Study of REGN3500 and Dupilumab in Patients With Asthma

A Randomized, Placebo-controlled, Parallel Panel Study to Assess the Effects of REGN3500, Dupilumab, and Combination of REGN3500 Plus Dupilumab on Markers of Inflammation After Bronchial Allergen Challenge in Patients With Allergic Asthma

To assess the effects of REGN3500, dupilumab, and REGN3500 plus dupilumab, compared with placebo, on changes in inflammatory gene expression signatures in sputum induced after a bronchial allergen challenge (BAC) in adults with mild allergic asthma, at week 4 after treatment initiation compared with those at screening.

Study Overview

• Status: Completed
• Conditions: Asthma, Allergic
• Intervention / Treatment: Drug: Placebo; Drug: REGN3500; Drug: Dupilumab; Drug: Fluticasone propionate

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 6AD
    • Celerion
  • London, United Kingdom, W1G 8HU
    • Respiratory Clinical Trials Ltd
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicine Research
  • Manchester, United Kingdom, M23 9QZ
    • The Medicines Evaluation Unit
• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

KEY Inclusion Criteria:

1. Male or female aged between 18 and 60 years
2. Has a Body Mass Index {BMI) of 17 to 33 kg/m2 at pre-study screening
3. Has a history of mild allergic asthma for at least 6 months
4. Is a non-smoker or ex-smoker for at least 12 months

KEY Exclusion Criteria:

1. Has a history of life-threatening asthma
2. Has been hospitalized or has attended the emergency room for asthma in the 12 months prior to screening
3. Has a history of severe allergies or history of an anaphylactic reaction
4. Has a history of drug or alcohol abuse within a year prior to the screening visit

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN3500; REGN3500: masked and randomized dosing regimen per protocol (part 1 only)	Drug: REGN3500; Intravenous (IV) use
Experimental: Dupilumab; Dupilumab: masked and randomized dosing regimen per protocol (part 1 only)	Drug: Dupilumab; Subcutaneous (SC) use; Other Names: Dupixent
Experimental: REGN3500 plus dupilumab; REGN3500 plus dupilumab: masked and randomized dosing regimen per protocol (part 1 only)	Drug: REGN3500; Intravenous (IV) use; Drug: Dupilumab; Subcutaneous (SC) use; Other Names: Dupixent
Experimental: Placebo; Placebo: masked and randomized dosing regimen per protocol (part 1 only)	Drug: Placebo; Matching placebo
Active Comparator: Fluticasone propionate; Fluticasone propionate: open label dosing regimen per protocol (part 2 only)	Drug: Fluticasone propionate; Inhalation use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in bronchial allergen challenge (BAC)-induced changes in sputum inflammatory markers in individuals treated with REGN3500, dupilumab and the combination of REGN3500 plus dupilumab or placebo	Screening (pre-treatment) to week 4 after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events (TEAEs)		Baseline to week 42
Severity of TEAEs		Baseline to week 42
Serum concentration-time profile of REGN3500	Assessed by maximum plasma concentration [Cmax]	Baseline to week 42
Serum concentration-time profile of REGN3500: Tmax (time at Cmax)		Baseline to week 42
Serum concentration-time profile of REGN3500: AUClast (area under the curve to the last measurable concentration)		Baseline to week 42
Immunogenicity of REGN3500 and dupilumab	Assessed by measurement of anti-drug antibodies (ADAs)	Baseline to week 42
Serum concentration of total IL-33 after single IV dose		Up to Week 42
Difference in the BAC-induced changes in sputum inflammatory mRNA signature in individual patients treated with fluticasone		Screening (pre-treatment) to day 4 after treatment initiation

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Actual): March 20, 2019
• Study Completion (Actual): December 9, 2019

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (Actual): April 13, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 16, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: R3500-AS-1633; 2016-003165-26 (EudraCT Number); SAR440340 (Other Identifier: Sanofi)

Drug and device information, study documents

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