Trial Outcomes & Findings for Efficacy and Safety Study of RAGWITEK™ (MK-3641) in Children With Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (MK-3641-008) (NCT NCT02478398)

Last Updated: 2019-09-06

Results Overview

TCS is daily symptom score (DSS) plus daily medication score (DMS), assessed in the peak RS (15 consecutive RS days with the highest 15-day average pollen count). The rhinoconjunctivitis (RC) DSS assesses 6 allergy symptoms measured on a scale of 0 to 3 (0=no symptoms, 3=severe symptoms; score range: 0-18). Lower DSS indicates less RC symptoms. The RC DMS is based on use of RC rescue medications (loratadine, olopatadine, mometasone), with different rescue medications being assigned different scores/dose unit (score range: 0-20). Lower DMS indicates less RC medication use. Summed RC DSS+DMS could range from 0 to 38; a lower score indicates less RC symptoms and medication use. Components that contribute to DSS and DMS endpoints are collected in an electronic diary (e-diary) completed by the participant/parent/guardian. Evaluation is based on average TCS during peak RS.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1025 participants

Primary outcome timeframe

The 15-day period during the ragweed season with the highest moving pollen average

Results posted on

2019-09-06

Participant Flow

Participant milestones

Participant milestones
Measure	Short Ragweed Pollen Allergen Extract Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, once daily (QD) for up to 35 weeks.	Placebo Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Overall Study STARTED	513	512
Overall Study Treated	512	510
Overall Study COMPLETED	461	491
Overall Study NOT COMPLETED	52	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Short Ragweed Pollen Allergen Extract Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, once daily (QD) for up to 35 weeks.	Placebo Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Overall Study Adverse Event	20	5
Overall Study Lost to Follow-up	5	4
Overall Study Non-Compliance With Study Drug	5	1
Overall Study Protocol Violation	3	1
Overall Study Withdrawal By Parent/Guardian	9	6
Overall Study Withdrawal By Participant	10	4

Baseline Characteristics

Efficacy and Safety Study of RAGWITEK™ (MK-3641) in Children With Ragweed-Induced Rhinoconjunctivitis With or Without Asthma (MK-3641-008)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Short Ragweed Pollen Allergen Extract n=512 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=510 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.	Total n=1022 Participants Total of all reporting groups
Age, Continuous	12.1 years STANDARD_DEVIATION 3.2 • n=5 Participants	12.2 years STANDARD_DEVIATION 3.1 • n=7 Participants	12.1 years STANDARD_DEVIATION 3.1 • n=5 Participants
Age, Customized < 12 years	206 Participants n=5 Participants	204 Participants n=7 Participants	410 Participants n=5 Participants
Age, Customized ≥ 12 years	306 Participants n=5 Participants	306 Participants n=7 Participants	612 Participants n=5 Participants
Sex: Female, Male Female	188 Participants n=5 Participants	191 Participants n=7 Participants	379 Participants n=5 Participants
Sex: Female, Male Male	324 Participants n=5 Participants	319 Participants n=7 Participants	643 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) White	473 Participants n=5 Participants	477 Participants n=7 Participants	950 Participants n=5 Participants
Race (NIH/OMB) More than one race	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	15 Participants n=5 Participants	21 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	490 Participants n=5 Participants	483 Participants n=7 Participants	973 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Baseline Asthma Status Yes	219 Participants n=5 Participants	217 Participants n=7 Participants	436 Participants n=5 Participants
Baseline Asthma Status No	293 Participants n=5 Participants	293 Participants n=7 Participants	586 Participants n=5 Participants

PRIMARY outcome

Timeframe: The 15-day period during the ragweed season with the highest moving pollen average

Population: The analysis population includes all treated participants w/ ≥1 e-diary entry for the specified measurement and timeframe.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=460 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=487 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Total Combined Score (TCS) During the Peak Ragweed Season (RS)	4.39 Score on a scale 95% Confidence Interval 3.85 • Interval 3.85 to 4.94	7.12 Score on a scale 95% Confidence Interval 6.57 • Interval 6.57 to 7.67

SECONDARY outcome

Timeframe: Up to 13 weeks

Population: The analysis population includes all treated participants w/ ≥1 e-diary entry for the specified measurement and timeframe.

TCS is DSS plus DMS, assessed here during the entire RS. This starts from the first day of 3 consecutive days with ragweed pollen counts ≥10 grains/m\^3 through the last day of the last occurrence of 3 consecutive days with ragweed pollen counts ≥10 grains/m\^3. The duration of the entire RS is up to 13 weeks; this duration varies by site/region. The RC DSS assesses 6 allergy symptoms measured on a scale of 0 to 3 (score range: 0-18). A lower DSS indicates less RC symptoms. The RC DMS is based on use of RC rescue medications (loratadine, olopatadine, mometasone) with different scores/dose unit (score range: 0-20). A lower DMS indicates less RC medication use. The sum of RC DSS+DMS ranges from 0 to 38, with a lower score indicating less RC symptoms and medication use. Components contributing to the TCS for the entire RS are collected in an e-diary completed by the participant/parent/guardian.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=466 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=491 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Average TCS During the Entire RS	3.88 Score on a scale 95% Confidence Interval 3.44 • Interval 3.44 to 4.33	5.75 Score on a scale 95% Confidence Interval 5.30 • Interval 5.3 to 6.2

SECONDARY outcome

Timeframe: The 15-day period during the ragweed season with the highest moving pollen average

Population: The analysis population includes all treated participants w/ ≥1 e-diary entry for the specified measurement and timeframe.

The DSS consists of a total of 6 rhinoconjunctivitis symptoms: 4 rhinitis symptoms (runny nose, stuffy nose, sneezing, itchy nose) and 2 conjunctivitis symptoms (itchy eyes, watery eyes). The components that contribute to the DSS endpoint are collected in an e-diary completed by the participant/parent/guardian. The RC DSS is measured on a 4-point scale from 0 to 3 as follows: 0 (no sign/symptom evident) to 3 (sign/symptom that is hard to tolerate; may cause interference with activities of daily living and/or sleeping). The maximum DSS is 18 points if a participant experiences all 6 symptoms with an intensity of 3 for each symptom. The minimum DSS is 0 points if a participant experiences no symptoms. A lower DSS means symptoms are less severe. The evaluation is based on the average DSS during the peak RS.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=468 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=494 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Average Rhinoconjunctivitis (RC) DSS During the Peak RS	2.55 Score on a scale 95% Confidence Interval 2.24 • Interval 2.24 to 2.86	3.95 Score on a scale 95% Confidence Interval 3.63 • Interval 3.63 to 4.26

SECONDARY outcome

Timeframe: The 15-day period during the ragweed season with the highest moving pollen average

Population: The analysis population includes all treated participants w/ ≥1 e-diary entry for the specified measurement and timeframe.

This DMS endpoint consists of a total of scores for use of RC medications: loratadine syrup or tablets (6 points), olopatadine (6 points), and mometasone (8 points). The score range of the RC DMS is 0-20 points, and a lower DMS means that less medication is used. The method used for analysis of the RC DMS is a zero-inflated log-normal model, which takes the average RC DMS during the peak RS as the response and adjusts for the same terms as in the ANOVA model. The components that contribute to the DMS endpoint are collected in an e-diary completed by the participant/parent/guardian.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=460 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=487 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Average Rhinoconjunctivitis (RC) DMS During the Peak RS	2.01 Score on a scale 95% Confidence Interval 1.57 • Interval 1.57 to 2.46	3.85 Score on a scale 95% Confidence Interval 3.14 • Interval 3.14 to 4.57

SECONDARY outcome

Timeframe: Up to 35 weeks

Population: The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.

Pre-specified local application site reactions, irrespective of causality, included AEs related to lip swelling/edema, mouth swelling/edema, palatal swelling/edema, swollen tongue/edema, oropharyngeal swelling/edema, pharyngeal edema/throat tightness, oral pruritus, throat irritation, tongue pruritus, and ear pruritus.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=513 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=509 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Percentage of Participants Reporting Pre-specified Local Application Site Reactions	64.52 Percentage of Participants	26.92 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 35 weeks

For the purposes of this study, systemic allergic reactions are allergic reactions that occur away from the site of study drug application (allergic reactions other than local application site reactions). Anaphylaxis is a severe allergic reaction that typically involves more than one body system.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=513 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=509 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Percentage of Participants Reporting Anaphylaxis and/or Systemic Allergic Reactions	0.58 Percentage of Participants	0.20 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 35 weeks

Self-injectable epinephrine was provided to each participant/parent/guardian at randomization in countries where it is a regulatory requirement, and was to be available around the time treatment is administered at home. Self-injectable epinephrine was intended for immediate self-administration for an anaphylactic reaction, including symptoms/signs of upper airway obstruction. Instances of treatment with forms of epinephrine other than systemic epinephrine (e.g., inhaled racepinephrine) were counted as use of epinephrine.

Outcome measures

Outcome measures
Measure	Short Ragweed Pollen Allergen Extract n=513 Participants Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=509 Participants Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Percentage of Participants Treated With Epinephrine	0.19 Percentage of Participants	0.20 Percentage of Participants

Adverse Events

Short Ragweed Pollen Allergen Extract

Serious events: 7 serious events

Other events: 370 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 233 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Short Ragweed Pollen Allergen Extract n=513 participants at risk Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=509 participants at risk Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Gastrointestinal disorders Abdominal pain	0.00% 0/513 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.20% 1/509 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Oral pruritus	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.00% 0/509 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Immune system disorders Hypersensitivity	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.20% 1/509 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Infections and infestations Campylobacter gastroenteritis	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.00% 0/509 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Infections and infestations Laryngitis	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.00% 0/509 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Infections and infestations Viral infection	0.00% 0/513 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.20% 1/509 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Injury, poisoning and procedural complications Concussion	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.00% 0/509 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Psychiatric disorders Conduct disorder	0.00% 0/513 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.20% 1/509 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/513 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.59% 3/509 • Number of events 3 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Infections and infestations Gastroenteritis viral	0.00% 0/513 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.20% 1/509 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/513 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.20% 1/509 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Injury, poisoning and procedural complications Upper limb fracture	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.00% 0/509 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Infections and infestations Gastrointestinal viral inection	0.19% 1/513 • Number of events 1 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.00% 0/509 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Short Ragweed Pollen Allergen Extract n=513 participants at risk Participants received one short ragweed pollen allergen extract sublingual tablet containing 12 units of Amb a 1-U, QD for up to 35 weeks.	Placebo n=509 participants at risk Participants received one placebo sublingual tablet, QD for up to 35 weeks.
Ear and labyrinth disorders Ear pruritus	34.5% 177/513 • Number of events 750 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	6.9% 35/509 • Number of events 65 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Abdominal pain upper	10.5% 54/513 • Number of events 119 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	5.9% 30/509 • Number of events 53 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Diarrhoea	5.1% 26/513 • Number of events 55 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	4.1% 21/509 • Number of events 29 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Enlarged uvula	6.4% 33/513 • Number of events 65 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.39% 2/509 • Number of events 2 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Glossodynia	12.5% 64/513 • Number of events 171 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	2.6% 13/509 • Number of events 29 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Lip swelling	12.9% 66/513 • Number of events 165 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	1.4% 7/509 • Number of events 14 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Nausea	13.6% 70/513 • Number of events 167 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	8.4% 43/509 • Number of events 69 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Oral pain	12.5% 64/513 • Number of events 151 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	3.1% 16/509 • Number of events 29 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Oral pruritus	48.1% 247/513 • Number of events 1115 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	12.2% 62/509 • Number of events 131 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Stomatitis	6.6% 34/513 • Number of events 89 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	1.2% 6/509 • Number of events 13 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Gastrointestinal disorders Swollen tongue	10.9% 56/513 • Number of events 132 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	0.79% 4/509 • Number of events 5 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
General disorders Pyrexia	5.7% 29/513 • Number of events 33 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	3.9% 20/509 • Number of events 23 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Infections and infestations Nasopharyngitis	7.4% 38/513 • Number of events 50 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	7.1% 36/509 • Number of events 50 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Nervous system disorders Headache	8.8% 45/513 • Number of events 100 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	9.6% 49/509 • Number of events 67 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Respiratory, thoracic and mediastinal disorders Cough	5.8% 30/513 • Number of events 39 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	5.9% 30/509 • Number of events 53 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.9% 25/513 • Number of events 56 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	5.7% 29/509 • Number of events 44 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	11.3% 58/513 • Number of events 138 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	1.6% 8/509 • Number of events 14 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.
Respiratory, thoracic and mediastinal disorders Throat irritation	49.5% 254/513 • Number of events 1048 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.	19.3% 98/509 • Number of events 223 • Up to 35 weeks An AE is any physical or clinical change or disease experienced by the participant at any time during the course of the study, whether or not considered related to the use of the study drug. The safety population was all participants as treated. One participant was randomized to placebo but received short ragweed pollen allergen extract for one day and is included in the short ragweed pollen allergen extract arm.