Clinical trial NCT02999711: Study of Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of REGN3500 in Adults With Moderate Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Moderate Asthma
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2016-12-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment emergent adverse events (TEAEs) after repeat subcutaneous administration
timeFrame: Up to 36 weeks
measure: Severity of TEAEs after repeat subcutaneous administration
timeFrame: Up to 36 weeks
Secondary outcomes:
measure: The concentration-time profile of REGN3500 after repeat subcutaneous administration
timeFrame: Up to 36 weeks
measure: Immunogenicity of REGN3500 assessed by measurement of anti-drug antibodies
timeFrame: Up to 36 weeks
measure: Percent change in total from baseline forced expiratory volume (FEV) at day 29
timeFrame: Baseline to week 4
measure: 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
timeFrame: From -14 days screening to week 4
measure: Absolute change from baseline fractional exhaled nitric oxide (FeNO) at day 29
timeFrame: Baseline to week 4
measure: Percent change from baseline FeNO at day 29
timeFrame: Baseline to week 4
measure: Change from baseline in biomarkers at day 29
timeFrame: Baseline to week 4
measure: Percent change from baseline in biomarkers at day 29
timeFrame: Baseline to week 4
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Regeneron Research Site
state: Northern Ireland
city: London
country: United Kingdom
facility: Regeneron Research Site
city: Manchester
country: United Kingdom
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.