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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Regeneron Study Site
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Regeneron Study Site
• Canada
  • Quebec, Canada, G1V 4M6
    • Regeneron Study Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Regeneron Study Site
    • London, Ontario, Canada, N5W 6A2
      • Regeneron Study Site
    • Ottawa, Ontario, Canada, K1G 6C6
      • Regeneron Study Site
    • Toronto, Ontario, Canada, M4V 1R2
      • Regeneron Study Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Regeneron Study Site
    • Toronto, Ontario, Canada, M5G 1E2
      • Regeneron Study Site
  • Quebec
    • Trois-Rivieres, Quebec, Canada, G8T 7A1
      • Regeneron Study Site
• Denmark
  • Capital
    • Hvidovre, Capital, Denmark, 2650
      • Regeneron Study Site
  • Copenhagen Surroundings
    • Hellerup, Copenhagen Surroundings, Denmark, 2900
      • Regeneron Study Site
  • South Jutland
    • Vejle, South Jutland, Denmark, 7100
      • Regeneron Study Site
• Germany
  • Berlin, Germany, 10117
    • Regeneron Study Site
  • Berlin, Germany, 14050
    • Regeneron Study Site
  • Hamburg, Germany, 22549
    • Regeneron Study Site
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • Regeneron Study Site
    • Stuttgart, Baden-Wurttemberg, Germany, 70374
      • Regeneron Study Site
  • Hessen
    • Dreieich, Hessen, Germany, 63303
      • Regeneron Study Site
    • Wiesbaden, Hessen, Germany, 65183
      • Regeneron Study Site
  • Nordrhein-Westfalen
    • Duisburg, Nordrhein-Westfalen, Germany, 47051
      • Regeneron Study Site
  • North Rhine-Westphalia
    • Dusseldorf, North Rhine-Westphalia, Germany, 40225
      • Regeneron Study Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01139
      • Regeneron Study Site
• United States
  • Maine
    • Bangor, Maine, United States, 04401
      • Regeneron Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Regeneron Study Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Regeneron Study Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Regeneron Study Site
    • Saint Louis, Missouri, United States, 63141
      • Regeneron Study Site
  • Montana
    • Missoula, Montana, United States, 59808
      • Regeneron Study Site
  • New Jersey
    • Verona, New Jersey, United States, 07044
      • Regeneron Study Site
  • New York
    • Great Neck, New York, United States, 11021
      • Regeneron Study Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Regeneron Study Site
    • Toledo, Ohio, United States, 43617
      • Regeneron Study Site
  • Oregon
    • Portland, Oregon, United States, 97202
      • Regeneron Study Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • Regeneron Study Site
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Regeneron Study Site
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria

1. Documented or participant-reported history of birch pollen-triggered allergic rhinitis symptoms, with or without conjunctivitis, for at least 2 years
2. Positive Skin prick test (SPT) with birch pollen extract in the screening period, as defined in the protocol
3. Positive Allergen-specific IgE (sIgE) tests for birch pollen and Bet v 1 in the screening period, as defined in the protocol
4. Willing and able to comply with clinic visits and study-related procedures

Key Exclusion Criteria:

1. Participation in a prior REGN5713-5714-5715 clinical trial
2. 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
3. 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
4. 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
5. Documentation of active SARS-CoV-2 infection, as defined in the protocol
6. A clinical history of asthma with 2 or more asthma exacerbations requiring hospitalizations or systemic corticosteroids in the previous year
7. History of birch allergy immunotherapy as defined in the protocol
8. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN5713-5714-5715; REGN5713-5714-5715 administered subcutaneously	Drug: REGN5713; Administered subcutaneously; Drug: REGN5714; Administered subcutaneously; Drug: REGN5715; Administered subcutaneously
Placebo Comparator: Placebo Only; Placebo matching REGN5713-5714-5715 administered subcutaneously	Drug: Placebo; Placebo that replaces REGN5713-5714-5715

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Actual): August 24, 2021
• Study Completion (Actual): August 24, 2021

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Birch Allergy
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Conjunctival Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Conjunctivitis
• Other Study ID Numbers: R5713-5714-5715-ALG-2001; 2020-004094-52 (EudraCT Number)

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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No