Trial Outcomes & Findings for Efficacy and Safety of Viaskin Milk in Children With IgE-Mediated Cow's Milk Allergy (NCT NCT02223182)

NCT ID: NCT02223182

Last Updated: 2024-11-20

Results Overview

A treatment responder is defined as a subject who meets at least one of the following criteria: * A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins; * A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 198 participants
• Primary outcome timeframe: From baseline to Month 12 (double-blind period)
• Results posted on: 2024-11-20

Participant Flow

Participant milestones

Measure	Viaskin Milk 150 mcg One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Double-Blind Period STARTED	49	49	47	53
Double-Blind Period COMPLETED	47	45	45	52
Double-Blind Period NOT COMPLETED	2	4	2	1
Open-Label 500 Period STARTED	46	45	44	52
Open-Label 500 Period COMPLETED	40	43	32	42
Open-Label 500 Period NOT COMPLETED	6	2	12	10
Open-Label 300 Period STARTED	34	38	29	39
Open-Label 300 Period COMPLETED	23	23	14	24
Open-Label 300 Period NOT COMPLETED	11	15	15	15

Reasons for withdrawal

Measure	Viaskin Milk 150 mcg One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Double-Blind Period Adverse Event	0	2	1	0
Double-Blind Period Withdrawal by Subject	1	1	1	0
Double-Blind Period Lost to Follow-up	0	1	0	0
Double-Blind Period Non Compliance	0	0	0	1
Double-Blind Period Sponsor or Regulatory Authorities Decision	1	0	0	0
Open-Label 500 Period Adverse Event	1	0	2	1
Open-Label 500 Period Withdrawal by Subject	5	2	9	8
Open-Label 500 Period Physician Decision	0	0	0	1
Open-Label 500 Period Sponsor or Regulatory Authorities Decision	0	0	1	0
Open-Label 300 Period Withdrawal by Subject	10	13	13	15
Open-Label 300 Period Lost to Follow-up	1	0	1	0
Open-Label 300 Period Non Compliance	0	2	1	0

Baseline Characteristics

Efficacy and Safety of Viaskin Milk in Children With IgE-Mediated Cow's Milk Allergy

Baseline characteristics by cohort

Measure	Viaskin Milk 150 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.	Total n=198 Participants Total of all reporting groups
Age, Continuous	7.6 years STANDARD_DEVIATION 4.56 • n=5 Participants	7.7 years STANDARD_DEVIATION 4.34 • n=7 Participants	8.7 years STANDARD_DEVIATION 3.37 • n=5 Participants	8.1 years STANDARD_DEVIATION 4.31 • n=4 Participants	8.0 years STANDARD_DEVIATION 4.17 • n=21 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants	18 Participants n=4 Participants	74 Participants n=21 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	37 Participants n=7 Participants	27 Participants n=5 Participants	35 Participants n=4 Participants	124 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian	33 Participants n=5 Participants	28 Participants n=7 Participants	31 Participants n=5 Participants	41 Participants n=4 Participants	133 Participants n=21 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	5 Participants n=4 Participants	32 Participants n=21 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Skin Prick Test Mean wheal diameter	10.5 millimeters n=5 Participants	11.0 millimeters n=7 Participants	10.5 millimeters n=5 Participants	11.0 millimeters n=4 Participants	10.5 millimeters n=21 Participants
Cumulative Reactive Dose (CRD) of Cow's milk	144 mg of cow's milk proteins n=5 Participants	144 mg of cow's milk proteins n=7 Participants	144 mg of cow's milk proteins n=5 Participants	144 mg of cow's milk proteins n=4 Participants	144 mg of cow's milk proteins n=21 Participants
Cow's milk sIgE	58.2 kU/L n=5 Participants	67.6 kU/L n=7 Participants	64.6 kU/L n=5 Participants	61.1 kU/L n=4 Participants	61.9 kU/L n=21 Participants
Cow's milk sIgG4	14.0 mgA/L n=5 Participants	14.5 mgA/L n=7 Participants	14.0 mgA/L n=5 Participants	13.5 mgA/L n=4 Participants	14.0 mgA/L n=21 Participants

PRIMARY outcome

Timeframe: From baseline to Month 12 (double-blind period)

Population: Overall Intent-to-Treat Population

A treatment responder is defined as a subject who meets at least one of the following criteria:

• A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins;
• A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC.

Outcome measures

Measure	Viaskin Milk 150 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Percentage (%) of Subjects Who Are Treatment Responders After 12 Months of EPIT Treatment.	36.7 percent of participants	49.0 percent of participants	36.2 percent of participants	30.2 percent of participants

SECONDARY outcome

Timeframe: From baseline to Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Change in CRD from Month 0 (baseline) to Month 12 Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins.

