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

• ClinicalTrials.gov Identifier: NCT03838731
• Recruitment Status: Completed
• First Posted: February 12, 2019
• Results First Posted: July 1, 2021
• Last Update Posted: July 1, 2021
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cat Allergy; Mild Asthma	Drug: REGN1908-1909; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 12, 2019
• Actual Primary Completion Date: December 21, 2019
• Actual Study Completion Date: April 6, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: REGN1908-1909	Drug: REGN1908-1909; Single subcutaneous (SC) dose of REGN1908 and REGN1909
Placebo Comparator: Placebo	Drug: Placebo; Single subcutaneous (SC) dose of matching placebo

Outcome Measures

Primary Outcome Measures :

1. Time to Early Asthmatic Response (EAR) Upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8 [ Time Frame: 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.

Secondary Outcome Measures :

1. Time to EAR Upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85 [ Time Frame: 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
2. 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 [ Time Frame: 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.
3. 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 [ Time Frame: 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.
4. 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 [ Time Frame: 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.
5. 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 [ Time Frame: 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.
6. Mean Change From Baseline in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 [ Time Frame: 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.
7. Percent Change in Cat Allergen Quantity as Experienced by Participants During Exposure on Days 8, 29, 57, and 85 [ Time Frame: 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.
8. Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study [ Time Frame: Baseline to 16 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

Regeneron Research Site

Strasbourg, France, 67000

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:

Study Protocol  [PDF] May 20, 2019

Statistical Analysis Plan  [PDF] January 30, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Blay FJ, Gherasim A, Domis N, Meier P, Shawki F, Wang CQ, Orengo JM, DeVeaux M, Ramesh D, Jalbert JJ, Kamal MA, Abdallah H, Dingman R, Perlee L, Weinreich DM, Herman G, Yancopoulos GD, O'Brien MP. REGN1908/1909 prevented cat allergen-induced early asthmatic responses in an environmental exposure unit. J Allergy Clin Immunol. 2022 Dec;150(6):1437-1446. doi: 10.1016/j.jaci.2022.06.025. Epub 2022 Aug 4.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03838731
• Other Study ID Numbers: R1908-1909-ALG-1703; 2018-002477-22 ( EudraCT Number )
• First Posted: February 12, 2019
• Results First Posted: July 1, 2021
• Last Update Posted: July 1, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification
• Access Criteria: Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification
• URL: https://vivli.org/

• 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

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases