Peanut Allergy
Conditions
Brief summary
Primary objective is to assess whether dupilumab as adjunct to AR101 compared to placebo improves desensitization at the completion of up-dosing, defined as an increase in the proportion of participants who pass a post up-dosing double-blind placebo-controlled food challenge (DBPCFC) at visit 16. Secondary objectives are: * To assess whether dupilumab as adjunct to AR101 compared to placebo improves desensitization at the completion of up-dosing, defined as an increase in the cumulative tolerated dose (log transformed) of peanut protein during a post up-dosing DBPCFC at visit 16 * To assess whether dupilumab as (indefinite \[continuously\]) adjunct to AR101 compared to placebo maintains desensitization, defined as an increase in the proportion of participants who pass a post maintenance DBPCFC at visit 22 * To assess whether dupilumab as (limited \[previously\]) adjunct to AR101 compared to placebo maintains desensitization, defined as an increase in the proportion of participants who pass a post maintenance DBPCFC at visit 22 * To evaluate the safety and tolerability of dupilumab as adjunct to AR101 compared to placebo * To assess the effect of dupilumab (compared to placebo) as adjunct to AR101 on the change in peanut-specific Immunoglobulin E (sIgE), Immunoglobulin G (IgG), Immunoglobulin G4 (IgG4), and peanut-specific IgG4/IgE ratio * To assess if dupilumab increases the tolerability of AR101 as measured by the daily symptoms (electronic diary \[e-diary\]) during the up-dosing phase
Interventions
DRUGDupilumab
Dupilumab will be administered subcutaneously (SC) in a single-use, pre-filled glass syringe every two weeks (Q2W)
Placebo matching dupilumab is prepared in the same formulation without the addition of protein
DRUGAR101
AR101 will be provided in dose-escalating capsules and then sachets during maintenance phase
Sponsors
Sanofi
Aimmune Therapeutics, Inc.
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Experience dose-limiting symptoms at or before the challenge dose of peanut protein on screening and not experiencing dose-limiting symptoms to placebo as defined in the protocol * Serum Immunoglobulin E (IgE) to peanut of ≥10 kUA/L and/or a skin prick test (SPT) to peanut ≥8 mm compared to a negative control * Participants/legal guardians must be trained on the proper use of the epinephrine autoinjector device to be allowed to enroll in the study * Participants 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
* History of other chronic disease (other than asthma, Atopic Dermatitis (AD), or allergic rhinitis) requiring therapy (eg, heart disease, diabetes, hypertension) that would represent a risk to participant's health or safety in this study or ability to comply with study protocol * History of frequent or recent severe, life-threatening episode of anaphylaxis or anaphylactic shock * History of eosinophilic Gastrointestinal (GI) disease * Asthma at time of enrollment with any of the following: * Forced Expiratory Volume 1 Second (FEV1) \<80% of predicted or ratio of FEV1 to forced vital capacity (FEV1/FVC) \<75% of predicted with or without controller medications * Inhaled corticosteroids (ICS) dosing of daily fluticasone (or equivalent ICS based on NHLBI dosing chart) * One hospitalization in the past year for asthma * Emergency room visit for asthma within 6 months prior to screening * Use of systemic corticosteroids within 2 months prior to screening * Use of other forms of allergen immunotherapy or immunomodulatory therapy within 3 months prior to screening * Use of any agents known or likely to interact with epinephrine (eg, beta-blockers, angiotensin converting enzyme-inhibitors, tri-cyclic antidepressants, or other drugs), within 3 weeks prior to screening * Allergy to oat (placebo in DBPCFC) Note: Other protocol Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Up-dosing Double-blind, Placebo-controlled Food Challenge (DBPCFC) With 2044 mg (Cumulative) Peanut Protein at Visit 16 (Week 28 to 40) | At Visit 16 (Week 28 to 40) | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. 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 plus AR101 vs placebo plus AR101 who passed a post up-dosing DBPCFC with 2044 mg (Cumulative) peanut protein at Visit 16 (Week 28 to 40) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Reached the 300 mg/Day Dose of AR101 by Visit 16 (Week 28 to 40) | At Visit 16 (Week 28 to 40) | Percentage of participants treated with dupilumab plus AR101 vs placebo plus AR101 who reached the 300 mg/day dose of AR101 by Visit 16 (Week 28 to 40) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40). |
| Time From Randomization to the First Time When Participants Reached the 300 mg/Day Dose of AR101 During the Up-dosing Treatment Phase by Visit 16 (Week 28 to 40) | At Visit 16 (Week 28 to 40) | Time (in days) from randomization to the first time when participants reached the 300 mg/day dose of AR101 during the up-dosing treatment phase by Visit 16 (Week 28 to 40) was reported. If participants did not reach the 300 mg/day dose of AR101 during the 28-week treatment period, they were censored at the date of their last visit during pre-AR101 dosing and AR101 up-dosing treatment period. Analysis was performed using Kaplan-Meier Estimated method. |
| Percentage of Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64) | At Visit 22 (Week 52 to 64) | Symptoms considered to be allergic were graded using the CoFAR Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. 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 (continuously) treated with dupilumab plus AR101 vs placebo plus AR101 who passed a post maintenance DBPCFC with 2044 mg (cumulative) peanut protein at Visit 22 (Week 52 to 64) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64). |
| Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 | Baseline, Visit 22 (Week 52 to 64) | Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Visit 22 (Week 52 to 64) in participants (continuously) treated with dupilumab plus AR101 vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 52 to Week 64). |
| Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 16 (Week 28 to 40) in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 | Baseline, Visit 16 (Week 28 to 40) | Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Visit 16 (Week 28 to 40) in participants treated with dupilumab plus AR101 vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 28 to Week 40). |
| Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 | Baseline, Visit 22 (Week 52 to 64) | Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Visit 22 (Week 52 to 64) in participants (previously) treated with dupilumab plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 52 to Week 64). |
| Percent Change From Baseline in Peanut-specific IgE in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 16 (Week 28 to 40) | Baseline up to Visit 16 (Weeks 28 to 40) | Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 16 (Week 28 to 40) was reported. Analysis was performed using Last observation carried forward (LOCF) method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40). |
| Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 22 (Week 52 to 64) | Baseline up to Visit 22 (Week 52 to 64) | Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 22 (Week 52 to 64) was reported. Analysis was performed using LOCF method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64). |
| Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 25 (Weeks 64 to 76) | Baseline up to Visit 25 (Weeks 64 to 76) | Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 25 (Week 64 to 76) was reported. Analysis was performed using LOCF method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 64 to Week 76). |
| Percentage of Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64) | At Visit 22 (Week 52 to 64) | Symptoms considered to be allergic were graded using the CoFAR Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. 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 (previously) treated with dupilumab plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 who pass a post maintenance DBPCFC with 2044 mg (cumulative) peanut protein at Visit 22 (Week 52 to 64) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64). |
Countries
United States
Participant flow
Pre-assignment details
A total of 232 participants were screened; 148 participants were randomized. Of the 84 not randomized, 53 did not meet inclusion/exclusion criteria and 13 withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Pre-AR101 Dosing Period: Placebo-matched Dupilumab Participants received placebo-matched dupilumab | 50 |
| Pre-AR101 Dosing Period: Dupilumab Participants of ≥60 kilograms (kg) body weight (BW) received dupilumab 300 milligrams (mg) subcutaneously (SC) every 2 weeks (Q2W); participants of ≥ 30kg to \< 60kg BW received dupilumab 200 mg SC Q2W; participants of \<30kg BW received dupilumab 100 mg SC Q2W | 98 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| AR101 Maintenance Period: (Week 52-64) | Investigator/Sponsor decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| AR101 Maintenance Period: (Week 52-64) | Other | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| AR101 Maintenance Period: (Week 52-64) | Randomized, but not treated | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| AR101 Maintenance Period: (Week 52-64) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 1 | 1 |
| AR101 Up-dosing Period (Week 28-40) | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| AR101 Up-dosing Period (Week 28-40) | Chronic/recurrent GI AEs/Symptoms | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| AR101 Up-dosing Period (Week 28-40) | Investigator/Sponsor decision | 0 | 0 | 1 | 2 | 0 | 0 | 0 |
| AR101 Up-dosing Period (Week 28-40) | Other | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| AR101 Up-dosing Period (Week 28-40) | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| AR101 Up-dosing Period (Week 28-40) | Withdrawal by Subject | 0 | 0 | 7 | 3 | 0 | 0 | 0 |
| Pre-AR101 Dosing Period (Day 1 - Week 4) | Sponsor decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Pre-AR101 Dosing Period (Day 1 - Week 4) | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Pre-AR101 Dosing Period: Placebo-matched Dupilumab | Pre-AR101 Dosing Period: Dupilumab |
|---|---|---|---|
| Age, Continuous | 11.1 years STANDARD_DEVIATION 3.08 | 10.9 years STANDARD_DEVIATION 3 | 11.3 years STANDARD_DEVIATION 3.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 45 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 25 participants | 7 participants | 18 participants |
| Race/Ethnicity, Customized Black or African American | 4 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 8 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized White | 110 participants | 40 participants | 70 participants |
| Sex: Female, Male Female | 56 Participants | 18 Participants | 38 Participants |
| Sex: Female, Male Male | 92 Participants | 32 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 98 | 0 / 49 | 0 / 96 | 0 / 40 | 0 / 42 | 0 / 43 |
| other Total, other adverse events | 12 / 50 | 23 / 98 | 34 / 49 | 47 / 96 | 13 / 40 | 17 / 42 | 15 / 43 |
| serious Total, serious adverse events | 0 / 50 | 0 / 98 | 0 / 49 | 0 / 96 | 0 / 40 | 1 / 42 | 0 / 43 |
Outcome results
Primary
Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Up-dosing Double-blind, Placebo-controlled Food Challenge (DBPCFC) With 2044 mg (Cumulative) Peanut Protein at Visit 16 (Week 28 to 40)
Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. 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 plus AR101 vs placebo plus AR101 who passed a post up-dosing DBPCFC with 2044 mg (Cumulative) peanut protein at Visit 16 (Week 28 to 40) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).
Time frame: At Visit 16 (Week 28 to 40)
Population: Modified full analysis set (mFAS) included all participants in the full analysis set (FAS) who underwent biweekly in-clinic up-dosing as described/specified in the protocol and underwent the post up-dosing DBPCFC at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Up-dosing Period: Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Up-dosing Double-blind, Placebo-controlled Food Challenge (DBPCFC) With 2044 mg (Cumulative) Peanut Protein at Visit 16 (Week 28 to 40) | 35.90 Percentage of participants |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Up-dosing Double-blind, Placebo-controlled Food Challenge (DBPCFC) With 2044 mg (Cumulative) Peanut Protein at Visit 16 (Week 28 to 40) | 55.95 Percentage of participants |
p-value: 0.04295% CI: [1.266, 39.189]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 16 (Week 28 to 40) in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101
Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Visit 16 (Week 28 to 40) in participants treated with dupilumab plus AR101 vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 28 to Week 40).
Time frame: Baseline, Visit 16 (Week 28 to 40)
Population: mFAS included all participants in the FAS who underwent biweekly in-clinic up-dosing as described/specified in the protocol and underwent the post up-dosing DBPCFC at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Up-dosing Period: Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 16 (Week 28 to 40) in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 | 3.78 Log Transformed Milligrams | Standard Error 0.27 |
| AR101 Up-dosing Period: Dupilumab + AR101 | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 16 (Week 28 to 40) in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 | 4.45 Log Transformed Milligrams | Standard Error 0.205 |
p-value: 0.0495% CI: [0.031, 1.305]ANCOVA
Secondary
Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101
Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Visit 22 (Week 52 to 64) in participants (continuously) treated with dupilumab plus AR101 vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 52 to Week 64).
Time frame: Baseline, Visit 22 (Week 52 to 64)
Population: FAS-maintenance (a subset of FAS) included participants in the FAS who achieved 300 mg/day AR101 for at least 2 weeks in the up-dosing phase and re-randomized based on the treatment allocated by the IWRS at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Maintenance Period: Continuously on Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 | 4.19 Log Transformed Milligrams | Standard Error 0.245 |
| AR101 Up-dosing Period: Dupilumab + AR101 | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 | 4.56 Log Transformed Milligrams | Standard Error 0.25 |
p-value: 0.262895% CI: [-0.281, 1.029]ANCOVA
Secondary
Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101
Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Visit 22 (Week 52 to 64) in participants (previously) treated with dupilumab plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 52 to Week 64).
Time frame: Baseline, Visit 22 (Week 52 to 64)
Population: FAS-maintenance (a subset of FAS) included participants in the FAS who achieved 300 mg/day AR101 for at least 2 weeks in the up-dosing phase and re-randomized based on the treatment allocated by the IWRS at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Maintenance Period: Dupilumab + AR101/Placebo +AR101 vs Placebo + AR101.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 | 4.19 Log Transformed Milligrams | Standard Error 0.245 |
| AR101 Up-dosing Period: Dupilumab + AR101 | Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 | 4.14 Log Transformed Milligrams | Standard Error 0.244 |
p-value: 0.880595% CI: [-0.699, 0.599]ANCOVA
Secondary
Percentage of Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64)
Symptoms considered to be allergic were graded using the CoFAR Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. 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 (continuously) treated with dupilumab plus AR101 vs placebo plus AR101 who passed a post maintenance DBPCFC with 2044 mg (cumulative) peanut protein at Visit 22 (Week 52 to 64) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64).
Time frame: At Visit 22 (Week 52 to 64)
Population: FAS-maintenance (a subset of FAS) included participants in the FAS who achieved 300 mg/day AR101 for at least 2 weeks in the up-dosing phase and re-randomized based on the treatment allocated by the IWRS at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Maintenance Period: Continuously on Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percentage of Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64) | 47.50 Percentage of participants |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percentage of Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64) | 56.82 Percentage of participants |
p-value: 0.35395% CI: [-11.668, 32.474]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64)
Symptoms considered to be allergic were graded using the CoFAR Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. 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 (previously) treated with dupilumab plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 who pass a post maintenance DBPCFC with 2044 mg (cumulative) peanut protein at Visit 22 (Week 52 to 64) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64).
Time frame: At Visit 22 (Week 52 to 64)
Population: FAS-maintenance (a subset of FAS) included participants in the FAS who achieved 300 mg/day AR101 for at least 2 weeks in the up-dosing phase and re-randomized based on the treatment allocated by the IWRS at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Maintenance Period: Dupilumab + AR101/Placebo +AR101 vs Placebo + AR101.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percentage of Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64) | 47.50 Percentage of participants |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percentage of Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64) | 45.45 Percentage of participants |
p-value: 0.81495% CI: [-25.004, 20.282]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Reached the 300 mg/Day Dose of AR101 by Visit 16 (Week 28 to 40)
Percentage of participants treated with dupilumab plus AR101 vs placebo plus AR101 who reached the 300 mg/day dose of AR101 by Visit 16 (Week 28 to 40) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).
Time frame: At Visit 16 (Week 28 to 40)
Population: mFAS included all participants in the FAS who underwent biweekly in-clinic up-dosing as described/specified in the protocol and underwent the post up-dosing DBPCFC at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Up-dosing Period: Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Reached the 300 mg/Day Dose of AR101 by Visit 16 (Week 28 to 40) | 76.92 Percentage of participants |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Reached the 300 mg/Day Dose of AR101 by Visit 16 (Week 28 to 40) | 89.29 Percentage of participants |
p-value: 0.080695% CI: [-3.612, 27.44]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 22 (Week 52 to 64)
Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 22 (Week 52 to 64) was reported. Analysis was performed using LOCF method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64).
