Efficacy of the Anti-Bet v 1 Monoclonal Antibodies (Given Subcutaneously) to Reduce Allergic Rhinitis and Conjunctivitis Symptoms and Skin Test Reactivity Upon Exposure to Birch Allergen in Adult Participants

Study Overview
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Brief Summary
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Primary objective: To assess the efficacy of a single dose of the anti- Bet v 1 monoclonal antibodies (mAb(s ) in the reduction of allergic nasal symptoms during an out-of-season birch allergen environmental exposure unit (EEU) challenge in participants receiving REGN5713-5714-5715 versus placebo (Part A)

Detailed Description
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The study consists of Part A and Part B. All participants will be asked to complete both Part A and Part B of the study. The study lasts for a total duration of up to approximately 46 weeks (including up to a 10-week screening period). Part A of the study lasts up to approximately 28 weeks (including the screening period). Part B of the study starts after completion of Part A and lasts up to approximately 18 weeks (including an approximately 4-week follow-up period after end of birch pollen season (BPS)), dependent on the start and end times of the natural BPS.

Official Title
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A Two-Part Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of the Anti-Bet v 1 Monoclonal Antibodies to Reduce Allergic Rhinitis and Conjunctivitis Symptoms and Skin Test Reactivity Upon Exposure to Birch Allergen

Conditions
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Allergic Rhinitis, Conjunctivitis

Intervention / Treatment
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* Drug: REGN5713
* Drug: REGN5714
* Drug: REGN5715
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented or participant-reported history of birch tree pollen-triggered allergic-rhinitis (AR) symptoms with or without conjunctivitis (for at least 2 seasons) Positive Skin prick test (SPT) with birch tree pollen extract (mean wheal diameter at least 5 mm greater than a negative control) in screening period Positive allergen-specific immunoglobulin E (sIgE) tests for birch tree pollen and Bet v 1 (≥0.7 kUa/L) in screening period Demonstrated TNSS ≥ 6 out of 12 on at least 2 time points during the birch EEU exposure challenge in screening period Key Exclusion Criteria: Participation in a prior REGN5713-5714-5715 clinical trial and received REGN5713-5714-5715 antibodies (receipt of placebo in a previous trial is allowed) Significant rhinitis, sinusitis, significant and/or severe allergies not associated with the birch pollen season, or due to daily contact with other non-birch related allergens causing symptoms that are expected to coincide or potentially interfere with the study EEU assessments or with the birch pollen season, as assessed by the investigator Participants who anticipate major changes in allergen exposure during the birch pollen season that are expected to coincide with study assessments or planned travel that is expected to interfere with the study assessments, as assessed by the investigator (eg. anticipated travel during planned EEU sessions or birch pollen season) Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections within 4 weeks prior to screening visit 1. Patients may be re-evaluated for eligibility after resolution of symptoms and specified duration. History of significant, recurrent sinusitis, defined as at least 3 episodes requiring antibiotic treatment per year for the last 2 years Abnormal lung function as judged by the investigator with Forced Expiratory Volume (FEV1) <75% of predicted at screening or randomization A clinical history of moderate to severe asthma, uncontrolled asthma, global initiative for asthma [GINA] steps 3 to 5, history of life-threatening asthma, asthma exacerbations due to tree pollen allergy within 2 prior seasons, >2 asthma exacerbations requiring systemic steroids in past 12 months, asthma related emergency care or hospitalization within 12 months prior to screening, as defined in the protocol. History of birch or other tree allergen immunotherapy in the 3 years prior to screening. Use of anti-IgE or other biological therapy (including but not limited to anti IL-5, anti IL-4) that interferes with type 2 disease within 6 months prior to screening visit 1. Allergen-specific immunotherapy with any allergen other than birch or other trees at screening. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease, Any malignancy within the past 5 years, except for basal cell or squamous epithelial cell carcinomas of the skin or carcinoma in situ of the cervix or anus that have been resected, with no evidence of local recurrence or metastatic disease for 3 years. NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN5713-5714-5715<br>3-mAb | Drug: REGN5713<br>* Administered subcutaneously (SC)<br>Drug: REGN5714<br>* Administered SC<br>Drug: REGN5715<br>* Administered SC<br>|
| Experimental: REGN5713-5715<br>2-mAb | Drug: REGN5713<br>* Administered subcutaneously (SC)<br>Drug: REGN5715<br>* Administered SC<br>Other: Placebo<br>* Administered SC<br>|
| Experimental: REGN5715<br>1-mAb | Drug: REGN5715<br>* Administered SC<br>Other: Placebo<br>* Administered SC<br>|
| Placebo Comparator: Matching Placebo<br> | Other: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of Total Nasal Symptom Score [TNSS (2 to 6 hours)] during a birch allergen environmental exposure unit (EEU) challenge | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of TNSS (2 to 6 hours) during out-of-season birch allergen EEU challenges except for 3-mAb vs Placebo at Day 29 | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Days 29, 57 and 85 | 
| Mean of TNSS (2 to 6 hours) during out-of-season birch allergen EEU challenges for 3-mAb only | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Days 57 and 85 | 
| Mean of Total Ocular Symptom Score (TOSS) (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Days 29, 57 and 85 | 
| Mean of Total Symptom Score (TSS) (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Days 29, 57 and 85 | 
| Change from pre-treatment baseline in TNSS (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Days 29, 57 and 85 | 
| Change from pre-treatment baseline in TOSS (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Days 29, 57 and 85 | 
| Change from pre-treatment baseline in TSS (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Days 29, 57 and 85 | 
| Percent change from pre-treatment baseline in TNSS (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Days 29, 57 and 85 | 
| Percent change from pre-treatment baseline in TOSS (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Days 29, 57 and 85 | 
| Percent change from pre-treatment baseline in TSS (2 to 6 hours) during out-of-season birch allergen EEU challenges | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Days 29, 57 and 85 | 
| Change from pre-treatment baseline in the birch (and related allergens) titrated Skin Prick Test (SPT) mean wheal diameter Area under the Curve (AUC) | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Days 29, 57, 85 and 127 | 
| Percent change from pre-treatment baseline in the birch (and related allergens) titrated SPT mean wheal diameter AUC | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Days 29, 57, 85 and 127 | 
| Mean of TNSS (2 to 6 hours) during out-of-season oak allergen EEU challenge | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Day 36 | 
| Mean of TOSS (2 to 6 hours) during out-of-season oak allergen EEU challenge | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Day 36 | 
| Mean of TSS (2 to 6 hours) during out-of-season oak allergen EEU challenge | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Day 36 | 
| Change from pre-treatment baseline in TNSS (2 to 6 hours) during an oak allergen EEU in subpopulation of oak-allergic participants | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Day 36 | 
| Change from pre-treatment baseline in TOSS (2 to 6 hours) during an oak allergen EEU in subpopulation of oak-allergic participants | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Day 36 | 
| Change from pre-treatment baseline in TSS (2 to 6 hours) during an oak allergen EEU in subpopulation of oak-allergic participants | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Day 36 | 
| Percent change from pre-treatment baseline in TNSS (2 to 6 hours) during an oak allergen EEU in subpopulation of oak-allergic participants | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Day 36 | 
| Percent change from pre-treatment baseline in TOSS (2 to 6 hours) during an oak allergen EEU in subpopulation of oak-allergic participants | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Day 36 | 
| Percent change from pre-treatment baseline in TSS (2 to 6 hours) during an oak allergen EEU in subpopulation of oak-allergic participants | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Day 36 | 
| Proportion of participants achieving different degrees of clinical responses will be compared across TNSS (2 to 6 hours) response threshold | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Days 29, 57 and 85 | 
| Proportion of participants achieving different degrees of clinical responses will be compared across TOSS (2 to 6 hours) response threshold | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Days 29, 57 and 85 | 
| Proportion of participants achieving different degrees of clinical responses will be compared across TSS (2 to 6 hours) response threshold | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Days 29, 57 and 85 | 
| Proportion of participants achieving different degrees of responses in the birch (and related allergens) titrated SPT mean wheal diameter AUC will be compared across different response thresholds | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Days 29, 57 and 85 | 
| Mean of TNSS (2 to 6 hours) during the peak-season birch allergen EEU challenge | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Mean of TOSS (2 to 6 hours) during the peak-season birch allergen EEU challenge | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| Mean of TSS (2 to 6 hours) during the peak-season birch allergen EEU challenge | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Daily Combined Symptom and Medication Score (CSMS) averaged during the BPS | The CSMS is defined as Total Symptom Score (TSS) plus Daily Medication Score (DMS). | Up to 253 Days | 
| Daily TSS averaged during the BPS | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Daily TNSS averaged during the BPS | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Daily TOSS averaged during the BPS | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| Daily Medication Score (DMS) averaged during the BPS | For the DMS, oral antihistamine 6 points/dose; maximum daily score 6 points, ocular antihistamine 1.5 points/drop; maximum daily score 6 points, intranasal corticosteroid 2.0 points/spray; maximum daily score 8 points). The maximum DMS score is 20. | Up to 253 Days | 
| Daily CSMS averaged during the peak BPS | The CSMS is defined as Total Symptom Score (TSS) plus Daily Medication Score (DMS). | Up to 253 Days | 
| Daily TSS averaged during the peak BPS | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Daily TNSS averaged during the peak BPS | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Daily TOSS averaged during the peak BPS | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| DMS averaged during the peak BPS | For the DMS, oral antihistamine 6 points/dose; maximum daily score 6 points, ocular antihistamine 1.5 points/drop; maximum daily score 6 points, intranasal corticosteroid 2.0 points/spray; maximum daily score 8 points). The maximum DMS score is 20. | Up to 253 Days | 
| Change from baseline in CSMS averaged during the BPS | The CSMS is defined as Total Symptom Score (TSS) plus Daily Medication Score (DMS). | Up to 253 Days | 
| Change from baseline in TSS averaged during the BPS | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Change from baseline in TNSS averaged during the BPS | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Change from baseline in TOSS averaged during the BPS | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| Change from baseline in DMS averaged during the BPS | For the DMS, oral antihistamine 6 points/dose; maximum daily score 6 points, ocular antihistamine 1.5 points/drop; maximum daily score 6 points, intranasal corticosteroid 2.0 points/spray; maximum daily score 8 points). The maximum DMS score is 20. | Up to 253 Days | 
| Change from baseline in CSMS averaged during the peak BPS | The CSMS is defined as Total Symptom Score (TSS) plus Daily Medication Score (DMS). | Up to 253 Days | 
| Change from baseline in TSS averaged during the peak BPS | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Change from baseline in TNSS averaged during the peak BPS | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Change from baseline in TOSS averaged during the peak BPS | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| Change from baseline in DMS averaged during the peak BPS | For the DMS, oral antihistamine 6 points/dose; maximum daily score 6 points, ocular antihistamine 1.5 points/drop; maximum daily score 6 points, intranasal corticosteroid 2.0 points/spray; maximum daily score 8 points). The maximum DMS score is 20. | Up to 253 Days | 
| Percentage change from baseline in CSMS averaged during the BPS | The CSMS is defined as Total Symptom Score (TSS) plus Daily Medication Score (DMS). | Up to 253 Days | 
| Percentage change from baseline in TSS averaged during the BPS | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Percentage change from baseline in TNSS averaged during the BPS | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Percentage change from baseline in TOSS averaged during the BPS | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| Percentage change from baseline in DMS averaged during the BPS | For the DMS, oral antihistamine 6 points/dose; maximum daily score 6 points, ocular antihistamine 1.5 points/drop; maximum daily score 6 points, intranasal corticosteroid 2.0 points/spray; maximum daily score 8 points). The maximum DMS score is 20. | Up to 253 Days | 
| Percentage change from baseline in CSMS averaged during the peak BPS | The CSMS is defined as Total Symptom Score (TSS) plus Daily Medication Score (DMS). | Up to 253 Days | 
| Percentage change from baseline in TSS averaged during the peak BPS | The TSS is calculated by adding the TNSS and TOSS together, for a combined TSS of 0 to 18. | Up to 253 Days | 
| Percentage change from baseline in TNSS averaged during the peak BPS | The TNSS ranges from 0 to 12 and is based on assessment of 4 nasal symptoms graded on a Likert scale ranging from 0 (none) to 3 (severe) for nasal congestion, itching, and runny nose, and sneezing. | Up to 253 Days | 
| Percentage change from baseline in TOSS averaged during the peak BPS | The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe). | Up to 253 Days | 
| Percentage change from baseline in DMS averaged during the peak BPS | For the DMS, oral antihistamine 6 points/dose; maximum daily score 6 points, ocular antihistamine 1.5 points/drop; maximum daily score 6 points, intranasal corticosteroid 2.0 points/spray; maximum daily score 8 points). The maximum DMS score is 20. | Up to 253 Days | 
| Change from pre-treatment baseline to end-of-season visits in the birch (and related allergens) titrated SPT mean wheal diameter AUC | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Up to 253 Days | 
| Change from pre-treatment baseline to end-of-study visits in the birch (and related allergens) titrated SPT mean wheal diameter AUC | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Up to 253 Days | 
| Percent change from pre-treatment baseline to end-of-season visits in the birch (and related allergens) titrated SPT mean wheal diameter AUC | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Up to 253 Days | 
| Percent change from pre-treatment baseline to end-of-study visits in the birch (and related allergens) titrated SPT mean wheal diameter AUC | Skin prick test using serial dilutions of birch and related allergens will be evaluated as a percent change from baseline AUC. | Up to 253 Days | 
| Mean of the total Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) score during BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| Mean of the total Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) score during peak BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| RQLQ(S) averaged during the BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal /eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| RQLQ(S) averaged during the peak BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal /eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| Change from baseline in the average RQLQ(S) score during BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal /eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| Change from baseline in the average RQLQ(S) score during peak BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal /eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| Percent change from baseline in the average RQLQ(S) score during BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal /eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to end of BPS, Up to 127 Days | 
| Percent change from baseline in the total RQLQ[S]) score during peak BPS | The RQLQ(S) is a self-administered questionnaire to measure health-related quality of life in those 12 years of age and above, as a result of perennial or seasonal allergic rhinitis. There are 28 items with 1-week recall on the RQLQ(S) in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal /eye symptoms, practical problems, and emotional function. Higher scores indicated more health-related quality of life impairment (lower scores were better). | Up to 253 Days | 
| Incidence rates of Treatment-Emergent Adverse Events (TEAEs) over the study duration |  | Up to 253 Days | 
| Incidence rates of Serious TEAEs through end of study |  | Up to 253 Days | 
| Serum concentration of REGN5713 over the study duration |  | Up to 253 Days | 
| Serum concentration of REGN5714 over the study duration |  | Up to 253 Days | 
| Serum concentration of REGN5715 over the study duration |  | Up to 253 Days | 
| Incidence of anti-drug antibodies (ADA) to REGN5713 over time |  | Up to 253 Days | 
| Incidence of ADA to REGN5714 over time |  | Up to 253 Days | 
| Incidence of ADA to REGN5715 over time |  | Up to 253 Days | 
| Titers of anti-drug antibodies (ADA) to REGN5713 over time |  | Up to 253 Days | 
| Titers of ADA to REGN5714 over time |  | Up to 253 Days | 
| Titers of ADA to REGN5715 over time |  | Up to 253 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Birch Allergy, Birch Pollen Season, Monoclonal antibody(ies), Oak Pollen Season, Subcutaneous immunotherapy, Skin Prick Test