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

Phase 3TerminatedNCT04981717

Regeneron Pharmaceuticals446 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Generally healthy males and females who are 12 years and older at the time of screening. 2. Weight must be ≥40 kg at the time of screening 3. 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: 1. Positive skin prick test (SPT) with cat hair extract (mean wheal diameter at least 5 mm greater than a negative control) at screening 2. Positive allergen-specific IgE (sIgE) tests for cat and Fel d 1 (both ≥0.7 kUa/L at screening) 3. Documented or patient reported history of nasal and/or ocular symptoms upon cat exposure 4. Symptomatic despite the use of medications to treat their nasal and/or ocular symptoms 4. At least 1 generally healthy cat (that is unlikely to die during the study) living in the home resulting in regular exposure 5. 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: 1. 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 2. Received REGN1908-1909 in a prior REGN1908-1909 clinical trial (receipt of placebo in a previous trial is allowed) 3. Active lung disease other than asthma 4. FEV1 less than 70% of predicted at screening or randomization 5. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening 6. 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

Locations (92)

Allergy and Asthma Associates of Southern California - CRN - PPDS

Mission Viejo, California, United States

Integrated Research of Inland, Inc

Riverside, California, United States

Peninsula Research Associates - CRN - PPDS

Rolling Hills Estates, California, United States

Allergy and Asthma Medical Group and Research Center - CRN - PPDS

San Diego, California, United States

Asthma and Allergy Associates PC - CRN - PPDS

Colorado Springs, Colorado, United States

Outcomes

Primary Outcomes

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).

Time frame: Weeks 48 to 60

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: Week 60

Daily CSMS Averaged Over the Initial 12 Weeks of the Treatment Period in Patients Who Receive REGN1908-1909 Versus Placebo

The combined symptom and medication score (CSMS) is defined as the daily combined allergic rhinitis and conjunctivitis total symptom score (TSS: calculated as the sum of total nasal symptom score \[TNSS\] and total ocular symptom score \[TOSS\]) plus daily medication score (DMS). Scores ranging between 0 (none) and 38 (severe).

Time frame: Weeks 0 to 12

Daily TNSS Averaged Over the Initial 12 Weeks of the Treatment Period in Patients Who Receive REGN1908-1909 Versus Placebo

The TNSS ranges 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 nasal congestion, itching, and runny nose, and sneezing.

Time frame: 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

Time frame: 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

The TNSS ranges 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 nasal congestion, itching, and runny nose, and sneezing.

Time frame: 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

Total symptom score (TSS: calculated as the sum of TNSS and total ocular symptom score \[TOSS\]) plus daily medication score (DMS).

Time frame: 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

Total symptom score (TSS: calculated as the sum of TNSS and total ocular symptom score \[TOSS\]) plus daily medication score (DMS).

Time frame: 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)

Time frame: Weeks 0 to 12

Daily TOSS Averaged Over the Last 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)

Time frame: 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

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)

Time frame: Weeks 48 to 60

Percent Change in Forced Expiratory Volume (FEV)1 in Patients With Asthma Who Receive REGN1908-1909 Versus Placebo

In-clinic spirometry on all patients to determine FEV1 (forced expiratory volume in 1 second) in liters (L).

Time frame: Baseline to week 12

Percent Change in FEV1 in Patients With Asthma Who Receive REGN1908-1909 Versus Placebo

In-clinic spirometry on all patients to determine FEV1 (forced expiratory volume in 1 second) in liters (L).

Time frame: Baseline to week 60

Percent Change in Cat SPT Mean Wheal Diameter in Patients Who Receive REGN1908-1909 Versus Placebo

The full analysis set (FAS) includes all randomized participants; it is based on the treatment allocated (as randomized). Efficacy endpoints will be analyzed using the FAS.

Time frame: Baseline to week 72

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

Time frame: Weeks 0 to 12

Number of Participants With Adverse Event of Special Interests (AESIs) Throughout the Study

Time frame: Weeks 0 to 72

Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs) Throughout the Study

Time frame: Weeks 0 to 60

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Throughout the Study

Time frame: Weeks 0 to 72

Total REGN1908 Concentration in Serum Over the Study Duration

Time frame: Weeks 0 to 60

Total REGN1909 Concentration in Serum Over the Study Duration

Time frame: Weeks 0 to 60

Incidence of Treatment-emergent Anti-drug Antibodies (ADAs) to REGN1908 Throughout the Study

Time frame: Weeks 0 to 72

Incidence of Treatment-emergent ADAs to REGN1909 Throughout the Study

Time frame: Weeks 0 to 72

Percent Change in Cat SPT Mean Wheal Diameter in Patients Who Receive REGN1908-1909 Versus Placebo (up to Week 12)

Time frame: Baseline to week 12

Percent Change in FEV1 in Participants With Asthma Who Receive REGN1908-1909 Versus Placebo (up to Week 12)

Time frame: Baseline to week 12

Percent Change in FEV1 in Participants With Asthma Who Receive REGN1908-1909 Versus Placebo (up to Week 60)

Time frame: Baseline to week 60

Change From Baseline to Week 60 in Rhinoconjunctivitis Quality of Life Questionnaire for Ages 12+ (RQLQ(S)+12) in Participants Who Received REGN1908-1909 Versus Placebo

The RQLQ had 25 questions in 6 domains (nose symptoms, eye symptoms, practical problems, activity limitation, non-hay fever symptoms and emotional function). Participants recalled how they have been during the previous week and responded to each question on a 7-point scale. The overall RQLQ score was the mean of all 25 responses and the individual domain scores were the means of the items in those domains. The RQLQ(S) responses are based on a 7-point Likert scale with responses ranging from 0 (not troubled) to 6 (extremely troubled).

Time frame: Baseline to week 60

Daily Medication Score (DMS) Averaged Over the Initial 12 Weeks of the Treatment Period in Participants Who Receive REGN1908-1909 Versus Placebo

The Daily Medication Score (DMS) was calculated by adding points for each pre-specified medication. Participants will be asked to record their daily rescue medication use using an e-diary, including which medications and the amount of these prespecified medications. The scale is 0 (minimum) to 20 (maximum)

Time frame: Weeks 0 to 12

DMS Averaged Over the Last 12 Weeks of the Treatment Period in Participants Who Receive REGN1908-1909 Versus Placebo

Time frame: Weeks 48 to 60

Percent Change From Pre-treatment Baseline in Average DMS Averaged Over the Last 12 Weeks of the Treatment Period in Participants Who Receive REGN1908-1909 Versus Placebo

Time frame: Weeks 48 to 60

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 Participants With Asthma Who Receive REGN1908-1909 Versus Placebo

The total daily asthma symptom score is a participant-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. The ADSD score will be based on 6 patient-reported symptoms (difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough at their worst using an 11-point numeric rating scale (NRS) ranging from 0 ('None') to 10 ('As bad as you can imagine').

Time frame: Weeks 0 to 12

ADS Score Averaged Over the Last 12 Weeks of the Treatment Period Using ADSD and the ANSD in Participants With Asthma Who Receive REGN1908-1909 Versus Placebo (Weeks 48 to 60)

Time frame: Weeks 48 to 60

Daily TOSS Averaged Over the Initial 12 Weeks of the Treatment Period in Participants Who Receive REGN1908-1909 Versus Placebo

The TOSS ranges from 0 to 6 and is based on 2 eye symptoms: itching/redness/gritty feeling and tearing/watering. Each of the 2 symptoms is graded on a Likert scale ranging from 0 (none) to 3 (severe).

Time frame: Weeks 0 to 12

Change From Baseline to Week 60 in Asthma Control Questionnaire 5 Question Version (ACQ-5) in Participant 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.

Time frame: Baseline to week 60

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)

Time frame: Weeks 48 to 60

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

Overview

Conditions

Interventions

Eligibility

Locations (92)

Outcomes

Primary Outcomes

Secondary Outcomes