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

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

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)

Study Overview

• Status: Completed
• Conditions: Conjunctivitis; Allergic Rhinitis
• Intervention / Treatment: Other: Placebo; Drug: REGN5713; Drug: REGN5714; Drug: REGN5715

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Health Research Institute
    • Mississauga, Ontario, Canada, L4W 1A4
      • Inflamax Research Limited DBA Cliantha Research
  • Quebec
    • Quebec City, Quebec, Canada, G1V4W2
      • Clinique Spécialisée en Allergie de la Capitale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

1. Documented or participant-reported history of birch tree pollen-triggered allergic-rhinitis (AR) symptoms with or without conjunctivitis (for at least 2 seasons)
2. 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
3. Positive allergen-specific immunoglobulin E (sIgE) tests for birch tree pollen and Bet v 1 (≥0.7 kUa/L) in screening period
4. Demonstrated TNSS ≥ 6 out of 12 on at least 2 time points during the birch EEU exposure challenge in screening period

Key Exclusion Criteria:

1. Participation in a prior REGN5713-5714-5715 clinical trial and received REGN5713-5714-5715 antibodies (receipt of placebo in a previous trial is allowed)
2. 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
3. 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)
4. 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.
5. History of significant, recurrent sinusitis, defined as at least 3 episodes requiring antibiotic treatment per year for the last 2 years
6. Abnormal lung function as judged by the investigator with Forced Expiratory Volume (FEV1) <75% of predicted at screening or randomization
7. 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.
8. History of birch or other tree allergen immunotherapy in the 3 years prior to screening.
9. 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.
10. Allergen-specific immunotherapy with any allergen other than birch or other trees at screening.
11. History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, or neurological disease,
12. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Nasal Symptom Score (TNSS) (2 to 6 Hours) During Out-of-season Birch Allergen Environmental Exposure Unit (EEU) Challenge (REGN5713-5714-5715 vs. Placebo) at Day 29	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome.	Day 29 from randomization (Out-of-season)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean TNSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge (Except for REGN5713-5714-5715) at Day 29	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome.	Day 29 from randomization (Out-of-season)
Mean TNSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Day 57 and Day 85	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome.	Day 57 and Day 85, from randomization (Out-of-season)
Mean Total Ocular Symptom Score (TOSS) (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Day 29	TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome.	Day 29 from randomization (Out-of-season)
Mean TOSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Day 57 and Day 85	TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome.	Day 57 and Day 85, from randomization (Out-of-season)
Mean Total Symptom Score (TSS) (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Day 29	TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome	Day 29 from randomization (Out-of-season)
Mean TSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Day 57 and at Day 85	TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome	Day 57 and Day 85, from randomization (Out-of-season)
Change From Pre-treatment Baseline in TNSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Days 29, 57 and 85	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Change From Pre-treatment Baseline in TOSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Days 29, 57 and 85	TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Change From Pre-treatment Baseline in TSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Days 29, 57 and 85	TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Percent Change From Pre-treatment Baseline in TNSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Days 29, 57 and 85	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Percent Change From Pre-treatment Baseline in TOSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Days 29, 57 and 85	TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Percent Change From Pre-treatment Baseline in TSS (2 to 6 Hours) During Out-of-season Birch Allergen EEU Challenge at Days 29, 57 and Day 85	TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Change From Pre-treatment Baseline in the Birch Titrated Skin Prick Test (SPT) Mean Wheal Diameter Area Under the Curve (AUC) at Day 29	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 29 from randomization (Out-of-season)
Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 57 and Day 85	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 57 and Day 85, from randomization (Out-of-season)
Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 127	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 127 from randomization
Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 225 and Day 253	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 225 from randomization (end-of-season) and Day 253 from randomization (end of study)
Percent Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 29	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 29 from randomization (Out-of-season)
Percent Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 57 and Day 85	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 57 and Day 85, from randomization (Out-of-season)
Percent Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 127	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 127 from randomization
Percent Change From Pre-treatment Baseline in the Birch Titrated SPT Mean Wheal Diameter AUC at Day 225 and Day 253	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 225 from randomization (end-of-season) and Day 253 from randomization (end of study)
Mean TNSS, TOSS and TSS (2 to 6 Hours) During Out-of-season Oak Allergen EEU Challenge at Day 36	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome.	Day 36 from randomization (Out-of-season)
Change From Pre-treatment Baseline in TNSS, TOSS and TSS (2 to 6 Hours) During Oak Allergen EEU Challenge at Day 36	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome.	Day 36 from randomization (Out-of-season)
Percent Change From Pre-treatment Baseline in TNSS, TOSS and TSS (2 to 6 Hours) During Oak Allergen EEU Challenge at Day 36	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome.	Day 36 from randomization (Out-of-season)
Number of Participants Achieving Different Degrees of Clinical Responses Compared Across TNSS (2 to 6 Hours) Response Thresholds	TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Number of Participants Achieving Different Degrees of Clinical Responses Compared Across TOSS (2 to 6 Hours) Response Thresholds	TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Number of Participants Achieving Different Degrees of Clinical Responses Compared Across TSS (2 to 6 Hours) Response Thresholds	TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Number of Participants Achieving Different Degrees of Responses in the Birch Titrated SPT Mean Wheal Diameter AUC Compared Across Different Response Thresholds	Titrated skin prick test (SPT) AUC= The skin prick test mean wheal diameters [mm] using serial dilutions of the allergen were used to calculate an AUC. AUC of titrated SPT mean wheal diameters were derived using the trapezoidal rule. For each participant, the AUC was calculated for the mean wheal diameter calculated over titrated concentrations of the allergen on a log scale and then normalized.	Day 29, Day 57 and Day 85, from randomization (Out-of-season)
Mean TNSS, TOSS and TSS (2 to 6 Hours) During Peak-season Birch Allergen EEU Challenge at Day 190	Peak season EEU is an in-season challenge corresponding to approximate timing of the anticipated peak BPS; TNSS ranges from 0 (none) to 12 (severe): sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale ranging from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): sum of 2 eye symptoms graded on a Likert scale each ranging from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): sum of TNSS & TOSS combined; Higher score indicates worse outcome.	Day 190 from randomization (In-season); Timing may vary based on local season
Daily Averaged TNSS, TOSS, TSS, Daily Medication Score (DMS) and Combined Symptom and Medication Score (CSMS) During Birch Pollen Season (BPS)	TNSS ranges from 0 (none) to 12 (severe): Sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): Sum of 2 eye symptoms graded on Likert scale each from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): Sum of TNSS & TOSS; Higher score indicates worse outcome. DMS ranges from 0 to 20 (max points): Sum for each pre-specified medication taken as oral antihistamine 6 points/dose (max daily score 6), ocular antihistamine 1.5 points/drop (max daily score 6), intranasal corticosteroid 2.0 points/spray (max daily score 8). CSMS ranges from 0 to 38 (max): Sum of DMS & TSS higher score indicates worse outcome). Daily TNSS, TOSS, TSS, DMS & CSMS each averaged over duration of birch pollen season presented.	Up to 253 days from randomization (during BPS)
Daily Averaged TNSS, TOSS, TSS, DMS and CSMS During Peak BPS	TNSS ranges from 0 (none) to 12 (severe): Sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): Sum of 2 eye symptoms graded on Likert scale each from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): Sum of TNSS & TOSS; Higher score indicates worse outcome. DMS ranges from 0 to 20 (max points): Sum for each pre-specified medication taken as oral antihistamine 6 points/dose (max daily score 6), ocular antihistamine 1.5 points/drop (max daily score 6), intranasal corticosteroid 2.0 points/spray (max daily score 8). CSMS ranges from 0 to 38 (max): Sum of DMS & TSS higher score indicates worse outcome). Daily TNSS, TOSS, TSS, DMS & CSMS each averaged over duration of peak birch pollen season presented.	Up to 253 days from randomization (during peak BPS)
Change From Pre-treatment Baseline in TNSS, TOSS, TSS, DMS and CSMS Averaged During BPS	TNSS ranges from 0 (none) to 12 (severe): Sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on a Likert scale from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): Sum of 2 eye symptoms graded on Likert scale each from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): Sum of TNSS & TOSS; Higher score indicates worse outcome. DMS ranges from 0 to 20 (max points): Sum for pre-specified medication taken as oral antihistamine 6 points/dose (max daily score 6), ocular antihistamine 1.5 points/drop (max daily score 6), intranasal corticosteroid 2.0 points/spray (max daily score 8). CSMS ranges from 0 to 38 (max): Sum of DMS & TSS; Higher score indicates worse outcome. Change from pre-treatment baseline in TNSS, TOSS, TSS, DMS & CSMS each averaged over duration of birch pollen season presented.	Up to 253 days from randomization (during BPS)
Change From Pre-treatment Baseline in TNSS, TOSS, TSS, DMS and CSMS Averaged During Peak BPS	TNSS ranges from 0 (none) to 12 (severe): Sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on Likert scale from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS ranges from 0 (none) to 6 (severe): Sum of 2 eye symptoms graded on Likert scale each from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS ranges from 0 (none) to 18 (severe): Sum of TNSS & TOSS; Higher score indicates worse outcome. DMS ranges from 0 to 20 (max points): Sum for pre-specified medication taken as oral antihistamine 6 points/dose (max daily score 6), ocular antihistamine 1.5 points/drop (max daily score 6), intranasal corticosteroid 2.0 points/spray (max daily score 8). CSMS ranges from 0 to 38 (max): Sum of DMS & TSS; Higher score indicates worse outcome. Change from pre-treatment baseline in TNSS, TOSS, TSS, DMS & CSMS each averaged over duration of peak birch pollen season presented.	Up to 253 days from randomization (during peak BPS)
Percent Change From Pre-treatment Baseline in TNSS, TOSS, TSS, DMS and CSMS Averaged During BPS	TNSS range from 0 (none) to 12 (severe): Sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on Likert scale from 0 (none) to 3 (severe); Higher score indicates worse outcome. TOSS range from 0 (none) to 6 (severe): Sum of 2 eye symptoms graded on Likert scale each from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering; Higher score indicates worse outcome. TSS range from 0 (none) to 18 (severe): Sum of TNSS & TOSS; Higher score indicates worse outcome. DMS range from 0 to 20 (max points): Sum for pre-specified medication taken as oral antihistamine 6 points/dose (max daily score 6), ocular antihistamine 1.5 points/drop (max daily score 6), intranasal corticosteroid 2.0 points/spray (max daily score 8). CSMS range from 0 to 38 (max): Sum of DMS & TSS; Higher score indicates worse outcome. Percent change from pre-treatment baseline in TNSS, TOSS, TSS, DMS & CSMS each averaged over duration of birch pollen season presented.	Up to 253 days from randomization (during BPS)
