A Study to Examine the Efficacy and Safety of Anti-Fel d 1 Antibodies Injections in Cat-allergic Adolescent and Adult Patients With Allergic Rhinitis Who Live With a Cat

Study Overview
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Brief Summary
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The primary objective of the study is to determine the efficacy of REGN1908-1909, as compared to placebo, to reduce allergic rhinitis/conjunctivitis symptoms and allergy rescue medication use during natural cat exposure. The Secondary Objectives are: To assess the reduction of allergic symptoms and use of allergy rescue medications after treatment with REGN1908-1909 versus placebo, as measured by the individual components of the CSMS To assess health-related quality of life (HRQoL) as measured by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) To determine the efficacy of REGN1908-1909, as compared to placebo, to inhibit a wheal-and-flare response to a skin prick test with cat allergen To assess the durability of effect in allergic rhinitis and conjunctivitis symptom and medication scores after multiple doses of REGN1908-1909 compared to placebo given every 12 weeks (Q12W) To determine the efficacy following multiple doses of REGN1908-1909 compared to placebo at inhibiting a wheal-and-flare response to a skin prick test with cat allergen To estimate the effect of REGN1908-1909 on lung function, as compared to placebo, in patients with asthma To determine the efficacy of REGN1908-1909 as compared to placebo to reduce asthma symptoms in patients with asthma To assess whether there is a difference in asthma rescue medication use in patients with asthma who are treated with REGN1908-1909 compared to placebo To assess whether there is a difference in nighttime awakenings in patients with asthma treated with REGN1908-1909 compared to placebo To evaluate the short-term and long-term safety and tolerability of REGN1908-1909, including the incidence of hypersensitivity reactions, local injection site reactions, and asthma exacerbations To determine systemic exposure of total (free and antigen-bound) antibodies as measured by concentration of REGN1908 and REGN1909 To assess the immunogenicity of REGN1908 and REGN1909

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study in Cat-Allergic Patients With Allergic Rhinitis Who Live With a Cat to Assess the Efficacy and Safety of Anti-Fel d 1 Antibodies During Natural Cat Exposure in the Home

Conditions
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Allergic Rhinitis Due to Cat Allergy

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Generally healthy males and females who are 12 years and older at the time of screening. Weight must be ≥40 kg at the time of screening Documented or patient reported history (for at least 2 years) of symptomatic cat allergen-triggered allergic rhinitis with or without conjunctivitis and with or without asthma as defined by all of the following criteria: Positive skin prick test (SPT) with cat hair extract (mean wheal diameter at least 5 mm greater than a negative control) at screening Positive allergen-specific IgE (sIgE) tests for cat and Fel d 1 (both ≥0.7 kUa/L at screening) Documented or patient reported history of nasal and/or ocular symptoms upon cat exposure Symptomatic despite the use of medications to treat their nasal and/or ocular symptoms At least 1 generally healthy cat (that is unlikely to die during the study) living in the home resulting in regular exposure A daily total rhinitis/conjunctivitis symptom score (total symptom score [TSS]) of at least 8 of 18 during at least 8 days of the 15-day baseline assessment period and use of standard, therapeutic doses of pharmacotherapy for the treatment of allergic rhinoconjunctivitis on at least 8 days of the 15-day baseline assessment period. Key Exclusion Criteria: History of significant multiple and/or severe allergies, as assessed by the investigator, that would potentially interfere with the assessments during the baseline and 12-week efficacy assessment periods or confound results, per investigator discretion, including significant rhinitis or sinusitis due to daily contact with other allergens causing symptoms that are expected to coincide with the baseline period or any of the efficacy assessment periods Received REGN1908-1909 in a prior REGN1908-1909 clinical trial (receipt of placebo in a previous trial is allowed) Active lung disease other than asthma FEV1 less than 70% of predicted at screening or randomization 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. Patients may be re-evaluated after resolution of symptoms and specified time duration NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Ages Eligible for Study
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Minimum Age: 12 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>Randomized 1:1 | Drug: REGN1908-1909<br>* Subcutaneous (SC) for a total of 5 administrations<br>|
| Placebo Comparator: Placebo<br>Randomized 1:1 | Drug: Matching Placebo<br>* SC for a total of 5 administrations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily combined symptom and medication score (CSMS) averaged over last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo. | 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). | Weeks 48 to 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily total nasal symptom score (TNSS) averaged over the last 12 weeks of treatment period in patients who receive REGN1908-1909 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. | Weeks 48 to 60 | 
| Percent change from pre-treatment baseline in average CSMS over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Percent change from pre-treatment baseline in average TNSS over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Daily total symptom score (TSS) averaged over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 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) | Weeks 48 to 60 | 
| Percent change from pre-treatment baseline in average TSS over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Percent change from baseline to the end of treatment in cat skin prick test (SPT) mean wheal diameter in patients who receive REGN1908-1909 versus placebo |  | Week 60 | 
| Daily CSMS averaged over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Daily TNSS averaged over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Percent change from pre-treatment baseline in average CSMS over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Percent change from pre-treatment baseline in average TNSS over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Percent change from pre-treatment baseline in average TSS over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Daily TSS score averaged over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Percent change from pre-treatment baseline in average TOSS, over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 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) | Weeks 0 to 12 | 
| Daily TOSS averaged over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Percent change from pre-treatment baseline in average TOSS over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Percent change in forced expiratory volume (FEV)1 in patients with asthma who receive REGN1908-1909 versus placebo |  | Baseline to week 12 | 
| Percent change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo |  | Baseline to week 60 | 
| Percent change in cat SPT mean wheal diameter in patients who receive REGN1908-1909 versus placebo |  | Baseline to week 12 | 
| Change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo |  | Baseline to week 12 | 
| Change in FEV1 in patients with asthma who receive REGN1908-1909 versus placebo |  | Baseline to week 60 | 
| Change in Rhinoconjunctivitis Quality of Life Questionnaire for Ages 12+ (RQLQ(S)+12) in patients who receive REGN1908-1909 versus placebo | The RQLQ has 25 questions in 6 domains (nose symptoms, eye symptoms, practical problems, activity limitation, non-hay fever symptoms and emotional function). Patients recall how they have been during the previous week and respond to each question on a 7-point scale. The overall RQLQ score is the mean of all 25 responses and the individual domain scores are the means of the items in those domains. | Baseline to week 60 | 
| Daily medication score (DMS) averaged over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo | The Daily Medication Score (DMS) is calculated by adding points for each pre-specified medication. The scale is 0 (minimum) to 20 (maximum) | Weeks 0 to 12 | 
| DMS averaged over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Percent change from pre-treatment baseline in average DMS averaged over the last 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Percent change in cat SPT mean wheal diameter in patients who receive REGN1908-1909 versus placebo |  | Baseline to week 72 | 
| Asthma daily symptom (ADS) score, averaged over the initial 12 weeks of the treatment period using Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) in patients with asthma who receive REGN1908-1909 versus placebo | The total daily asthma symptom score is a patient-reported outcome concerning the occurrence of asthma symptoms and their effect on a patient's daily activities and sleep. It is composed of two parts: daytime (five items) and nighttime (four items), both scored ordinally. Higher scores indicate more severe symptoms. | Weeks 0 to 12 | 
| ADS score averaged over the last 12 weeks of the treatment period using ADSD and the ANSD in patients with asthma who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Daily TOSS averaged over the initial 12 weeks of the treatment period in patients who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Change from baseline to week 60 in Asthma Control Questionnaire 5 Question Version (ACQ-5) in patients with asthma who receive REGN1908-1909 versus placebo | The ACQ-5 had 5 questions, reflecting the top-scoring five asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during the previous week and to respond to each of the five symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total mean score was mean of the scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled), higher scores indicated lower asthma control. | Baseline to week 60 | 
| Daily number of nighttime awakenings averaged over the initial 12 weeks of the treatment period in patients with asthma who receive REGN1908-1909 versus placebo |  | Weeks 0 to 12 | 
| Daily number of nighttime awakenings averaged over the last 12 weeks of the treatment period in patients with asthma who receive REGN1908-1909 versus placebo |  | Weeks 48 to 60 | 
| Incidence of treatment-emergent adverse events (TEAEs) throughout the study |  | Weeks 0 to 72 | 
| Incidence of adverse event of special interests (AESIs) throughout the study |  | Weeks 0 to 72 | 
| Incidence of serious TEAEs throughout the study |  | Weeks 0 to 72 | 
| Total REGN1908 concentration in serum over the study duration |  | Weeks 0 to 72 | 
| Total REGN1909 concentration in serum over the study duration |  | Weeks 0 to 72 | 
| Incidence of treatment-emergent anti-drug antibodies (ADAs) to REGN1908 throughout the study |  | Weeks 0 to 72 | 
| Incidence of treatment-emergent ADAs to REGN1909 throughout the study |  | Weeks 0 to 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cat allergy induced allergic rhinitis, Asthma, Allergic conjunctivitis