Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of SAR440340 (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety and Tolerability of SAR440340, in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Primary Objective:

To investigate effects of SAR440340 (anti-interleukin-33 [IL-33] monoclonal antibody [mAb]) compared with placebo, on the annualized rate of moderate-to-severe acute exacerbations of COPD (AECOPD) over up to 52 weeks of treatment.

• Moderate exacerbations were recorded by the Investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics.
• Severe exacerbations were recorded by the Investigator and defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death.

Secondary Objectives:

To investigate effects of SAR440340 compared with placebo, on improving respiratory function, as assessed by pre-bronchodilator forced exploratory volume in 1 second (FEV1).

To evaluate effects of SAR440340 compared with placebo, on post-bronchodilator FEV1.

To evaluate effects of SAR440340 compared with placebo, on duration from baseline to first moderate or severe AECOPD event.

To evaluate effects of SAR440340 compared with placebo, on safety and tolerability.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Placebo; Drug: Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Drug: Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Drug: Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care; Drug: Any short-acting β agonist as prescribed by treating physician as standard of care; Drug: SAR440340

Detailed Description

Study participation for each participant were up to a total of 46 weeks to 76 weeks including up to 10 days to 4 weeks of screening, 24-to-52 week treatment period on investigational medical product (IMP), and 20 weeks of post IMP treatment period.

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Investigational Site Number 0320001
  • Caba, Argentina, C1425BEN
    • Investigational Site Number 0320002
  • Caba, Argentina, C1425FVH
    • Investigational Site Number 0320004
  • Caba, Argentina, C1414AIF
    • Investigational Site Number 0320005
  • Quilmes, Argentina, B1878FNR
    • Investigational Site Number 0320006
  • Rosario, Argentina, 2000
    • Investigational Site Number 0320003
• Australia
  • Bedford Park, Australia, 5042
    • Investigational Site Number 0360005
  • Chermside, Australia, 4032
    • Investigational Site Number 0360002
  • Clayton, Australia, 3168
    • Investigational Site Number 0360004
  • Frankston, Australia, 3199
    • Investigational Site Number 0360003
  • Kent Town, Australia, 5067
    • Investigational Site Number 0360006
  • Murdoch, Australia, 6150
    • Investigational Site Number 0360001
• Canada
  • Burlington, Canada, L7N 3V2
    • Investigational Site Number 1240002
  • Hamilton, Canada, L8N 4A6
    • Investigational Site Number 1240009
  • Montreal, Canada, H2X 3E4
    • Investigational Site Number 1240003
  • Montreal, Canada, H4A 3J1
    • Investigational Site Number 1240001
  • Quebec, Canada, G1V 4G5
    • Investigational Site Number 1240005
  • Saint-Charles-Borromée, Canada, J6E 2B4
    • Investigational Site Number 1240006
  • Trois-Rivieres, Canada, G8T 7A1
    • Investigational Site Number 1240008
  • Vancouver, Canada, V6Z 1Y6
    • Investigational Site Number 1240007
  • Victoriaville, Canada, G6P 6P6
    • Investigational Site Number 1240004
• Chile
  • Quillota, Chile, 2260877
    • Investigational Site Number 1520002
  • Santiago, Chile, 7500692
    • Investigational Site Number 1520001
  • Santiago, Chile, 8330336
    • Investigational Site Number 1520007
  • Santiago, Chile, 8910131
    • Investigational Site Number 1520004
  • Talca, Chile
    • Investigational Site Number 1520005
  • Talcahuano, Chile
    • Investigational Site Number 1520003
• Germany
  • Berlin, Germany, 10787
    • Investigational Site Number 2760006
  • Großhansdorf, Germany, 22927
    • Investigational Site Number 2760001
  • Hamburg, Germany, 20354
    • Investigational Site Number 2760002
  • Koblenz, Germany, 56068
    • Investigational Site Number 2760007
  • München, Germany, 81377
    • Investigational Site Number 2760004
  • Rüdersdorf Bei Berlin, Germany, 15562
    • Investigational Site Number 2760005
• Poland
  • Bialystok, Poland, 15-010
    • Investigational Site Number 6160001
  • Bialystok, Poland, 15-044
    • Investigational Site Number 6160008
  • Bydgoszcz, Poland, 85-079
    • Investigational Site Number 6160005
  • Grudziadz, Poland, 86-300
    • Investigational Site Number 6160009
  • Krakow, Poland, 31-559
    • Investigational Site Number 6160007
  • Poznan, Poland, 60-693
    • Investigational Site Number 6160002
  • Poznan, Poland, 60-823
    • Investigational Site Number 6160006
  • Rzeszow, Poland, 35-205
    • Investigational Site Number 6160010
  • Znin, Poland, 88-400
    • Investigational Site Number 6160003
• Russian Federation
  • Moscow, Russian Federation, 109240
    • Investigational Site Number 6430003
  • Moscow, Russian Federation, 109544
    • Investigational Site Number 6430001
  • Moscow, Russian Federation, 115280
    • Investigational Site Number 6430005
  • Moscow, Russian Federation, 117546
    • Investigational Site Number 6430002
  • Saint-Petersburg, Russian Federation, 194291
    • Investigational Site Number 6430010
  • Saint-Petersburg, Russian Federation, 194354
    • Investigational Site Number 6430006
  • St-Petersburg, Russian Federation, 193231
    • Investigational Site Number 6430007
  • Stavropol, Russian Federation, 355030
    • Investigational Site Number 6430009
  • Ulyanovsk, Russian Federation, 432017
    • Investigational Site Number 6430004
• Turkey
  • Ankara, Turkey, 06100
    • Investigational Site Number 7920004
  • Istanbul, Turkey, 34098
    • Investigational Site Number 7920001
  • Izmir, Turkey, 35040
    • Investigational Site Number 7920006
  • Izmir, Turkey, 35110
    • Investigational Site Number 7920007
  • Kirikkale, Turkey, 71450
    • Investigational site number 7920008
  • Mersin, Turkey, 33070
    • Investigational Site Number 7920002
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Investigational Site Number 8040008
  • Ivano-Frankivsk, Ukraine, 76000
    • Investigational Site Number 8040012
  • Ivano-Frankivsk, Ukraine, 76018
    • Investigational Site Number 8040004
  • Kharkiv, Ukraine, 61039
    • Investigational Site Number 8040002
  • Kharkiv, Ukraine, 61166
    • Investigational Site Number 8040011
  • Kyiv, Ukraine, 02125
    • Investigational Site Number 8040001
  • Kyiv, Ukraine, 02091
    • Investigational Site Number 8040007
  • Odesa, Ukraine, 65025
    • Investigational Site Number 8040006
  • Ternopil, Ukraine, 46000
    • Investigational Site Number 8040003
  • Vinnytsya, Ukraine, 21001
    • Investigational Site Number 8040005
• United States
  • California
    • Los Angeles, California, United States, 90025
      • Investigational Site Number 8400002
    • Riverside, California, United States, 92506
      • Investigational Site Number 8400003
    • Rolling Hills Estates, California, United States, 90274
      • Investigational Site Number 8400006
    • Westminster, California, United States, 92683
      • Investigational Site Number 8400015
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Investigational Site Number 8400013
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Investigational Site Number 8400012
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Investigational Site Number 8400016
    • South Dartmouth, Massachusetts, United States, 02747
      • Investigational Site Number 8400020
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Investigational Site Number 8400011
  • New York
    • Jamaica, New York, United States, 11418-2619
      • Investigational Site Number 8400005
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Investigational Site Number 8400019
    • Raleigh, North Carolina, United States, 27607
      • Investigational Site Number 8400004
  • Oregon
    • Medford, Oregon, United States, 97504
      • Investigational Site Number 8400001
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Investigational Site Number 8400009
  • Texas
    • Plano, Texas, United States, 75093
      • Investigational Site Number 8400007
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Investigational Site Number 8400008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Participants with a diagnosis of chronic obstructive pulmonary disease (COPD) for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition).
• Participants with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] less than [<] 70 percent (%) and post-bronchodilator FEV1% predicted <80%, but greater than equal to [>=] 30%).
• Participants with COPD assessment test (CAT) score >=10 at Screening.
• Participants with reported history of signs and symptoms of chronic bronchitis (chronic productive cough for 3 months in the year up to screening in a participant in whom other causes of chronic cough [e.g., gastroesophageal reflux, chronic rhinosinusitis, bronchiectasis] had been excluded).
• Participants with a documented history (e.g., medical record verification) of >=2 moderate exacerbations or >=1 severe exacerbation within the year prior to screening. A moderate exacerbation was defined as an acute exacerbation of COPD (AECOPD) requiring systemic corticosteroids (oral, intravenous, or intramuscular) and/or treatment with antibiotics (however, use of antibiotics alone does not qualify as a "moderate exacerbation" unless documentation was available that use of antibiotics was necessary for treatment of worsening symptoms of COPD). A severe exacerbation was defined as an AECOPD that required a hospitalization.
• Participants with standard of care background therapy, for 3 months and at a stable dose for at least 1 month, including either:
• Double therapy: Long acting beta agonist (LABA) + Long acting muscarinic agonist (LAMA) or inhaled corticosteroid (ICS) + LABA or ICS + LAMA.

or

• Triple therapy: LABA + LAMA + ICS.
• Current or former smokers with a smoking history of >=10 packs/year.

Exclusion criteria:

• Concomitant severe diseases or diseases for which the use of ICS (e.g., active pulmonary tuberculosis, etc.) or LABA were contraindicated (e.g., diagnosis of a history of significant cardiovascular diseases, insulin-dependent diabetes mellitus, hyperthyroidism, thyrotoxicosis, pheochromocytoma, hypokalemia).
• Use of injectable glucocorticosteroids or oral systemic glucocorticosteroids within previous 1 month or more than 4 courses of intravenous glucocorticosteroids within the previous 6 months.
• Participants with bronchial thermoplasty procedure (up to 3 years prior to Visit 1).
• A current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines.
• Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic granulomatosis with polyangiitis, significant sleep apnea on Bilevel Positive Airway Pressure, etc.) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• Diagnosis of α-1 anti-trypsin deficiency.
• Advanced COPD with need for chronic (greater than [>] 15 hours/day) oxygen support.
• Participant with a moderate or severe acute exacerbation of COPD event within previous 4 weeks.
• A participant who has experienced an upper or lower respiratory tract infection within previous 4 weeks.
• Prior history of or planned pneumonectomy or lung volume reduction surgery.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to SAR440340 administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W). Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, End of Treatment (EOT) visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	Drug: Placebo; Pharmaceutical form: Solution for injection; Route of administration: SC; Drug: Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler Route of administration: Inhaled; Drug: Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled; Drug: Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled; Drug: Any short-acting β agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: inhaled
Experimental: SAR440340; Participants received SAR440340 300 milligrams (mg) administered as 2 SC injections Q2W. Participants were treated for a minimum of 24 weeks and up to a maximum of 52 weeks (last dose administered at Week 50, EOT visit occurred 2 weeks after last administration of IMP i.e., at Week 52).	Drug: Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler Route of administration: Inhaled; Drug: Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled; Drug: Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled; Drug: Any short-acting β agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: inhaled; Drug: SAR440340; Pharmaceutical form: Solution for injection; Route of administration: SC; Other Names: REGN3500; Itepekimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Rate of Moderate to Severe Acute Exacerbation Events in Chronic Obstructive Pulmonary Disease (AECOPD) Participants	Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations events were defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.	From Baseline up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) From Baseline to Week 16 Through Week 24	FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry was performed after a wash out period of bronchodilators according to their action duration. A mixed-effect model with repeated measures (MMRM) was first used to model the change from baseline at each post randomization timepoint up to Week 24, then the predicted values of Week 16 to Week 24 were averaged to provide an overall assessment of change from baseline in FEV1.	From Baseline to Week 16 through Week 24
Change From Baseline in Post-bronchodilator Forced Expiratory Volume (FEV1) in 1 Second at Week 24	FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Post-bronchodilator FEV1 referred to the spirometry performed within 30 minutes after administration of bronchodilator (4 puffs of salbutamol/albuterol [100 micrograms {mcg}] or ipratropium bromide [20 mcg]).	Baseline, Week 24
Time to First Moderate or Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)	The time to first moderate or severe exacerbation was defined as onset date of first moderate or severe AECOPD minus randomization date + 1. The median time to first severe exacerbation was derived from Kaplan-Meier estimates. Moderate exacerbations events were recorded by the investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics. Severe exacerbations events were defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death.	From Baseline up to 52 weeks

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Rabe KF, Celli BR, Wechsler ME, Abdulai RM, Luo X, Boomsma MM, Staudinger H, Horowitz JE, Baras A, Ferreira MA, Ruddy MK, Nivens MC, Amin N, Weinreich DM, Yancopoulos GD, Goulaouic H. Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. Lancet Respir Med. 2021 Nov;9(11):1288-1298. doi: 10.1016/S2213-2600(21)00167-3. Epub 2021 Jul 21.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Actual): October 3, 2019
• Study Completion (Actual): February 21, 2020

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: October 28, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agonists; Cholinergic Agents; Muscarinic Agonists
• Other Study ID Numbers: ACT15104; 2017-003290-34 (EudraCT Number); U1111-1194-2134 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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