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)

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03546907
• Other study ID #: ACT15104
• Secondary ID: 2017-003290-34U1
• Status: Completed
• Phase: Phase 2
• Start date: July 16, 2018
• Est. completion date: February 21, 2020

Study information

• Verified date: October 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 343
• Est. completion date: February 21, 2020
• Est. primary completion date: October 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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 a-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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• SAR440340
Pharmaceutical form: Solution for injection; Route of administration: SC
• Placebo
Pharmaceutical form: Solution for injection; Route of administration: SC
• Any Inhaled Corticosteroids as prescribed by treating physician as standard of care
Pharmaceutical form: Aerosol or Dry Powder inhaler Route of administration: Inhaled
• 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
• 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
• Any short-acting ß agonist as prescribed by treating physician as standard of care
Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: inhaled

Locations

Country	Name	City	State
Argentina	Investigational Site Number 0320001	Buenos Aires
Argentina	Investigational Site Number 0320002	Caba
Argentina	Investigational Site Number 0320004	Caba
Argentina	Investigational Site Number 0320005	Caba
Argentina	Investigational Site Number 0320006	Quilmes
Argentina	Investigational Site Number 0320003	Rosario
Australia	Investigational Site Number 0360005	Bedford Park
Australia	Investigational Site Number 0360002	Chermside
Australia	Investigational Site Number 0360004	Clayton
Australia	Investigational Site Number 0360003	Frankston
Australia	Investigational Site Number 0360006	Kent Town
Australia	Investigational Site Number 0360001	Murdoch
Canada	Investigational Site Number 1240002	Burlington
Canada	Investigational Site Number 1240009	Hamilton
Canada	Investigational Site Number 1240001	Montreal
Canada	Investigational Site Number 1240003	Montreal
Canada	Investigational Site Number 1240005	Quebec
Canada	Investigational Site Number 1240006	Saint-Charles-Borromée
Canada	Investigational Site Number 1240008	Trois-Rivieres
Canada	Investigational Site Number 1240007	Vancouver
Canada	Investigational Site Number 1240004	Victoriaville
Chile	Investigational Site Number 1520002	Quillota
Chile	Investigational Site Number 1520001	Santiago
Chile	Investigational Site Number 1520004	Santiago
Chile	Investigational Site Number 1520007	Santiago
Chile	Investigational Site Number 1520005	Talca
Chile	Investigational Site Number 1520003	Talcahuano
Germany	Investigational Site Number 2760006	Berlin
Germany	Investigational Site Number 2760001	Großhansdorf
Germany	Investigational Site Number 2760002	Hamburg
Germany	Investigational Site Number 2760007	Koblenz
Germany	Investigational Site Number 2760004	München
Germany	Investigational Site Number 2760005	Rüdersdorf Bei Berlin
Poland	Investigational Site Number 6160001	Bialystok
Poland	Investigational Site Number 6160008	Bialystok
Poland	Investigational Site Number 6160005	Bydgoszcz
Poland	Investigational Site Number 6160009	Grudziadz
Poland	Investigational Site Number 6160007	Krakow
Poland	Investigational Site Number 6160002	Poznan
Poland	Investigational Site Number 6160006	Poznan
Poland	Investigational Site Number 6160010	Rzeszow
Poland	Investigational Site Number 6160003	Znin
Russian Federation	Investigational Site Number 6430001	Moscow
Russian Federation	Investigational Site Number 6430002	Moscow
Russian Federation	Investigational Site Number 6430003	Moscow
Russian Federation	Investigational Site Number 6430005	Moscow
Russian Federation	Investigational Site Number 6430006	Saint-Petersburg
Russian Federation	Investigational Site Number 6430010	Saint-Petersburg
Russian Federation	Investigational Site Number 6430007	St-Petersburg
Russian Federation	Investigational Site Number 6430009	Stavropol
Russian Federation	Investigational Site Number 6430004	Ulyanovsk
Turkey	Investigational Site Number 7920004	Ankara
Turkey	Investigational Site Number 7920001	Istanbul
Turkey	Investigational Site Number 7920006	Izmir
Turkey	Investigational Site Number 7920007	Izmir
Turkey	Investigational Site Number 7920008	Kirikkale
Turkey	Investigational Site Number 7920002	Mersin
Ukraine	Investigational Site Number 8040008	Chernivtsi
Ukraine	Investigational Site Number 8040004	Ivano-Frankivsk
Ukraine	Investigational Site Number 8040012	Ivano-Frankivsk
Ukraine	Investigational Site Number 8040002	Kharkiv
Ukraine	Investigational Site Number 8040011	Kharkiv
Ukraine	Investigational Site Number 8040001	Kyiv
Ukraine	Investigational Site Number 8040007	Kyiv
Ukraine	Investigational Site Number 8040006	Odesa
Ukraine	Investigational Site Number 8040003	Ternopil
Ukraine	Investigational Site Number 8040005	Vinnytsya
United States	Investigational Site Number 8400019	Chapel Hill	North Carolina
United States	Investigational Site Number 8400012	Columbia	Maryland
United States	Investigational Site Number 8400008	Greenfield	Wisconsin
United States	Investigational Site Number 8400013	Jacksonville	Florida
United States	Investigational Site Number 8400005	Jamaica	New York
United States	Investigational Site Number 8400002	Los Angeles	California
United States	Investigational Site Number 8400001	Medford	Oregon
United States	Investigational Site Number 8400011	Minneapolis	Minnesota
United States	Investigational Site Number 8400016	North Dartmouth	Massachusetts
United States	Investigational Site Number 8400009	Philadelphia	Pennsylvania
United States	Investigational Site Number 8400007	Plano	Texas
United States	Investigational Site Number 8400004	Raleigh	North Carolina
United States	Investigational Site Number 8400003	Riverside	California
United States	Investigational Site Number 8400006	Rolling Hills Estates	California
United States	Investigational Site Number 8400020	South Dartmouth	Massachusetts
United States	Investigational Site Number 8400015	Westminster	California

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Germany,  Poland,  Russian Federation,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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