Percent Change From Pre-treatment Baseline in TNSS, TOSS, TSS, DMS and CSMS Averaged During Peak BPS	TNSS range from 0 (none) to 12 (severe): Sum of 4 nasal symptoms (nasal congestion, itching, & runny nose, & sneezing) graded on Likert scale from 0 (none) to 3 (severe);Higher score indicates worse outcome. TOSS range from 0 (none) to 6 (severe): Sum of 2 eye symptoms graded on Likert scale each from 0 (none) to 3 (severe) for itching/redness/gritty feeling & tearing/watering;Higher score indicates worse outcome. TSS range from 0 (none) to 18 (severe): Sum of TNSS & TOSS;Higher score indicates worse outcome. DMS range from 0 to 20 (max points): Sum for pre-specified medication taken as oral antihistamine 6 points/dose (max daily score 6), ocular antihistamine 1.5 points/drop (max daily score 6), intranasal corticosteroid 2.0 points/spray (max daily score 8). CSMS range from 0 to 38 (max): Sum of DMS & TSS;Higher score indicates worse outcome. Percent change from pre-treatment baseline in TNSS, TOSS, TSS, DMS & CSMS each averaged over duration of peak birch pollen season presented.	Up to 253 days from randomization (during peak BPS)
Standardized Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) Score Averaged 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 in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function with responses based on a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). Overall RQLQ(S) score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. Higher scores indicate more health-related quality of life impairment (lower scores are better). Overall RQLQ(S) score averaged over duration of birch pollen season presented.	Up to 253 days from randomization (during BPS)
Standardized RQLQ(S) Score Averaged 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 in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function with responses based on a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). Overall RQLQ(S) score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. Higher scores indicate more health-related quality of life impairment (lower scores are better). Overall RQLQ(S) score averaged over duration of peak birch pollen season presented.	Up to 253 days from randomization (during peak BPS)
Change From Pre-treatment 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 in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function with responses based on a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). Overall RQLQ(S) score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. Higher scores indicate more health-related quality of life impairment (lower scores are better). Change from pre-treatment baseline averaged over duration of birch pollen season presented.	Up to 253 days from randomization (during BPS)
Change From Pre-treatment 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 in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function with responses based on a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). Overall RQLQ(S) score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. Higher scores indicate more health-related quality of life impairment (lower scores are better). Change from pre-treatment baseline averaged over duration of peak birch pollen season presented.	Up to 253 days from randomization (during peak BPS)
Percent Change From Pre-treatment 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 in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function with responses based on a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). Overall RQLQ(S) score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. Higher scores indicate more health-related quality of life impairment (lower scores are better). Percent change from pre-treatment baseline averaged over duration of birch pollen season presented.	Up to 253 days from randomization (during BPS)
Percent Change From Pre-treatment 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 in 7 domains: activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems, and emotional function with responses based on a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). Overall RQLQ(S) score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. Higher scores indicate more health-related quality of life impairment (lower scores are better). Percent change from pre-treatment baseline averaged over duration of peak birch pollen season presented.	Up to 253 days from randomization (during peak BPS)
Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) Over the Study Duration		Up to 253 Days
Number of Participants With Any Treatment-Emergent Serious AE (TESAE) Over the Study Duration		Up to 253 Days
Serum Concentration of REGN5713 Over the Study Duration		Up to Week 36
Serum Concentration of REGN5714 Over the Study Duration		Up to Week 36
Serum Concentration of REGN5715 Over the Study Duration		Up to Week 36
Number of Participants With Anti-drug Antibodies (ADA) to REGN5713 Over Time		Up to Week 36
Number of Participants With ADA to REGN5714 Over Time		Up to Week 36
Number of Participants With ADA to REGN5715 Over Time		Up to Week 36

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2022
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: June 20, 2022
• First Submitted That Met QC Criteria: June 20, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Skin Prick Test; Subcutaneous immunotherapy; Birch Allergy; Birch Pollen Season; Monoclonal antibody(ies); Oak Pollen Season
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Eye Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Nose Diseases; Otorhinolaryngologic Diseases; Conjunctival Diseases; Conjunctivitis; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: R5713-5714-5715-ALG-21111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency [EMA], Pharmaceuticals and Medical Devices Agency [PMDA], etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes