Study to Assess the Efficacy of Anti-Bet v 1 Monoclonal Antibodies in Adults to Reduce Symptoms of Seasonal Allergic Rhinitis

Study Overview
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Brief Summary
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The primary objective is to assess the reduction of allergic symptoms as measured by combined symptom and medication score (CSMS) during birch pollen season after a single dose of REGN5713-5714-5715 versus placebo.

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy of Anti-Bet v 1 Monoclonal Antibodies to Reduce Symptoms of Seasonal Allergic Rhinitis

Conditions
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Allergic Rhinitis, Conjunctivitis

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Documented or participant-reported history of birch pollen-triggered allergic rhinitis symptoms, with or without conjunctivitis, for at least 2 years Positive Skin prick test (SPT) with birch pollen extract in the screening period, as defined in the protocol Positive Allergen-specific IgE (sIgE) tests for birch pollen and Bet v 1 in the screening period, as defined in the protocol Willing and able to comply with clinic visits and study-related procedures Key Exclusion Criteria: Participation in a prior REGN5713-5714-5715 clinical trial Recurrent or chronic rhinitis or sinusitis not associated with birch pollen season, or due to daily contact with other allergens causing symptoms that are expected to coincide with birch pollen season, as assessed by the investigator Participants who anticipate major changes in allergen exposure in their home or work environments that are expected to coincide with the study assessments as assessed by the investigator Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections (at the discretion of the investigator) within 4 weeks prior to screening visit. Participants may be re-evaluated for eligibility after symptoms resolve Documentation of active SARS-CoV-2 infection, as defined in the protocol A clinical history of asthma with 2 or more asthma exacerbations requiring hospitalizations or systemic corticosteroids in the previous year History of birch allergy immunotherapy as defined in the protocol Use of anti-IgE or other biological therapy in treatment of asthma or allergy within 6 months prior to screening 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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No

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>REGN5713-5714-5715 administered subcutaneously | Drug: REGN5713<br>* Administered subcutaneously<br>Drug: REGN5714<br>* Administered subcutaneously<br>Drug: REGN5715<br>* Administered subcutaneously<br>|
| Placebo Comparator: Placebo Only<br>Placebo matching REGN5713-5714-5715 administered subcutaneously | Drug: Placebo<br>* Placebo that replaces REGN5713-5714-5715<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Symptom and Medication Score (CSMS) in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | The average CSMS will be calculated based on daily symptom score and daily medication score recorded over the duration of the birch pollen season (BPS). CSMS is calculated by adding the Daily Medication Score (DMS) and Total Symptom Score (TSS) together, with scores ranging between 0 (none) and 38 (severe). | Until the end of Birch Pollen Season, up to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Symptom Score (TSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | TSS is a combined score of TOSS and TNSS. TNSS and TOSS are scored as in part 1 each for a combined TSS of 0 (none) to 18 (severe) | Until the end of Birch Pollen Season, up to Week 16 | 
| Total Nasal Symptom Score (TNSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Total nasal symptom score (TNSS) is 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 congestion, itching, and rhinorrhea, and from 0 (none) to 3 (5 or more sneezes) for sneezing. | Until the end of Birch Pollen Season, up to Week 16 | 
| Total Ocular Symptom Score (TOSS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Total ocular symptom score is 0 to 6 and is based on itching/redness/gritty feeling and tearing/watering; each of the 2 symptoms is graded 0 (absent), 1 (mild), 2 (moderate), and 3 (severe) | Until the end of Birch Pollen Season, up to Week 16 | 
| Daily Medication Score (DMS), Averaged Over the Duration of the Birch Pollen Season, in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | The Daily Medication Score (DMS) is calculated by adding points for each pre-specified medication taken as follows: desloratadine 5 mg 6 points/dose; maximum daily score 6 points, olopatadine 1 mg/mL each drop 1.5 points/drop; maximum daily score 6 points, mometasone furoate 50 ug/dose 2.0 points/spray; maximum daily score 8 points). The scale is 0 (minimum) to 20 (maximum) | Until the end of Birch Pollen Season, up to Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Throughout the Study | Number of participants with any Treatment Emergent Adverse Events (TEAEs) from participating in study | Up to Day 127 | 
| Number of Participants With Serious TEAEs Throughout the Study | Number of participants with any Serious Treatment Emergent Adverse Events (TEAEs) from participating in study | Up to Day 127 | 
| Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo | Number of participants who showed change from baseline to the end of the study in Birch Skin Prick Test (SPT) Mean Wheal Diameter, in participants who received REGN5713-5714-5715 compared to placebo | Baseline through Day 127 | 
| Percent Change From Baseline to the End of Study in Birch SPT Mean Wheal Diameter in Participants Who Receive a Single Dose of REGN5713-5714-5715 Versus Placebo |  | Baseline through Day 127 | 
| Serum Concentration of REGN5713 Over the Study Duration |  | Day 0, Day 56, Day 112 | 
| Serum Concentration of REGN5714 Over the Study Duration |  | Up to Day 127 | 
| Serum Concentration of REGN5715 Over the Study Duration |  | Up to Day 127 | 
| Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5713 Throughout the Study | Percentage of participants who developed antibodies to intervention provided during study | Up to Day 127 | 
| Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5714 Throughout the Study | Percentage of participants who developed antibodies to intervention provided during study | Up to Day 127 | 
| Percentage of Participants With Treatment Emergent Anti-drug Antibodies to REGN5715 Throughout the Study | Percentage of participants who developed antibodies to intervention provided during study | Up to Day 127 | 
| Number of Well Days | Well Days are defined as days when rescue medication is not utilized and the Total symptom score (TSS) is ≤2/18 | Until the end of Birch Pollen Season, up to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Birch Allergy