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)

Phase 2

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Placebo; Drug: SAR440340; 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

• Registration Number: NCT03546907
• Lead Sponsor: Sanofi

Brief 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.

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 Timeline

• Study First Submitted: 2018-05-17
• Study First Submitted QC: 2018-06-04
• Study First Posted: 2018-06-06
• Study Start: 2018-07-16
• Primary Completion: 2019-10-03
• Study Completion: 2020-02-21
• Disposition First Submitted: 2020-09-28
• Results First Submitted: 2022-09-23
• Status Verified: 2022-10
• Results First Submitted QC: 2022-10-28
• Disposition First Submitted QC: 2022-10-28
• Last Update Submitted: 2022-10-28
• Results First Posted: 2022-11-22
• Disposition First Posted: 2022-11-22
• Last Update Posted: 2022-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 343

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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).
Placebo	Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care	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).
Placebo	Any Inhaled Corticosteroids as prescribed by treating physician as standard of care	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).
Placebo	Any Long Acting Beta Agonist as prescribed by treating physician as standard of care	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).
Placebo	Any short-acting β agonist as prescribed by treating physician as standard of care	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).
SAR440340	Any Inhaled Corticosteroids as prescribed by treating physician as standard of care	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).
SAR440340	Any Long Acting Beta Agonist as prescribed by treating physician as standard of care	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).
SAR440340	Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care	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).
SAR440340	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).
SAR440340	Any short-acting β agonist as prescribed by treating physician as standard of care	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).

Primary Outcome Measures

Name	Time	Method
Annualized Rate of Moderate to Severe Acute Exacerbation Events in Chronic Obstructive Pulmonary Disease (AECOPD) Participants	From Baseline up to Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Average Change in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) From Baseline to Week 16 Through Week 24	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.
Change From Baseline in Post-bronchodilator Forced Expiratory Volume (FEV1) in 1 Second at Week 24	Baseline, 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 \[20 mcg\]).
Time to First Moderate or Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)	From Baseline up to 52 weeks	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.

Trial Locations

Locations (83)

Investigational Site Number 0320005; 🇦🇷 Caba, Argentina

Investigational Site Number 6160002; 🇵🇱 Poznan, Poland

Investigational Site Number 0320002; 🇦🇷 Caba, Argentina

Investigational Site Number 0320004; 🇦🇷 Caba, Argentina

Investigational Site Number 1520007; 🇨🇱 Santiago, Chile

Investigational Site Number 6430006; 🇷🇺 Saint-Petersburg, Russian Federation

Investigational Site Number 6430003; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 6160008; 🇵🇱 Bialystok, Poland

Investigational Site Number 6430007; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 6430009; 🇷🇺 Stavropol, Russian Federation

Investigational Site Number 8040008; 🇺🇦 Chernivtsi, Ukraine

Investigational Site Number 6160010; 🇵🇱 Rzeszow, Poland

Investigational Site Number 6430010; 🇷🇺 Saint-Petersburg, Russian Federation

Investigational Site Number 6430001; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 8040004; 🇺🇦 Ivano-Frankivsk, Ukraine

Investigational Site Number 8400004; 🇺🇸 Raleigh, North Carolina, United States

Investigational Site Number 8400012; 🇺🇸 Columbia, Maryland, United States

Investigational Site Number 7920001; 🇹🇷 Istanbul, Turkey

Investigational Site Number 8040012; 🇺🇦 Ivano-Frankivsk, Ukraine

Investigational Site Number 8400016; 🇺🇸 North Dartmouth, Massachusetts, United States

Investigational Site Number 8400015; 🇺🇸 Westminster, California, United States

Investigational Site Number 8400001; 🇺🇸 Medford, Oregon, United States

Investigational Site Number 8400013; 🇺🇸 Jacksonville, Florida, United States

Investigational Site Number 8400007; 🇺🇸 Plano, Texas, United States

Investigational Site Number 0360005; 🇦🇺 Bedford Park, Australia

Investigational Site Number 8400009; 🇺🇸 Philadelphia, Pennsylvania, United States

Investigational Site Number 0320001; 🇦🇷 Buenos Aires, Argentina

Investigational Site Number 0360001; 🇦🇺 Murdoch, Australia

Investigational Site Number 0360006; 🇦🇺 Kent Town, Australia

Investigational Site Number 2760004; 🇩🇪 München, Germany

Investigational Site Number 1240005; 🇨🇦 Quebec, Canada

Investigational Site Number 1240009; 🇨🇦 Hamilton, Canada

Investigational Site Number 0360002; 🇦🇺 Chermside, Australia

Investigational Site Number 8400008; 🇺🇸 Greenfield, Wisconsin, United States

Investigational Site Number 1520001; 🇨🇱 Santiago, Chile

Investigational Site Number 2760001; 🇩🇪 Großhansdorf, Germany

Investigational Site Number 7920002; 🇹🇷 Mersin, Turkey

Investigational Site Number 1240003; 🇨🇦 Montreal, Canada

Investigational Site Number 1240008; 🇨🇦 Trois-Rivieres, Canada

Investigational Site Number 1520002; 🇨🇱 Quillota, Chile

Investigational Site Number 1520004; 🇨🇱 Santiago, Chile

Investigational Site Number 1520003; 🇨🇱 Talcahuano, Chile

Investigational Site Number 1240001; 🇨🇦 Montreal, Canada

Investigational Site Number 1240006; 🇨🇦 Saint-Charles-Borromée, Canada

Investigational Site Number 1240004; 🇨🇦 Victoriaville, Canada

Investigational Site Number 1240007; 🇨🇦 Vancouver, Canada

Investigational Site Number 1520005; 🇨🇱 Talca, Chile

Investigational Site Number 6160005; 🇵🇱 Bydgoszcz, Poland

Investigational Site Number 6160006; 🇵🇱 Poznan, Poland

Investigational Site Number 6160003; 🇵🇱 Znin, Poland

Investigational Site Number 6160001; 🇵🇱 Bialystok, Poland

Investigational Site Number 7920007; 🇹🇷 Izmir, Turkey

Investigational Site Number 6160009; 🇵🇱 Grudziadz, Poland

Investigational Site Number 6430005; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 6430004; 🇷🇺 Ulyanovsk, Russian Federation

Investigational Site Number 7920004; 🇹🇷 Ankara, Turkey

Investigational Site Number 8040005; 🇺🇦 Vinnytsya, Ukraine

Investigational Site Number 2760006; 🇩🇪 Berlin, Germany

Investigational Site Number 2760002; 🇩🇪 Hamburg, Germany

Investigational Site Number 8400005; 🇺🇸 Jamaica, New York, United States

Investigational Site Number 0360004; 🇦🇺 Clayton, Australia

Investigational Site Number 8400020; 🇺🇸 South Dartmouth, Massachusetts, United States

Investigational Site Number 2760007; 🇩🇪 Koblenz, Germany

Investigational Site Number 0360003; 🇦🇺 Frankston, Australia

Investigational Site Number 8400003; 🇺🇸 Riverside, California, United States

Investigational Site Number 8400006; 🇺🇸 Rolling Hills Estates, California, United States

Investigational Site Number 0320003; 🇦🇷 Rosario, Argentina

Investigational Site Number 0320006; 🇦🇷 Quilmes, Argentina

Investigational Site Number 1240002; 🇨🇦 Burlington, Canada

Investigational Site Number 2760005; 🇩🇪 Rüdersdorf Bei Berlin, Germany

Investigational Site Number 6430002; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 6160007; 🇵🇱 Krakow, Poland

Investigational Site Number 7920008; 🇹🇷 Kirikkale, Turkey

Investigational Site Number 7920006; 🇹🇷 Izmir, Turkey

Investigational Site Number 8040002; 🇺🇦 Kharkiv, Ukraine

Investigational Site Number 8040006; 🇺🇦 Odesa, Ukraine

Investigational Site Number 8040011; 🇺🇦 Kharkiv, Ukraine

Investigational Site Number 8040001; 🇺🇦 Kyiv, Ukraine

Investigational Site Number 8040003; 🇺🇦 Ternopil, Ukraine

Investigational Site Number 8040007; 🇺🇦 Kyiv, Ukraine

Investigational Site Number 8400002; 🇺🇸 Los Angeles, California, United States

Investigational Site Number 8400011; 🇺🇸 Minneapolis, Minnesota, United States

Investigational Site Number 8400019; 🇺🇸 Chapel Hill, North Carolina, United States