Trial Outcomes & Findings for Study in Pediatric Subjects With Peanut Allergy to Evaluate Efficacy and Safety of Dupilumab as Adjunct to AR101 (Peanut Oral Immunotherapy) (NCT NCT03682770)

Last Updated: 2024-02-07

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

148 participants

Primary outcome timeframe

At Visit 16 (Week 28 to 40)

Results posted on

2024-02-07

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Pre-AR101 Dosing Period: Placebo-matched Dupilumab Participants received placebo-matched dupilumab	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	AR101 Up-dosing Period: Placebo + AR101 Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules	AR101 Maintenance Period: Placebo-matched Dupilumab + AR101 Continued Participants who received placebo-matched dupilumab + AR101 in the up-dosing period continued in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101 Continued Participants who received dupilumab + AR101 in up-dosing period continued to receive dupilumab + AR101 in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101/Placebo-matched Dupilumab + AR101 Participants who received dupilumab + AR101 in the up-dosing period switched to placebo-matched dupilumab + AR101 in the maintenance period
Pre-AR101 Dosing Period (Day 1 - Week 4) STARTED	50	98	0	0	0	0	0
Pre-AR101 Dosing Period (Day 1 - Week 4) COMPLETED	49	96	0	0	0	0	0
Pre-AR101 Dosing Period (Day 1 - Week 4) NOT COMPLETED	1	2	0	0	0	0	0
AR101 Up-dosing Period (Week 28-40) STARTED	0	0	49	96	0	0	0
AR101 Up-dosing Period (Week 28-40) COMPLETED	0	0	39	88	0	0	0
AR101 Up-dosing Period (Week 28-40) NOT COMPLETED	0	0	10	8	0	0	0
AR101 Maintenance Period: (Week 52-64) STARTED	0	0	0	0	40	44	44
AR101 Maintenance Period: (Week 52-64) Randomized and Treated	0	0	0	0	40	43	42
AR101 Maintenance Period: (Week 52-64) COMPLETED	0	0	0	0	36	41	41
AR101 Maintenance Period: (Week 52-64) NOT COMPLETED	0	0	0	0	4	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Pre-AR101 Dosing Period: Placebo-matched Dupilumab Participants received placebo-matched dupilumab	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	AR101 Up-dosing Period: Placebo + AR101 Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules	AR101 Maintenance Period: Placebo-matched Dupilumab + AR101 Continued Participants who received placebo-matched dupilumab + AR101 in the up-dosing period continued in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101 Continued Participants who received dupilumab + AR101 in up-dosing period continued to receive dupilumab + AR101 in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101/Placebo-matched Dupilumab + AR101 Participants who received dupilumab + AR101 in the up-dosing period switched to placebo-matched dupilumab + AR101 in the maintenance period
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
AR101 Up-dosing Period (Week 28-40) Withdrawal by Subject	0	0	7	3	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) Investigator/Sponsor decision	0	0	1	2	0	0	0
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) Other	0	0	0	2	0	0	0
AR101 Maintenance Period: (Week 52-64) Withdrawal by Subject	0	0	0	0	3	1	1
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

Baseline Characteristics

Study in Pediatric Subjects With Peanut Allergy to Evaluate Efficacy and Safety of Dupilumab as Adjunct to AR101 (Peanut Oral Immunotherapy)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pre-AR101 Dosing Period: Placebo-matched Dupilumab n=50 Participants Participants received placebo-matched dupilumab	Pre-AR101 Dosing Period: Dupilumab n=98 Participants 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	Total n=148 Participants Total of all reporting groups
Age, Continuous	10.9 years STANDARD_DEVIATION 3.00 • n=5 Participants	11.3 years STANDARD_DEVIATION 3.12 • n=7 Participants	11.1 years STANDARD_DEVIATION 3.08 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	38 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	60 Participants n=7 Participants	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	87 Participants n=7 Participants	132 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White	40 participants n=5 Participants	70 participants n=7 Participants	110 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Asian	7 participants n=5 Participants	18 participants n=7 Participants	25 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=39 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=84 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval 21.204 to 52.82	55.95 Percentage of participants Interval 44.695 to 66.778

