma control questionnaire (ACQ)\>1.5 * Use of systemic corticosteroids within 2 months prior to screening Note: Other protocol Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 24 | At Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed the DBPCFC with at least 444 mg (cumulative) peanut protein at Week 24 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 36 | At Week 36 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC. |
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 24 | At Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed a DBPCFC with at least 1044 mg (cumulative) peanut protein at Week 24 was reported. |
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 36 | At Week 36 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC. |
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 24 | At Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed a DBPCFC with at least 2044 mg (cumulative) peanut protein at Week 24 was reported. |
| Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Weeks 24 and 36 | Weeks 24 and 36 | Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Week 24 and Week 36 was reported. |
| Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Weeks 4, 8, 12, 16, 24, and 36 | Percent change from baseline in sIgE at Weeks 4, 8, 12, 16, 24, and 36 was reported. |
| Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36 | Weeks 4, 12, 24, and 36 | The titrated SPT is the skin testing for atopic response at different concentrations of peanut extract with saline as negative control and histamine as positive controls. Wheal size induced by peanut extract at each concentration was calculated as average of largest diameter and perpendicular midpoint diameter. The AUC for titrated SPT was calculated using the mean wheal diameter versus the concentration at which the wheal diameter was measured, which was then normalized to concentration. Change from baseline in titrated SPT as measured by average wheal size AUC after peanut allergen stimulation at different concentrations at Weeks 4, 12, 24, and 36 was reported. |
| Percentage of Participants With Grade 2 or Above Allergic Reactions During the DBPCFC at Week 24 | At Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Percentage of participants with Grade 2 (Moderate) or above allergic reactions during the DBPCFC at Week 24 was reported. |
| Percentage of Participants Who Used Epinephrine as a Rescue Medication During the DBPCFC at Week 24 | At Week 24 | Percentage of participants who used Epinephrine as a rescue medication during the DBPCFC at Week 24 was reported. |
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 36 | At Week 36 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC. |
Countries
Canada, United States
Participant flow
Recruitment details
Twenty-five participants met eligibility criteria. One of the 25 participants was randomized under the original double-blind placebo-controlled protocol and received placebo-matching dupilumab. Following implementation of Protocol Amendment 1, 24 participants were enrolled under the open-label design & received open-label treatment with dupilumab.
Pre-assignment details
A double-blind placebo-controlled food challenge (DBPCFC) consisting of increasing amounts of peanut protein up to a cumulative total of 144 mg and a matching placebo challenge consisting of placebo material (oat protein) were given to confirm current peanut allergy. Food challenges were performed on different days in random order (1-day placebo, 1-day peanut protein), at least 24 hours, but not more than 7 days, apart. Both food challenge days were required to evaluate eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab Participants enrolled under open-label treatment protocol with weight of greater than or equal to (\>=) 20 kilograms (kg) and less than (\<) 60 kg received a subcutaneous (SC) injection of dupilumab 200 mg every 2 weeks (Q2W) after a loading dose of 400 mg on Day 1 up to Week 22; participants with weight of \>=60 kg received a SC injection of dupilumab 300 mg Q2W after a loading dose of 600 mg on Day 1 up to Week 22. At Week 24, all participants underwent a DBPCFC up to 2044 mg peanut protein (cumulative) or placebo to assess tolerability. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Dupilumab |
|---|---|
| Age, Continuous | 11.7 Years STANDARD_DEVIATION 3.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 24 |
| other Total, other adverse events | 0 / 1 | 11 / 24 |
| serious Total, serious adverse events | 0 / 1 | 0 / 24 |
Outcome results
Primary
Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 24
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed the DBPCFC with at least 444 mg (cumulative) peanut protein at Week 24 was reported.
Time frame: At Week 24
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 24 | 8.3 Percentage of Participants |
Secondary
Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Weeks 24 and 36
Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Week 24 and Week 36 was reported.
Time frame: Weeks 24 and 36
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Weeks 24 and 36 | Change at Week 24 | 0.69 Log Transformed Milligrams | Standard Deviation 1.822 |
| Dupilumab | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Weeks 24 and 36 | Change at Week 36 | 3.38 Log Transformed Milligrams | Standard Deviation 3.096 |
Secondary
Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36
The titrated SPT is the skin testing for atopic response at different concentrations of peanut extract with saline as negative control and histamine as positive controls. Wheal size induced by peanut extract at each concentration was calculated as average of largest diameter and perpendicular midpoint diameter. The AUC for titrated SPT was calculated using the mean wheal diameter versus the concentration at which the wheal diameter was measured, which was then normalized to concentration. Change from baseline in titrated SPT as measured by average wheal size AUC after peanut allergen stimulation at different concentrations at Weeks 4, 12, 24, and 36 was reported.
Time frame: Weeks 4, 12, 24, and 36
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36 | Change at Week 4 | -0.633 millimeter (mm) | Standard Deviation 2.0604 |
| Dupilumab | Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36 | Change at Week 12 | -0.174 millimeter (mm) | Standard Deviation 2.0618 |
| Dupilumab | Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36 | Change at Week 24 | -0.232 millimeter (mm) | Standard Deviation 2.061 |
| Dupilumab | Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36 | Change at Week 36 | -0.364 millimeter (mm) | Standard Deviation 2.1419 |
Secondary
Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 24
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed a DBPCFC with at least 1044 mg (cumulative) peanut protein at Week 24 was reported.
Time frame: At Week 24
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 24 | 0.0 Percentage of Participants |
Secondary
Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 36
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC.
Time frame: At Week 36
Population: A subset of the SAF that included only participants who passed the DBPCFC of at least 444 mg (cumulative) at Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 36 | 50.0 Percentage of Participants |
Secondary
Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 24
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab who passed a DBPCFC with at least 2044 mg (cumulative) peanut protein at Week 24 was reported.
Time frame: At Week 24
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 24 | 0.0 Percentage of Participants |
Secondary
Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 36
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC.
Time frame: At Week 36
Population: A subset of the SAF that included only participants who passed the DBPCFC of at least 444 mg (cumulative) at Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 36 | 0.0 Percentage of Participants |
Secondary
Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 36
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC.
Time frame: At Week 36
Population: A subset of the SAF that included only participants who passed the DBPCFC of at least 444 mg (cumulative) at Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 36 | 50.0 Percentage of Participants |
Secondary
Percentage of Participants Who Used Epinephrine as a Rescue Medication During the DBPCFC at Week 24
Percentage of participants who used Epinephrine as a rescue medication during the DBPCFC at Week 24 was reported.
Time frame: At Week 24
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Who Used Epinephrine as a Rescue Medication During the DBPCFC at Week 24 | 41.7 Percentage of Participants |
Secondary
Percentage of Participants With Grade 2 or Above Allergic Reactions During the DBPCFC at Week 24
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Percentage of participants with Grade 2 (Moderate) or above allergic reactions during the DBPCFC at Week 24 was reported.
Time frame: At Week 24
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants With Grade 2 or Above Allergic Reactions During the DBPCFC at Week 24 | 33.3 Percentage of Participants |
Secondary
Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36
Percent change from baseline in sIgE at Weeks 4, 8, 12, 16, 24, and 36 was reported.
Time frame: Weeks 4, 8, 12, 16, 24, and 36
Population: The SAF included all participants who received dupilumab.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dupilumab | Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change at Week 4 | -7.86 Percent Change |
| Dupilumab | Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change at Week 8 | -21.03 Percent Change |
| Dupilumab | Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change at Week 12 | -32.10 Percent Change |
| Dupilumab | Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change at Week 16 | -32.22 Percent Change |
| Dupilumab | Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change at Week 24 | -49.25 Percent Change |
| Dupilumab | Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change at Week 36 | -58.43 Percent Change |