Study of Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of REGN3500 in Adults With Moderate Asthma

A Randomised, Double-blind, Placebo-controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Effects of Subcutaneously Administered REGN3500 in Adult Patients With Moderate Asthma

Purpose of this study is to assess the safety and tolerability of multiple ascending subcutaneous doses of REGN3500 to moderate asthmatics.

Study Overview

• Status: Completed
• Conditions: Asthma; Moderate Asthma
• Intervention / Treatment: Drug: Placebo; Drug: REGN3500

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Regeneron Research Site
  • Manchester, United Kingdom
    • Regeneron Research Site
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Body mass index (BMI) of 18 to 32 kg/m2
• A diagnosis of moderate asthma (according to GINA 2015) for a period of at least 2 years prior to screening.
• Patient must use a stable medium daily dose level of inhaled corticosteroids (ICS) as defined by GINA guidelines, ie, total daily dose of ICS >400 μg and ≤800 μg/day of budesonide or equivalent for at least 1 month prior to screening and during the study
• A pre-bronchodilator forced expiratory volume in the first sec (FEV1) ≥60% and ≤90% of the predicted normal values at screening and pre-dose at screening
• A documented positive response to the reversibility test at the screening, defined as improvement in FEV1 ≥12% and ≥200 mL over baseline after 400 μg salbutamol Pmdi
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent.

Key Exclusion Criteria:

• Clinically significant abnormal CBC, clinical chemistry, and urine analysis at screening.
• Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, prior to screening.
• History of life-threatening asthma
• Occurrence of asthma exacerbations or respiratory tract infections within 4 weeks prior to screening.
• Diagnosis of any other airway/pulmonary disease such as Chronic Obstructive Pulmonary Disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (GOLD 2016); or other lung diseases (eg, emphysema, idiopathic pulmonary fibrosis, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency or restrictive lung disease).
• Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 1 month prior to screening.
• Use of oral antibiotics/anti-infectives within 2 weeks prior to screening.
• Known sensitivity to doxycycline or tetracyclines, or to any of the components of the investigational product formulation.
• Recent (within the previous 2 months) bacterial, protozoal, viral, or parasite infection.
• History of tuberculosis or systemic fungal diseases
• Patients treated with a monoclonal antibody based therapy (such as an anti-IgE, anti-IL-5), a biologic therapy or immunotherapy (subcutaneous immunotherapy [SCIT], sublingual immunotherapy [SLIT], or oral immunotherapy [OIT]) in the previous 12 weeks prior to screening and during the study

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; REGN3500 low dose or placebo	Drug: Placebo; Matching placebo; Drug: REGN3500; REGN3500 dose
Experimental: Cohort 2; REGN3500 medium dose or placebo	Drug: Placebo; Matching placebo; Drug: REGN3500; REGN3500 dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment emergent adverse events (TEAEs) after repeat subcutaneous administration	Up to 36 weeks
Severity of TEAEs after repeat subcutaneous administration	Up to 36 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The concentration-time profile of REGN3500 after repeat subcutaneous administration	Up to 36 weeks
Immunogenicity of REGN3500 assessed by measurement of anti-drug antibodies	Up to 36 weeks
Percent change in total from baseline forced expiratory volume (FEV) at day 29	Baseline to week 4
Percent change of the average of the prior 7 days of FEV1 at day 29 compared to average daily FEV1 during the last 14 days of screening	From -14 days screening to week 4
Absolute change from baseline fractional exhaled nitric oxide (FeNO) at day 29	Baseline to week 4
Percent change from baseline FeNO at day 29	Baseline to week 4
Change from baseline in biomarkers at day 29	Baseline to week 4
Percent change from baseline in biomarkers at day 29	Baseline to week 4

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Kosloski MP, Kalliolias GD, Xu CR, Harel S, Lai CH, Zheng W, Davis JD, Kamal MA. Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. Clin Transl Sci. 2022 Feb;15(2):384-395. doi: 10.1111/cts.13157. Epub 2021 Sep 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2017
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: December 10, 2018
• Last Verified: December 1, 2018

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
• Other Study ID Numbers: R3500-AS-1619; 2016-002979-95 (EudraCT Number)

Drug and device information, study documents

• 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