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=39 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=84 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 0.270	4.45 Log Transformed Milligrams Standard Error 0.205

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=39 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=84 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval 60.674 to 88.866	89.29 Percentage of participants Interval 80.633 to 94.982

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=39 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=84 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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	167.5 Days Standard Deviation 32.01

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=40 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=44 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval 31.512 to 63.872	56.82 Percentage of participants Interval 41.034 to 71.651

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=40 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=44 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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	4.56 Log Transformed Milligrams Standard Error 0.250

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=40 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=44 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval 31.512 to 63.872	45.45 Percentage of participants Interval 30.391 to 61.153

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=40 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=44 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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	4.14 Log Transformed Milligrams Standard Error 0.244

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=39 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=84 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval 3.3 to 82.2	-60.6 Percent change Interval -68.1 to -50.5

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=29 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=36 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval -73.3 to 98.5	-73.7 Percent change Interval -91.7 to -52.5

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	AR101 Up-dosing Period: Placebo + AR101 n=29 Participants Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=36 Participants Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules
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 Interval -84.6 to 94.7	-73.9 Percent change Interval -91.6 to -45.5

Adverse Events

Pre-AR101 Dosing Period: Placebo-matched Dupilumab

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Pre-AR101 Dosing Period: Dupilumab

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

AR101 Up-dosing Period: Placebo + AR101

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

AR101 Up-dosing Period: Dupilumab + AR101

Serious events: 0 serious events

Other events: 47 other events

Deaths: 0 deaths

AR101 Maintenance Period: Placebo-matched Dupilumab + AR101 Continued

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

AR101 Maintenance Period: Dupilumab + AR101 Continued

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

AR101 Maintenance Period: Dupilumab + AR101/Placebo-matched Dupilumab + AR101

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pre-AR101 Dosing Period: Placebo-matched Dupilumab n=50 participants at risk Participants received placebo-matched dupilumab	Pre-AR101 Dosing Period: Dupilumab n=98 participants at risk 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	AR101 Up-dosing Period: Placebo + AR101 n=49 participants at risk Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=96 participants at risk Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules	AR101 Maintenance Period: Placebo-matched Dupilumab + AR101 Continued n=40 participants at risk Participants who received placebo-matched dupilumab + AR101 in the up-dosing period continued in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101 Continued n=42 participants at risk Participants who received dupilumab + AR101 in up-dosing period continued to receive dupilumab + AR101 in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101/Placebo-matched Dupilumab + AR101 n=43 participants at risk Participants who received dupilumab + AR101 in the up-dosing period switched to placebo-matched dupilumab + AR101 in the maintenance period
Infections and infestations Appendicitis	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	0.00% 0/49 • From first dose of study drug up to Week 76	0.00% 0/96 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76

Other adverse events

Other adverse events
Measure	Pre-AR101 Dosing Period: Placebo-matched Dupilumab n=50 participants at risk Participants received placebo-matched dupilumab	Pre-AR101 Dosing Period: Dupilumab n=98 participants at risk 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	AR101 Up-dosing Period: Placebo + AR101 n=49 participants at risk Participants who received placebo-matched dupilumab in the pre-AR101 dosing period received placebo in combination with a gradual up-dosing of AR101 oral capsules	AR101 Up-dosing Period: Dupilumab + AR101 n=96 participants at risk Participants who received dupilumab in the pre-AR101 dosing period received dupilumab during the up-dosing period in combination with a gradual up-dosing of AR101 oral capsules	AR101 Maintenance Period: Placebo-matched Dupilumab + AR101 Continued n=40 participants at risk Participants who received placebo-matched dupilumab + AR101 in the up-dosing period continued in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101 Continued n=42 participants at risk Participants who received dupilumab + AR101 in up-dosing period continued to receive dupilumab + AR101 in the maintenance period	AR101 Maintenance Period: Dupilumab + AR101/Placebo-matched Dupilumab + AR101 n=43 participants at risk Participants who received dupilumab + AR101 in the up-dosing period switched to placebo-matched dupilumab + AR101 in the maintenance period
Infections and infestations Upper respiratory tract infection	10.0% 5/50 • Number of events 5 • From first dose of study drug up to Week 76	2.0% 2/98 • Number of events 2 • From first dose of study drug up to Week 76	14.3% 7/49 • Number of events 9 • From first dose of study drug up to Week 76	16.7% 16/96 • Number of events 21 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 2 • From first dose of study drug up to Week 76	11.9% 5/42 • Number of events 8 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Infections and infestations Viral infection	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 3 • From first dose of study drug up to Week 76	7.3% 7/96 • Number of events 13 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	4.7% 2/43 • Number of events 2 • From first dose of study drug up to Week 76
Infections and infestations Viral upper respiratory tract infection	2.0% 1/50 • Number of events 1 • From first dose of study drug up to Week 76	2.0% 2/98 • Number of events 2 • From first dose of study drug up to Week 76	0.00% 0/49 • From first dose of study drug up to Week 76	6.2% 6/96 • Number of events 7 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Infections and infestations Gastroenteritis viral	2.0% 1/50 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 3 • From first dose of study drug up to Week 76	2.1% 2/96 • Number of events 4 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	2.3% 1/43 • Number of events 1 • From first dose of study drug up to Week 76
Infections and infestations Otitis media	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 3 • From first dose of study drug up to Week 76	1.0% 1/96 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	2.3% 1/43 • Number of events 1 • From first dose of study drug up to Week 76
Gastrointestinal disorders Abdominal pain	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	10.2% 5/49 • Number of events 10 • From first dose of study drug up to Week 76	9.4% 9/96 • Number of events 12 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 1 • From first dose of study drug up to Week 76	9.5% 4/42 • Number of events 9 • From first dose of study drug up to Week 76	7.0% 3/43 • Number of events 5 • From first dose of study drug up to Week 76
Gastrointestinal disorders Abdominal pain upper	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 2 • From first dose of study drug up to Week 76	4.1% 2/49 • Number of events 5 • From first dose of study drug up to Week 76	8.3% 8/96 • Number of events 12 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 1 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	4.7% 2/43 • Number of events 3 • From first dose of study drug up to Week 76
Gastrointestinal disorders Nausea	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 7 • From first dose of study drug up to Week 76	6.2% 6/96 • Number of events 7 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	4.8% 2/42 • Number of events 2 • From first dose of study drug up to Week 76	4.7% 2/43 • Number of events 2 • From first dose of study drug up to Week 76
Gastrointestinal disorders Vomiting	0.00% 0/50 • From first dose of study drug up to Week 76	2.0% 2/98 • Number of events 2 • From first dose of study drug up to Week 76	16.3% 8/49 • Number of events 11 • From first dose of study drug up to Week 76	5.2% 5/96 • Number of events 6 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 1 • From first dose of study drug up to Week 76	4.8% 2/42 • Number of events 3 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Gastrointestinal disorders Diarrhoea	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	10.2% 5/49 • Number of events 6 • From first dose of study drug up to Week 76	5.2% 5/96 • Number of events 7 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	7.1% 3/42 • Number of events 5 • From first dose of study drug up to Week 76	2.3% 1/43 • Number of events 2 • From first dose of study drug up to Week 76
Gastrointestinal disorders Oral pruritus	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 4 • From first dose of study drug up to Week 76	4.2% 4/96 • Number of events 8 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 1 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 1/50 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 3 • From first dose of study drug up to Week 76	7.3% 7/96 • Number of events 11 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	10.2% 5/49 • Number of events 6 • From first dose of study drug up to Week 76	4.2% 4/96 • Number of events 5 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Respiratory, thoracic and mediastinal disorders Asthma	2.0% 1/50 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	8.2% 4/49 • Number of events 7 • From first dose of study drug up to Week 76	2.1% 2/96 • Number of events 2 • From first dose of study drug up to Week 76	10.0% 4/40 • Number of events 4 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	2.3% 1/43 • Number of events 1 • From first dose of study drug up to Week 76
General disorders Injection site reaction	0.00% 0/50 • From first dose of study drug up to Week 76	5.1% 5/98 • Number of events 9 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 13 • From first dose of study drug up to Week 76	6.2% 6/96 • Number of events 14 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 2 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
General disorders Injection site urticaria	4.0% 2/50 • Number of events 2 • From first dose of study drug up to Week 76	5.1% 5/98 • Number of events 7 • From first dose of study drug up to Week 76	4.1% 2/49 • Number of events 9 • From first dose of study drug up to Week 76	5.2% 5/96 • Number of events 14 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Immune system disorders Anaphylactic reaction	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	4.1% 2/49 • Number of events 2 • From first dose of study drug up to Week 76	5.2% 5/96 • Number of events 6 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	4.8% 2/42 • Number of events 3 • From first dose of study drug up to Week 76	7.0% 3/43 • Number of events 3 • From first dose of study drug up to Week 76
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	4.1% 2/49 • Number of events 2 • From first dose of study drug up to Week 76	4.2% 4/96 • Number of events 6 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	7.1% 3/42 • Number of events 4 • From first dose of study drug up to Week 76	2.3% 1/43 • Number of events 1 • From first dose of study drug up to Week 76
Skin and subcutaneous tissue disorders Rash	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	8.2% 4/49 • Number of events 4 • From first dose of study drug up to Week 76	4.2% 4/96 • Number of events 4 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 2 • From first dose of study drug up to Week 76	4.8% 2/42 • Number of events 2 • From first dose of study drug up to Week 76	7.0% 3/43 • Number of events 4 • From first dose of study drug up to Week 76
Nervous system disorders Headache	2.0% 1/50 • Number of events 1 • From first dose of study drug up to Week 76	2.0% 2/98 • Number of events 3 • From first dose of study drug up to Week 76	8.2% 4/49 • Number of events 8 • From first dose of study drug up to Week 76	5.2% 5/96 • Number of events 9 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 6 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	4.7% 2/43 • Number of events 2 • From first dose of study drug up to Week 76
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	0.00% 0/49 • From first dose of study drug up to Week 76	4.2% 4/96 • Number of events 4 • From first dose of study drug up to Week 76	5.0% 2/40 • Number of events 2 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	2.0% 1/50 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 3 • From first dose of study drug up to Week 76	3.1% 3/96 • Number of events 3 • From first dose of study drug up to Week 76	7.5% 3/40 • Number of events 3 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	4.7% 2/43 • Number of events 2 • From first dose of study drug up to Week 76
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	4.1% 2/49 • Number of events 2 • From first dose of study drug up to Week 76	2.1% 2/96 • Number of events 2 • From first dose of study drug up to Week 76	5.0% 2/40 • Number of events 2 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	6.1% 3/49 • Number of events 6 • From first dose of study drug up to Week 76	3.1% 3/96 • Number of events 7 • From first dose of study drug up to Week 76	0.00% 0/40 • From first dose of study drug up to Week 76	2.4% 1/42 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76
Skin and subcutaneous tissue disorders Eczema	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	0.00% 0/49 • From first dose of study drug up to Week 76	2.1% 2/96 • Number of events 3 • From first dose of study drug up to Week 76	2.5% 1/40 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	7.0% 3/43 • Number of events 3 • From first dose of study drug up to Week 76
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/50 • From first dose of study drug up to Week 76	0.00% 0/98 • From first dose of study drug up to Week 76	2.0% 1/49 • Number of events 2 • From first dose of study drug up to Week 76	1.0% 1/96 • Number of events 1 • From first dose of study drug up to Week 76	5.0% 2/40 • Number of events 2 • From first dose of study drug up to Week 76	4.8% 2/42 • Number of events 2 • From first dose of study drug up to Week 76	2.3% 1/43 • Number of events 1 • From first dose of study drug up to Week 76
Psychiatric disorders Anxiety	0.00% 0/50 • From first dose of study drug up to Week 76	1.0% 1/98 • Number of events 1 • From first dose of study drug up to Week 76	0.00% 0/49 • From first dose of study drug up to Week 76	0.00% 0/96 • From first dose of study drug up to Week 76	5.0% 2/40 • Number of events 2 • From first dose of study drug up to Week 76	0.00% 0/42 • From first dose of study drug up to Week 76	0.00% 0/43 • From first dose of study drug up to Week 76

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc

Phone: 844-734-6643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER