Study in Cat-Allergic Patients With Asthma to Evaluate the Efficacy of a Single Dose of REGN1908-1909 to Reduce Bronchoconstriction Upon Cat Allergen Challenge

Study Overview
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Brief Summary
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The primary objective is to evaluate the prophylactic efficacy of REGN1908-1909 (anti-Fel d 1) administered as a single dose on day 1 in cat-allergic asthmatic patients not living with a cat in the prevention of a Controlled Cat Allergen Challenge-induced early asthmatic response (EAR) assessed by measures of lung function (FEV1) compared to placebo-treated patients. Secondary Efficacy Objectives: To evaluate the prophylactic efficacy of REGN1908-1909 administered as a single dose on day 1 in cat-allergic asthmatic patients not living with a cat, in the prevention of a Controlled Cat Allergen Challenge-induced: Allergic rhinitis and Ocular symptoms To evaluate the prophylactic efficacy of REGN1908-1909 administered as a single dose on day 1 in cat-allergic asthmatic patients not living with a cat to increase the exposure to cat allergen, measured as a product of minute ventilation and time, required to induce EAR in a Controlled Cat Allergen Challenge as compared to placebo patients Secondary Safety Objective: To evaluate the safety and tolerability of REGN1908-1909 vs. placebo in patients with cat allergen-triggered asthma

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study in Cat-Allergic Patients With Asthma to Evaluate the Efficacy of a Single Dose of REGN1908-1909 to Reduce Bronchoconstriction Upon Cat Allergen Challenge

Conditions
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Cat Allergy, Mild Asthma

Intervention / Treatment
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* Drug: REGN1908-1909
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented or patient reported history (for at least 2 years) of symptomatic cat allergen-triggered asthma with rhinitis with or without conjunctivitis No cat exposure at home for the past year and must continue having no exposure at home during the study; cat exposure outside of the home shall be avoided for at least one week prior to any Cat Allergen Challenge and during the defined follow-up period Less than 10 pack-years of smoking history Key Exclusion Criteria: Positive human immunodeficiency virus (HIV) test Positive hepatitis test (HBsAg and hepatitis C antibody) History of significant multiple and/or severe allergies (including latex gloves) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food Participation in a prior REGN1908-1909 clinical trial History of severe anaphylactic or severe asthmatic reactions to cat exposure Active lung disease other than asthma Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening Persistent chronic or recurring acute infection requiring treatment with antibiotics, antivirals, or antifungals, or any untreated respiratory infections within 4 weeks prior to screening History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures Treatment of asthma requiring systemic (oral or parenteral) corticosteroid treatment more than twice within 12 months or once within 3 months prior to screening or has been hospitalized or has attended the ER/Urgent Care facility for asthma more than twice in prior 12 months before screening. History of hypersensitivity to corticosteroids or antihistamines, or drug treatment excipient Note: Other protocol defined Inclusion/Exclusion Criteria Apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: REGN1908-1909<br> | Drug: REGN1908-1909<br>* Single subcutaneous (SC) dose of REGN1908 and REGN1909<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single subcutaneous (SC) dose of matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8 | Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the participant voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms. | Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 | Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the participant voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms | Days 29, 57 and 85 | 
| Percent Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 AUC as a continuous covariate. | Days 8, 29, 57, and 85 | 
| Change in Normalized Area Under the Curve (AUC) of Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge Over Exposure Interval From Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 AUC as a continuous covariate. | Days 8, 29, 57, and 85 | 
| Change From Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Individual nasal symptoms, including rhinorrhea, nasal congestion, nasal itching, and sneezing were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the Total Nasal Symptom Score (TNSS) with a maximum score of 12. Scale range is 0-12. The higher the score, the more severe the symptoms. | Days 8, 29, 57 and 85 | 
| Change From Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge Over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85 | Individual ocular symptoms for itching/burning, redness, swelling/puffiness, and tearing/watery eyes were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the TOSS, with a maximum score of 12. Score range is 0-12. The higher the score, the more severe the symptoms. | Days 8, 29, 57 and 85 | 
| Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate. | Days 8, 29, 57 and 85 | 
| Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 | Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate. | Days 8, 29, 57 and 85 | 
| Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | Adverse events and serious adverse events were collected from the time of informed consent signature and then at each visit until the end of the study with the exception of symptoms that occurred in response to the EEU within 24 hours following the EEU. | Baseline to 16 weeks |