Outcome measures

Measure	Viaskin Milk 150 mcg n=48 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=45 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=45 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=52 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Mean Cumulative Reactive Dose (CRD) of Cow's Milk Proteins.	745.1 milligrams (mg) of cow's milk proteins Standard Deviation 1197.08	1201.0 milligrams (mg) of cow's milk proteins Standard Deviation 1675.90	723.5 milligrams (mg) of cow's milk proteins Standard Deviation 1218.26	555.5 milligrams (mg) of cow's milk proteins Standard Deviation 1143.21

SECONDARY outcome

Timeframe: From baseline to Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Change in Median CRD from Month 0 (baseline) to Month 12 Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins.

Outcome measures

Measure	Viaskin Milk 150 mcg n=48 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=45 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=45 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=52 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Median Cumulative Reactive Dose (CRD) of Cow's Milk Proteins.	300 milligrams (mg) of cow's milk proteins Interval 3.0 to 1145.0	400 milligrams (mg) of cow's milk proteins Interval 100.0 to 1325.0	93 milligrams (mg) of cow's milk proteins Interval 0.0 to 1300.0	100 milligrams (mg) of cow's milk proteins Interval 0.0 to 900.0

SECONDARY outcome

Timeframe: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Median change from baseline value in levels of IgE specific to cow's milk proteins

Outcome measures

Measure	Viaskin Milk 150 mcg n=48 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in Levels of sIgE to Cow's Milk. Month 6	-5.80 kU/L Interval -37.8 to 3.8	-5.00 kU/L Interval -19.4 to 6.0	-14.40 kU/L Interval -54.95 to 2.7	-5.45 kU/L Interval -31.3 to 4.25
Change in Levels of sIgE to Cow's Milk. Month 12	-5.90 kU/L Interval -40.5 to 7.3	-2.70 kU/L Interval -16.1 to 13.3	-20.60 kU/L Interval -69.0 to -6.0	-7.70 kU/L Interval -27.7 to 1.8
Change in Levels of sIgE to Cow's Milk. Week 3	-2.43 kU/L Interval -15.75 to 8.2	2.80 kU/L Interval -3.9 to 17.1	-2.30 kU/L Interval -11.4 to 11.7	-5.40 kU/L Interval -28.0 to 1.1
Change in Levels of sIgE to Cow's Milk. Month 3	-0.70 kU/L Interval -18.2 to 11.9	3.20 kU/L Interval -10.0 to 27.0	-6.99 kU/L Interval -20.75 to 7.1	-7.20 kU/L Interval -28.5 to 0.9

SECONDARY outcome

Timeframe: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Median change from baseline value in levels of IgG4 specific to cow's milk proteins

Outcome measures

Measure	Viaskin Milk 150 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in Levels of sIgG4 to Cow's Milk. Month 12	1.20 mgA/L Interval -1.4 to 4.1	3.50 mgA/L Interval -0.5 to 10.0	1.96 mgA/L Interval -0.2 to 11.8	-1.60 mgA/L Interval -2.74 to -0.3
Change in Levels of sIgG4 to Cow's Milk. Week 3	0.24 mgA/L Interval -1.74 to 2.0	0.90 mgA/L Interval -1.3 to 2.8	0.80 mgA/L Interval -0.7 to 2.7	-0.35 mgA/L Interval -2.1 to 1.89
Change in Levels of sIgG4 to Cow's Milk. Month 3	0.90 mgA/L Interval -0.75 to 2.45	2.45 mgA/L Interval 0.1 to 4.5	2.60 mgA/L Interval -1.6 to 5.9	-0.80 mgA/L Interval -2.6 to 1.0
Change in Levels of sIgG4 to Cow's Milk. Month 6	0.10 mgA/L Interval -2.0 to 3.29	1.30 mgA/L Interval -1.2 to 5.0	1.40 mgA/L Interval -1.7 to 5.75	-1.60 mgA/L Interval -3.1 to 0.4

SECONDARY outcome

Timeframe: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Median change from baseline in levels of IgE specific to caseins, α-lactalbumin and β-lactoglobulin proteins

Outcome measures

Measure	Viaskin Milk 150 mcg n=48 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Month 3	1.15 kU/L Interval -20.35 to 11.49	-0.20 kU/L Interval -9.5 to 27.2	1.15 kU/L Interval -8.95 to 11.45	-2.46 kU/L Interval -14.7 to 10.0
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Month 6	-1.21 kU/L Interval -7.88 to 0.51	-0.53 kU/L Interval -3.93 to 3.8	-3.72 kU/L Interval -13.1 to -0.03	-0.71 kU/L Interval -4.41 to 0.6
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Month 12	-4.60 kU/L Interval -11.3 to 0.09	-1.76 kU/L Interval -9.3 to 0.05	-7.20 kU/L Interval -18.9 to -1.1	-1.20 kU/L Interval -6.5 to 0.0
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Week 3	-2.09 kU/L Interval -14.8 to 4.44	0.15 kU/L Interval -5.0 to 19.0	0.50 kU/L Interval -8.5 to 10.7	-1.80 kU/L Interval -7.75 to 6.1
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Month 6	-5.60 kU/L Interval -38.4 to 4.98	-5.80 kU/L Interval -31.0 to 6.1	-8.45 kU/L Interval -46.5 to 3.1	-2.55 kU/L Interval -17.75 to 5.5
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Month 12	-5.80 kU/L Interval -32.4 to 1.58	-2.00 kU/L Interval -29.0 to 2.9	-12.60 kU/L Interval -92.0 to -1.2	-4.45 kU/L Interval -16.3 to 7.9
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Week 3	0.07 kU/L Interval -2.18 to 2.5	-0.06 kU/L Interval -1.89 to 4.1	-0.10 kU/L Interval -3.2 to 2.6	-0.48 kU/L Interval -3.0 to 0.46
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Month 3	-0.16 kU/L Interval -4.35 to 1.31	0.18 kU/L Interval -2.9 to 5.2	-1.78 kU/L Interval -5.7 to 0.4	-1.00 kU/L Interval -2.84 to 0.9
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Week 3	-0.04 kU/L Interval -2.45 to 0.71	0.45 kU/L Interval -0.54 to 3.79	0.00 kU/L Interval -2.07 to 3.23	-0.41 kU/L Interval -3.3 to 0.33
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Month 3	-0.02 kU/L Interval -2.25 to 1.06	1.40 kU/L Interval -1.6 to 6.0	-1.17 kU/L Interval -3.46 to 0.55	-0.60 kU/L Interval -3.33 to 1.54
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Month 6	-0.29 kU/L Interval -7.4 to 0.06	-0.12 kU/L Interval -4.02 to 6.1	-3.55 kU/L Interval -11.83 to -0.02	-1.11 kU/L Interval -5.52 to 0.24
Change in Levels of sIgE to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Month 12	-1.36 kU/L Interval -11.0 to -0.24	-0.92 kU/L Interval -7.33 to 0.58	-4.02 kU/L Interval -14.5 to -1.63	-2.29 kU/L Interval -7.0 to -0.01

SECONDARY outcome

Timeframe: From baseline to Week 3, Month 3, Month 6, Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Median change from baseline in levels of IgG4 specific to caseins, α-lactalbumin and β-lactoglobulin proteins

Outcome measures

Measure	Viaskin Milk 150 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Week 3	0.11 mgA/L Interval -0.06 to 0.25	0.15 mgA/L Interval -0.07 to 1.05	0.15 mgA/L Interval -0.14 to 1.19	0.03 mgA/L Interval -0.22 to 0.17
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Month 3	0.39 mgA/L Interval 0.0 to 0.99	1.08 mgA/L Interval 0.31 to 2.66	0.78 mgA/L Interval 0.11 to 2.0	-0.06 mgA/L Interval -0.35 to 0.14
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Month 6	0.32 mgA/L Interval 0.14 to 1.64	1.04 mgA/L Interval 0.2 to 2.69	0.69 mgA/L Interval 0.19 to 1.75	-0.01 mgA/L Interval -0.37 to 0.14
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin Caseins - Month 12	0.47 mgA/L Interval -0.18 to 1.47	1.05 mgA/L Interval 0.04 to 2.73	0.61 mgA/L Interval 0.1 to 4.43	-0.11 mgA/L Interval -0.51 to 0.17
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Week 3	0.00 mgA/L Interval -0.07 to 0.17	0.06 mgA/L Interval -0.01 to 0.43	0.00 mgA/L Interval -0.05 to 0.65	0.00 mgA/L Interval -0.08 to 0.09
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Month 3	0.63 mgA/L Interval 0.22 to 1.19	0.81 mgA/L Interval 0.23 to 2.04	0.65 mgA/L Interval 0.0 to 2.32	0.00 mgA/L Interval -0.05 to 0.13
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Month 6	1.09 mgA/L Interval 0.25 to 2.2	1.64 mgA/L Interval 0.62 to 2.8	1.19 mgA/L Interval 0.08 to 3.48	0.00 mgA/L Interval -0.04 to 0.13
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin α-lactalbumin - Month 12	1.28 mgA/L Interval 0.52 to 3.48	2.72 mgA/L Interval 0.74 to 7.38	1.94 mgA/L Interval 0.46 to 6.46	0.00 mgA/L Interval -0.18 to 0.08
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Week 3	0.03 mgA/L Interval -0.01 to 0.24	0.08 mgA/L Interval -0.03 to 0.29	0.11 mgA/L Interval -0.02 to 0.61	0.00 mgA/L Interval -0.1 to 0.07
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Month 3	0.22 mgA/L Interval 0.01 to 1.0	0.67 mgA/L Interval 0.35 to 1.73	0.65 mgA/L Interval 0.12 to 2.11	-0.01 mgA/L Interval -0.21 to 0.13
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Month 6	0.36 mgA/L Interval 0.04 to 1.2	0.94 mgA/L Interval 0.33 to 2.37	0.88 mgA/L Interval 0.06 to 2.3	-0.03 mgA/L Interval -0.2 to 0.11
Change in Levels of sIgG4 to Caseins, α-lactalbumin and β-lactoglobulin β-lactoglobulin - Month 12	0.47 mgA/L Interval 0.09 to 2.17	2.06 mgA/L Interval 0.63 to 4.78	1.55 mgA/L Interval 0.23 to 3.33	-0.06 mgA/L Interval -0.27 to 0.03

SECONDARY outcome

Timeframe: From baseline to Month 3, Month 6, Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Median change from baseline in SPT Wheal diameter

Outcome measures

Measure	Viaskin Milk 150 mcg n=48 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=46 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=52 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in Skin Prick Test (SPT) Wheal. Month 12	0 millimeters (mm) Interval -4.0 to 3.0	-1 millimeters (mm) Interval -4.0 to 1.0	-1 millimeters (mm) Interval -3.0 to 2.0	0 millimeters (mm) Interval -3.0 to 2.0
Change in Skin Prick Test (SPT) Wheal. Month 3	-1 millimeters (mm) Interval -3.0 to 2.0	-1 millimeters (mm) Interval -4.0 to 2.0	-1 millimeters (mm) Interval -3.0 to 2.0	0 millimeters (mm) Interval -3.0 to 4.0
Change in Skin Prick Test (SPT) Wheal. Month 6	0 millimeters (mm) Interval -3.0 to 3.0	-2 millimeters (mm) Interval -4.0 to 1.0	-1 millimeters (mm) Interval -4.0 to 1.0	0 millimeters (mm) Interval -4.0 to 3.0

SECONDARY outcome

Timeframe: From baseline to Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Summary of total objective severity score for DBPCFC. The total objective severity score is calculated as the sum of the severity grades (0-Absent, 1-Mild, 2-Moderate or 3-Severe) of the following objective symptoms: pruritus, urticaria/angioedema, rash, sneezing/itching, nasal congestion, rhinorrhea, laryngeal, wheezing, diarrhea, vomiting, cardiovascular and conjunctivitis for DBPCFC with cow's milk formula.

The total objective score ranges from a minimum of 0 to a maximum of 36 (if the maximum grade 3 was reported for each of the 12 symptoms), with a higher score meaning a worse outcome. A negative score in the changes to Month 0 means improvement.

Outcome measures

Measure	Viaskin Milk 150 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). Month 0	6 score on a scale Interval 4.0 to 9.0	6 score on a scale Interval 4.0 to 8.0	6 score on a scale Interval 4.0 to 10.0	6 score on a scale Interval 4.0 to 9.0
Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). Month 12	5 score on a scale Interval 4.0 to 9.0	6 score on a scale Interval 3.0 to 9.0	6 score on a scale Interval 4.0 to 9.0	6 score on a scale Interval 3.0 to 10.0
Change in the Severity of Symptoms Elicited During the Milk Double-Blind Placebo-Controlled Food Challenge (DBPCFC). Change from Month 0 to Month 12	-1 score on a scale Interval -3.0 to 3.0	0 score on a scale Interval -2.0 to 2.0	0 score on a scale Interval -2.0 to 2.0	0 score on a scale Interval -3.0 to 3.0

SECONDARY outcome

Timeframe: From baseline to Month 12 (double-blind period)

Population: All subjects from the Intent-to-Treat population for whom this outcome measure was collected and analyzed

Summary of Global Score for Food Allergy Quality of Life Questionnaire Parent Child Form (FAQLQ-PF). The scores range from 1 (no problem/impairment) to 7 (maximal problem/impairment). A negative score in the changes to Month 0 means improvement.

Outcome measures

Measure	Viaskin Milk 150 mcg n=39 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=39 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=41 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=44 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Change in Quality of Life (QoL) Assessments. Change from Month 0 to Month 12	-0.1 score on a scale Interval -0.6 to 0.5	0.1 score on a scale Interval -0.2 to 0.5	0 score on a scale Interval -0.8 to 0.5	-0.4 score on a scale Interval -0.8 to 0.5
Change in Quality of Life (QoL) Assessments. Month 0	4.6 score on a scale Interval 3.3 to 5.4	4.4 score on a scale Interval 3.4 to 5.2	4.6 score on a scale Interval 3.6 to 5.2	4.9 score on a scale Interval 3.3 to 5.5
Change in Quality of Life (QoL) Assessments. Month 12	4.3 score on a scale Interval 3.4 to 5.2	4.5 score on a scale Interval 3.5 to 5.4	4.3 score on a scale Interval 3.7 to 5.1	4.1 score on a scale Interval 3.4 to 5.2

SECONDARY outcome

Timeframe: From baseline to Month 12 and Month 24 after switch to Viaskin Milk 300µg (Open-Label 300µg period)

Population: All subjects from the Open-Label Set 300 (OLS-300) for whom this outcome measure was collected and analyzed. OLS-300 includes all subjects who entered the open-label treatment period after switch to Viaskin Milk 300µg and applied at least one Viaskin Milk 300µg patch during this open-label period.

A treatment responder is defined as a subject who meets at least one of the following criteria:

A ≥10-fold increase in the Cumulative Reactive Dose (CRD) of cow's milk proteins at the Month 12 double-blind placebo-controlled food challenge (DBPCFC) as compared to baseline value and reaching at least 144 mg of cow's milk proteins; A CRD of cow's milk proteins ≥1444 mg at the Month 12 DBPCFC.

DBPCFC at Month 12 and Month 24 after switch to Viaskin Milk 300µg was optional and therefore outcome measure was assessed on observed data only.

Outcome measures

Measure	Viaskin Milk 150 mcg n=15 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=13 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=8 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=14 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data Month 12 after switch to Viaskin Milk 300µg	85.7 Percentage of participants	72.7 Percentage of participants	62.5 Percentage of participants	81.8 Percentage of participants
Percentage (%) of Subjects Who Are Treatment Responders Over the Course of the Viaskin Milk 300µg Open-label Treatment Period Using Observed Data Month 24 after switch to Viaskin Milk 300µg	80.0 Percentage of participants	84.6 Percentage of participants	50.0 Percentage of participants	64.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24 after switch to Viaskin Milk 300µg (Open-Label 300µg period)

Population: All subjects from the Open-Label Set 300 (OLS-300) for whom this outcome measure was collected and analyzed. OLS-300 includes all subjects who entered the open-label treatment period after switch to Viaskin Milk 300µg and applied at least one Viaskin Milk 300µg patch during this open-label period.

Median CRD during Double-Blind Placebo-Controlled Food Challenge expressed in mg of cow's milk proteins.

Outcome measures

Measure	Viaskin Milk 150 mcg n=34 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=38 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=29 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=39 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period Month 0	144 milligrams (mg) of cow's milk proteins Interval 44.0 to 444.0	144 milligrams (mg) of cow's milk proteins Interval 44.0 to 444.0	144 milligrams (mg) of cow's milk proteins Interval 44.0 to 444.0	144 milligrams (mg) of cow's milk proteins Interval 44.0 to 444.0
Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period Month 24 after switch to Viaskin Milk 300µg	1444 milligrams (mg) of cow's milk proteins Interval 474.0 to 3444.0	1444 milligrams (mg) of cow's milk proteins Interval 444.0 to 3444.0	1219 milligrams (mg) of cow's milk proteins Interval 144.0 to 2819.0	1444 milligrams (mg) of cow's milk proteins Interval 444.0 to 6444.0
Cumulative Reactive Dose (CRD) of Cow's Milk Protein Over the Course of the Open-label Treatment Period Month 12 after switch to Viaskin Milk 300µg	1444 milligrams (mg) of cow's milk proteins Interval 944.0 to 6444.0	1444 milligrams (mg) of cow's milk proteins Interval 444.0 to 2194.0	1319 milligrams (mg) of cow's milk proteins Interval 444.0 to 3481.0	1444 milligrams (mg) of cow's milk proteins Interval 444.0 to 6444.0

SECONDARY outcome

Timeframe: Whole study including double-blind and open-label periods (up to 6 years).

Population: Safety set. It includes all subjects who applied at least one Viaskin patch.

Overview of Treatment Emergent Adverse Events (TEAEs) and serious Treatment-Emergent Adverse Events

Outcome measures

Measure	Viaskin Milk 150 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 150 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 150 mcg cow's milk proteins.	Viaskin Milk 300 mcg n=49 Participants One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 300 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 300 mcg cow's milk proteins.	Viaskin Milk 500 mcg n=47 Participants One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months. Viaskin Milk 500 mcg: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.	Viaskin Placebo n=53 Participants One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months. Viaskin Placebo: Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
Treatment-Emergent Adverse Events Any TEAE leading to death	0 participants	0 participants	0 participants	0 participants
Treatment-Emergent Adverse Events Any TEAE	49 participants	48 participants	47 participants	53 participants
Treatment-Emergent Adverse Events Any serious TEAE	9 participants	6 participants	6 participants	7 participants
Treatment-Emergent Adverse Events Any TEAE related to the Investigational Product	46 participants	43 participants	39 participants	48 participants
Treatment-Emergent Adverse Events Any serious TEAE related to the Investigational Product	0 participants	0 participants	0 participants	0 participants

Adverse Events

Double-Blind Viaskin Milk 150 mcg

Serious events: 3 serious events

Other events: 49 other events

Deaths: 0 deaths

Double-Blind Viaskin Milk 300 mcg

Serious events: 2 serious events

Other events: 48 other events

Deaths: 0 deaths

Double-Blind Viaskin Milk 500 mcg

Serious events: 1 serious events

Other events: 47 other events

Deaths: 0 deaths

Double-Blind Viaskin Placebo

Serious events: 2 serious events

Other events: 53 other events

Deaths: 0 deaths

Open-Label Viaskin Milk 500 mcg

Serious events: 16 serious events

Other events: 181 other events

Deaths: 0 deaths

Open-Label Viaskin Milk 300 mcg

Serious events: 7 serious events

Other events: 131 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-Blind Viaskin Milk 150 mcg n=49 participants at risk One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months (double-blind period).	Double-Blind Viaskin Milk 300 mcg n=49 participants at risk One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months (double-blind period).	Double-Blind Viaskin Milk 500 mcg n=47 participants at risk One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months (double-blind period).	Double-Blind Viaskin Placebo n=53 participants at risk One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months (double-blind period).	Open-Label Viaskin Milk 500 mcg n=185 participants at risk One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for up to 3 years. Open-Label Set 500 (OLS-500) that includes all subjects who entered the OL-500 period and applied at least one Viaskin Milk 500µg patch during this Open-Label period (N=185).	Open-Label Viaskin Milk 300 mcg n=140 participants at risk One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 24 months Open-Label Set 300 (OLS-300) that includes all subjects who entered the OL-300 period after switch to Viaskin Milk 300µg and applied at least one Viaskin Milk 300µg patch during this Open-label period (N=140).
Infections and infestations Appendicitis	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Pneumonia	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Cellulitis	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Croup Infectious	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Gastroenteritis viral	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Hand-foot-and-mouth disease	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Infective myositis	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Peritonitis	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Pneumonia influenzal	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Pyelonephritis	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Immune system disorders Anaphylactic reaction	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.7% 5/185 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 3/140 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Asthma	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Status Asthmaticus	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Nervous system disorders Encephalitis autoimmune	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Nervous system disorders Epilepsy	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Nervous system disorders Loss of consciousness	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Injury, poisoning and procedural complications Road Traffic accident	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.1% 2/185 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Injury, poisoning and procedural complications Concussion	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Injury, poisoning and procedural complications craniocerebral injury	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Injury, poisoning and procedural complications Laceration	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Injury, poisoning and procedural complications Traumatic liver injury	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Eye disorders Retinal detachment	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Eosinophilic oesophagitis	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Psychiatric disorders Suicide attempt	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.

Other adverse events

Measure	Double-Blind Viaskin Milk 150 mcg n=49 participants at risk One Viaskin epicutaneous delivery system (patch) containing 150µg of cow's milk proteins applied each day for 12 months (double-blind period).	Double-Blind Viaskin Milk 300 mcg n=49 participants at risk One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 12 months (double-blind period).	Double-Blind Viaskin Milk 500 mcg n=47 participants at risk One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for 12 months (double-blind period).	Double-Blind Viaskin Placebo n=53 participants at risk One Viaskin epicutaneous delivery system (patch) containing placebo applied each day for 12 months (double-blind period).	Open-Label Viaskin Milk 500 mcg n=185 participants at risk One Viaskin epicutaneous delivery system (patch) containing 500µg of cow's milk proteins applied each day for up to 3 years. Open-Label Set 500 (OLS-500) that includes all subjects who entered the OL-500 period and applied at least one Viaskin Milk 500µg patch during this Open-Label period (N=185).	Open-Label Viaskin Milk 300 mcg n=140 participants at risk One Viaskin epicutaneous delivery system (patch) containing 300µg of cow's milk proteins applied each day for 24 months Open-Label Set 300 (OLS-300) that includes all subjects who entered the OL-300 period after switch to Viaskin Milk 300µg and applied at least one Viaskin Milk 300µg patch during this Open-label period (N=140).
General disorders Application site papules	10.2% 5/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.2% 4/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.6% 14/185 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.3% 13/140 • Number of events 15 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Upper respiratory tract infection	55.1% 27/49 • Number of events 57 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	46.9% 23/49 • Number of events 45 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	34.0% 16/47 • Number of events 32 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	35.8% 19/53 • Number of events 33 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	32.4% 60/185 • Number of events 125 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	27.1% 38/140 • Number of events 73 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Viral upper respiratory tract infection	22.4% 11/49 • Number of events 24 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.4% 9/49 • Number of events 20 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	23.4% 11/47 • Number of events 21 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.9% 10/53 • Number of events 21 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.4% 34/185 • Number of events 56 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	15.7% 22/140 • Number of events 45 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Influenza	8.2% 4/49 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	11.3% 6/53 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	15.7% 29/185 • Number of events 29 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	16.4% 23/140 • Number of events 30 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Gastroenteritis viral	14.3% 7/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	11.4% 21/185 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.1% 10/140 • Number of events 12 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Viral infection	6.1% 3/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.2% 4/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.1% 15/185 • Number of events 16 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	14.3% 20/140 • Number of events 35 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Pharyngitis streptococcal	8.2% 4/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	12.8% 6/47 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	13.2% 7/53 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.1% 15/185 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 6/140 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Gastroenteritis	8.2% 4/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.1% 15/185 • Number of events 21 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 9/140 • Number of events 11 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Otitis media	10.2% 5/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.1% 2/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 3/53 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.4% 10/185 • Number of events 13 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Ear infection	12.2% 6/49 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 8/185 • Number of events 12 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Pneumonia	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.4% 10/185 • Number of events 13 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.9% 4/140 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Sinusitis	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.2% 4/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 2/47 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 3/53 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.4% 10/185 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 3/140 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Impetigo	2.0% 1/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.8% 2/53 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.2% 4/185 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.4% 2/140 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Conjunctivitis	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 3/53 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.6% 3/185 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Infections and infestations Croup infectious	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.54% 1/185 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site erythema	59.2% 29/49 • Number of events 129 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	51.0% 25/49 • Number of events 182 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	51.1% 24/47 • Number of events 64 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	30.2% 16/53 • Number of events 45 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	49.7% 92/185 • Number of events 386 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	27.9% 39/140 • Number of events 240 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site pruritus	53.1% 26/49 • Number of events 106 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	53.1% 26/49 • Number of events 128 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	38.3% 18/47 • Number of events 71 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.9% 10/53 • Number of events 26 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	46.5% 86/185 • Number of events 395 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	21.4% 30/140 • Number of events 158 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site swelling	28.6% 14/49 • Number of events 78 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	26.5% 13/49 • Number of events 51 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	29.8% 14/47 • Number of events 40 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 3/53 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	25.4% 47/185 • Number of events 222 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.0% 14/140 • Number of events 103 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Pyrexia	22.4% 11/49 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	14.3% 7/49 • Number of events 12 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 12 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	22.6% 12/53 • Number of events 18 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	15.7% 29/185 • Number of events 41 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	15.0% 21/140 • Number of events 23 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site urticaria	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.4% 9/49 • Number of events 16 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 2/47 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.6% 16/185 • Number of events 34 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site eczema	14.3% 7/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	12.2% 6/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.4% 5/53 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.6% 14/185 • Number of events 15 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site erosion	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.1% 2/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.2% 6/185 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.9% 11/140 • Number of events 12 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site rash	8.2% 4/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.2% 4/185 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.4% 2/140 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Chest Discomfort	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.1% 2/185 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site vesicles	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.1% 2/185 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Asthma	38.8% 19/49 • Number of events 32 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	20.4% 10/49 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	29.8% 14/47 • Number of events 46 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	37.7% 20/53 • Number of events 52 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	26.5% 49/185 • Number of events 114 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	26.4% 37/140 • Number of events 101 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Cough	26.5% 13/49 • Number of events 24 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	20.4% 10/49 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	14.9% 7/47 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	24.5% 13/53 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.3% 19/185 • Number of events 28 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.9% 11/140 • Number of events 21 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	8.2% 4/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	12.2% 6/49 • Number of events 13 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.8% 2/53 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.1% 15/185 • Number of events 25 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	13.6% 19/140 • Number of events 32 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Nasal congestion	20.4% 10/49 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	16.3% 8/49 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.9% 11/185 • Number of events 17 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 8/140 • Number of events 22 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Wheezing	12.2% 6/49 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	13.2% 7/53 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.2% 17/185 • Number of events 34 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 3/140 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 2/47 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.9% 10/53 • Number of events 16 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.2% 6/185 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.2% 4/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 2/47 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 3/53 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.9% 9/185 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Throat irritation	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.9% 9/185 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Respiratory, thoracic and mediastinal disorders Sneezing	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.2% 5/49 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.8% 2/53 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.7% 5/185 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Immune system disorders Anaphylactic reaction	36.7% 18/49 • Number of events 26 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	20.4% 10/49 • Number of events 11 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	31.9% 15/47 • Number of events 19 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	20.8% 11/53 • Number of events 18 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	24.3% 45/185 • Number of events 67 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	18.6% 26/140 • Number of events 31 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Immune system disorders Hypersensitivity	20.4% 10/49 • Number of events 15 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	21.3% 10/47 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	17.0% 9/53 • Number of events 16 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	17.8% 33/185 • Number of events 43 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	17.9% 25/140 • Number of events 40 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Immune system disorders Food Allergy	14.3% 7/49 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	12.2% 6/49 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	11.3% 6/53 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	11.9% 22/185 • Number of events 36 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	15.0% 21/140 • Number of events 30 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Immune system disorders Seasonal allergy	12.2% 6/49 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.2% 4/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.2% 17/185 • Number of events 24 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 11 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Immune system disorders Allergy to animal	4.1% 2/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.2% 4/49 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.2% 6/185 • Number of events 11 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 9/140 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Skin and subcutaneous tissue disorders Urticaria	26.5% 13/49 • Number of events 24 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	28.6% 14/49 • Number of events 18 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	23.4% 11/47 • Number of events 25 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	13.2% 7/53 • Number of events 29 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	11.4% 21/185 • Number of events 30 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	12.1% 17/140 • Number of events 27 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Skin and subcutaneous tissue disorders Eczema	22.4% 11/49 • Number of events 23 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.2% 5/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	19.1% 9/47 • Number of events 21 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	13.2% 7/53 • Number of events 16 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	13.0% 24/185 • Number of events 35 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.1% 10/140 • Number of events 12 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Skin and subcutaneous tissue disorders Rash	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.5% 12/185 • Number of events 20 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.0% 7/140 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Skin and subcutaneous tissue disorders Pruritus	8.2% 4/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 2/47 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.9% 1/53 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.8% 7/185 • Number of events 11 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.9% 4/140 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Skin and subcutaneous tissue disorders Erythema	6.1% 3/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 3/53 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.7% 5/185 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 3/140 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Vomiting	14.3% 7/49 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.2% 5/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.7% 18/185 • Number of events 21 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.0% 7/140 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Diarrhoea	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	14.3% 7/49 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.4% 5/53 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.2% 4/185 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.7% 8/140 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Oral pruritus	6.1% 3/49 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	8.5% 4/47 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 8/185 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Abdominal pain upper	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.5% 4/53 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.3% 8/185 • Number of events 9 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Abdominal pain	10.2% 5/49 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.4% 3/47 • Number of events 4 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.8% 2/53 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.2% 4/185 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.6% 5/140 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Nausea	2.0% 1/49 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	3.2% 6/185 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 3/140 • Number of events 5 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Gastrointestinal disorders Toothache	8.2% 4/49 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	1.6% 3/185 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Nervous system disorders Headache	10.2% 5/49 • Number of events 14 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.2% 5/49 • Number of events 8 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	10.6% 5/47 • Number of events 23 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	9.4% 5/53 • Number of events 6 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	6.5% 12/185 • Number of events 25 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	7.1% 10/140 • Number of events 27 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Eye disorders Eye swelling	6.1% 3/49 • Number of events 10 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	4.1% 2/49 • Number of events 2 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.7% 5/185 • Number of events 7 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Musculoskeletal and connective tissue disorders Neck pain	6.1% 3/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/47 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/185 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
Reproductive system and breast disorders Dysmenorrhoea	10.2% 5/49 • Number of events 26 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.7% 5/185 • Number of events 19 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/140 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.
General disorders Application site oedema	2.0% 1/49 • Number of events 3 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/49 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	2.1% 1/47 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.00% 0/53 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	5.4% 10/185 • Number of events 13 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.	0.71% 1/140 • Number of events 1 • Adverse events collected over the entire course of the study including the double-blind period and the open-label periods, up to 6 years overall. Treatment-Emergent Adverse events during the whole study period.

Additional Information

Pharis Mohideen, MD Chief Medical Officer

DBV Technologies

Phone: 908-679-5200

Email: clinicaltrials@dbv-technologies.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place