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)

NCT ID: NCT03546907

Last Updated: 2022-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 343 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-16
• Study Completion Date: 2020-02-21

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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: SC

Any Inhaled Corticosteroids as prescribed by treating physician as standard of care

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled

Any short-acting β agonist as prescribed by treating physician as standard of care

Intervention Type: DRUG

Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: inhaled

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).

Group Type: EXPERIMENTAL

SAR440340

Intervention Type: DRUG

Pharmaceutical form: Solution for injection; Route of administration: SC

Any Inhaled Corticosteroids as prescribed by treating physician as standard of care

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: Inhaled

Any short-acting β agonist as prescribed by treating physician as standard of care

Intervention Type: DRUG

Pharmaceutical form: Aerosol or Dry Powder inhaler; Route of administration: inhaled

Interventions

SAR440340

Pharmaceutical form: Solution for injection; Route of administration: SC

Intervention Type: DRUG

Placebo

Pharmaceutical form: Solution for injection; Route of administration: SC

Intervention Type: DRUG

Any Inhaled Corticosteroids as prescribed by treating physician as standard of care

Pharmaceutical form: Aerosol or Dry Powder inhaler Route of administration: Inhaled

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Itepekimab; REGN3500

Eligibility Criteria

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400002

Los Angeles, California, United States

Investigational Site Number 8400003

Riverside, California, United States

Investigational Site Number 8400006

Rolling Hills Estates, California, United States

Investigational Site Number 8400015

Westminster, California, United States

Investigational Site Number 8400013

Jacksonville, Florida, United States

Investigational Site Number 8400012

Columbia, Maryland, United States

Investigational Site Number 8400016

North Dartmouth, Massachusetts, United States

Investigational Site Number 8400020

South Dartmouth, Massachusetts, United States

Investigational Site Number 8400011

Minneapolis, Minnesota, United States

Investigational Site Number 8400005

Jamaica, New York, United States

Investigational Site Number 8400019

Chapel Hill, North Carolina, United States

Investigational Site Number 8400004

Raleigh, North Carolina, United States

Investigational Site Number 8400001

Medford, Oregon, United States

Investigational Site Number 8400009

Philadelphia, Pennsylvania, United States

Investigational Site Number 8400007

Plano, Texas, United States

Investigational Site Number 8400008

Greenfield, Wisconsin, United States

Investigational Site Number 0320001

Buenos Aires, , Argentina

Investigational Site Number 0320005

Caba, , Argentina

Investigational Site Number 0320002

Caba, , Argentina

Investigational Site Number 0320004

Caba, , Argentina

Investigational Site Number 0320006

Quilmes, , Argentina

Investigational Site Number 0320003

Rosario, , Argentina

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, , Australia

Investigational Site Number 1240002

Burlington, , Canada

Investigational Site Number 1240009

Hamilton, , Canada

Investigational Site Number 1240003

Montreal, , Canada

Investigational Site Number 1240001

Montreal, , Canada

Investigational Site Number 1240005

Québec, , Canada

Investigational Site Number 1240006

Saint-Charles-Borromée, , Canada

Investigational Site Number 1240008

Trois-Rivières, , Canada

Investigational Site Number 1240007

Vancouver, , Canada

Investigational Site Number 1240004

Victoriaville, , Canada

Investigational Site Number 1520002

Quillota, , Chile

Investigational Site Number 1520001

Santiago, , Chile

Investigational Site Number 1520007

Santiago, , Chile

Investigational Site Number 1520004

Santiago, , Chile

Investigational Site Number 1520005

Talca, , Chile

Investigational Site Number 1520003

Talcahuano, , Chile

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, , Germany

Investigational Site Number 6160001

Bialystok, , Poland

Investigational Site Number 6160008

Bialystok, , Poland

Investigational Site Number 6160005

Bydgoszcz, , Poland

Investigational Site Number 6160009

Grudziądz, , Poland

Investigational Site Number 6160007

Krakow, , Poland

Investigational Site Number 6160002

Poznan, , Poland

Investigational Site Number 6160006

Poznan, , Poland

Investigational Site Number 6160010

Rzeszów, , Poland

Investigational Site Number 6160003

Żnin, , Poland

Investigational Site Number 6430003

Moscow, , Russia

Investigational Site Number 6430001

Moscow, , Russia

Investigational Site Number 6430005

Moscow, , Russia

Investigational Site Number 6430002

Moscow, , Russia

Investigational Site Number 6430007

Saint Petersburg, , Russia

Investigational Site Number 6430010

Saint Petersburg, , Russia

Investigational Site Number 6430006

Saint Petersburg, , Russia

Investigational Site Number 6430009

Stavropol, , Russia

Investigational Site Number 6430004

Ulyanovsk, , Russia

Investigational Site Number 7920004

Ankara, , Turkey (Türkiye)

Investigational Site Number 7920001

Istanbul, , Turkey (Türkiye)

Investigational Site Number 7920006

Izmir, , Turkey (Türkiye)

Investigational Site Number 7920007

Izmir, , Turkey (Türkiye)

Investigational Site Number 7920008

Kırıkkale, , Turkey (Türkiye)

Investigational Site Number 7920002

Mersin, , Turkey (Türkiye)

Investigational Site Number 8040008

Chernivtsi, , Ukraine

Investigational Site Number 8040012

Ivano-Frankivsk, , Ukraine

Investigational Site Number 8040004

Ivano-Frankivsk, , Ukraine

Investigational Site Number 8040002

Kharkiv, , Ukraine

Investigational Site Number 8040011

Kharkiv, , Ukraine

Investigational Site Number 8040007

Kyiv, , Ukraine

Investigational Site Number 8040001

Kyiv, , Ukraine

Investigational Site Number 8040006

Odesa, , Ukraine

Investigational Site Number 8040003

Ternopil, , Ukraine

Investigational Site Number 8040005

Vinnytsia, , Ukraine

Countries

United States; Argentina; Australia; Canada; Chile; Germany; Poland; Russia; Turkey (Türkiye); Ukraine

References

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.

Reference Type: DERIVED

PMID: 34302758 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-003290-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1194-2134

Identifier Type: OTHER

Identifier Source: secondary_id

ACT15104

Identifier Type: -

Identifier Source: org_study_id