Time frame: Baseline up to Visit 22 (Week 52 to 64)
Population: mFAS-maintenance (a subset of mFAS) included participants in the mFAS who achieved 300 mg/day AR101 for at-least 2 weeks in the up-dosing phase and re-randomized based on the treatment allocated by the IWRS at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Maintenance Period: Continuously on Dupilumab Plus AR101 vs Placebo Plus AR101.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 22 (Week 52 to 64) | 10.1 Percent change |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 22 (Week 52 to 64) | -73.7 Percent change |
p-value: <0.000195% CI: [-99.47, -73.91]ANCOVA
Secondary
Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 25 (Weeks 64 to 76)
Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 25 (Week 64 to 76) was reported. Analysis was performed using LOCF method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 64 to Week 76).
Time frame: Baseline up to Visit 25 (Weeks 64 to 76)
Population: mFAS-maintenance (a subset of mFAS) included participants in the mFAS who achieved 300 mg/day AR101 for at-least 2 weeks in the up-dosing phase and re-randomized based on the treatment allocated by the IWRS at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Maintenance Period: Continuously on Dupilumab Plus AR101 vs Placebo Plus AR101.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 25 (Weeks 64 to 76) | -7.2 Percent change |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 25 (Weeks 64 to 76) | -73.9 Percent change |
p-value: <0.000195% CI: [-86.71, -56.4]ANCOVA
Secondary
Percent Change From Baseline in Peanut-specific IgE in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 16 (Week 28 to 40)
Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 16 (Week 28 to 40) was reported. Analysis was performed using Last observation carried forward (LOCF) method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).
Time frame: Baseline up to Visit 16 (Weeks 28 to 40)
Population: mFAS included all participants in the FAS who underwent biweekly in-clinic up-dosing as described/specified in the protocol and underwent the post up-dosing DBPCFC at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Up-dosing Period: Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Percent Change From Baseline in Peanut-specific IgE in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 16 (Week 28 to 40) | 29.9 Percent change |
| AR101 Up-dosing Period: Dupilumab + AR101 | Percent Change From Baseline in Peanut-specific IgE in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 16 (Week 28 to 40) | -60.6 Percent change |
Secondary
Time From Randomization to the First Time When Participants Reached the 300 mg/Day Dose of AR101 During the Up-dosing Treatment Phase by Visit 16 (Week 28 to 40)
Time (in days) from randomization to the first time when participants reached the 300 mg/day dose of AR101 during the up-dosing treatment phase by Visit 16 (Week 28 to 40) was reported. If participants did not reach the 300 mg/day dose of AR101 during the 28-week treatment period, they were censored at the date of their last visit during pre-AR101 dosing and AR101 up-dosing treatment period. Analysis was performed using Kaplan-Meier Estimated method.
Time frame: At Visit 16 (Week 28 to 40)
Population: mFAS included all participants in the FAS who underwent biweekly in-clinic up-dosing as described/specified in the protocol and underwent the post up-dosing DBPCFC at Visit 16 (Weeks 28 to 40). Data were planned to be reported and analyzed only for AR101 Up-dosing Period: Dupilumab plus AR101 vs Placebo plus AR101.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AR101 Up-dosing Period: Placebo + AR101 | Time From Randomization to the First Time When Participants Reached the 300 mg/Day Dose of AR101 During the Up-dosing Treatment Phase by Visit 16 (Week 28 to 40) | 164.6 Days | Standard Deviation 38.43 |
| AR101 Up-dosing Period: Dupilumab + AR101 | Time From Randomization to the First Time When Participants Reached the 300 mg/Day Dose of AR101 During the Up-dosing Treatment Phase by Visit 16 (Week 28 to 40) | 167.5 Days | Standard Deviation 32.01 |