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)

NCT03546907 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: ACT151042017-003290-34U1111-1194-2134
• Study Type: interventional
• Target: 343
• Locations: 10 countries
• Sites: 83

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

• Change From Baseline in Post-bronchodilator Forced Expiratory Volume (FEV1) in 1 Second at Week 24

  Baseline, Week 24

• Time to First Moderate or Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)

  From Baseline up to 52 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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; 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

SAR440340

EXPERIMENTAL

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: 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

Interventions

SAR440340 DRUG

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

Also known as: Itepekimab, REGN3500

SAR440340

Placebo DRUG

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

Placebo

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

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

Placebo; SAR440340

Any Long Acting Beta Agonist as prescribed by treating physician as standard of care DRUG

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

Placebo; SAR440340

Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care DRUG

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

Placebo; SAR440340

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

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

Placebo; SAR440340

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (83)

Investigational Site Number 8400002

Los Angeles, California, 90025, United States

Location

Investigational Site Number 8400003

Riverside, California, 92506, United States

Location

Investigational Site Number 8400006

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 8400015

Westminster, California, 92683, United States

Location

Investigational Site Number 8400013

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 8400012

Columbia, Maryland, 21044, United States

Location

Investigational Site Number 8400016

North Dartmouth, Massachusetts, 02747, United States

Location

Investigational Site Number 8400020

South Dartmouth, Massachusetts, 02747, United States

Location

Investigational Site Number 8400011

Minneapolis, Minnesota, 55407, United States

Location

Investigational Site Number 8400005

Jamaica, New York, 11418-2619, United States

Location

Investigational Site Number 8400019

Chapel Hill, North Carolina, 27517, United States

Location

Investigational Site Number 8400004

Raleigh, North Carolina, 27607, United States

Location

Investigational Site Number 8400001

Medford, Oregon, 97504, United States

Location

Investigational Site Number 8400009

Philadelphia, Pennsylvania, 19140, United States

Location

Investigational Site Number 8400007

Plano, Texas, 75093, United States

Location

Investigational Site Number 8400008

Greenfield, Wisconsin, 53228, United States

Location

Investigational Site Number 0320001

Buenos Aires, C1121ABE, Argentina

Location

Investigational Site Number 0320005

Caba, C1414AIF, Argentina

Location

Investigational Site Number 0320002

Caba, C1425BEN, Argentina

Location

Investigational Site Number 0320004

Caba, C1425FVH, Argentina

Location

Investigational Site Number 0320006

Quilmes, B1878FNR, Argentina

Location

Investigational Site Number 0320003

Rosario, 2000, Argentina

Location

Investigational Site Number 0360005

Bedford Park, 5042, Australia

Location

Investigational Site Number 0360002

Chermside, 4032, Australia

Location

Investigational Site Number 0360004

Clayton, 3168, Australia

Location

Investigational Site Number 0360003

Frankston, 3199, Australia

Location

Investigational Site Number 0360006

Kent Town, 5067, Australia

Location

Investigational Site Number 0360001

Murdoch, 6150, Australia

Location

Investigational Site Number 1240002

Burlington, L7N 3V2, Canada

Location

Investigational Site Number 1240009

Hamilton, L8N 4A6, Canada

Location

Investigational Site Number 1240003

Montreal, H2X 3E4, Canada

Location

Investigational Site Number 1240001

Montreal, H4A 3J1, Canada

Location

Investigational Site Number 1240005

Québec, G1V 4G5, Canada

Location

Investigational Site Number 1240006

Saint-Charles-Borromée, J6E 2B4, Canada

Location

Investigational Site Number 1240008

Trois-Rivières, G8T 7A1, Canada

Location

Investigational Site Number 1240007

Vancouver, V6Z 1Y6, Canada

Location

Investigational Site Number 1240004

Victoriaville, G6P 6P6, Canada

Location

Investigational Site Number 1520002

Quillota, 2260877, Chile

Location

Investigational Site Number 1520001

Santiago, 7500692, Chile

Location

Investigational Site Number 1520007

Santiago, 8330336, Chile

Location

Investigational Site Number 1520004

Santiago, 8910131, Chile

Location

Investigational Site Number 1520005

Talca, Chile

Location

Investigational Site Number 1520003

Talcahuano, Chile

Location

Investigational Site Number 2760006

Berlin, 10787, Germany

Location

Investigational Site Number 2760001

Großhansdorf, 22927, Germany

Location

Investigational Site Number 2760002

Hamburg, 20354, Germany

Location

Investigational Site Number 2760007

Koblenz, 56068, Germany

Location

Investigational Site Number 2760004

München, 81377, Germany

Location

Investigational Site Number 2760005

Rüdersdorf Bei Berlin, 15562, Germany

Location

Investigational Site Number 6160001

Bialystok, 15-010, Poland

Location

Investigational Site Number 6160008

Bialystok, 15-044, Poland

Location

Investigational Site Number 6160005

Bydgoszcz, 85-079, Poland

Location

Investigational Site Number 6160009

Grudziądz, 86-300, Poland

Location

Investigational Site Number 6160007

Krakow, 31-559, Poland

Location

Investigational Site Number 6160002

Poznan, 60-693, Poland

Location

Investigational Site Number 6160006

Poznan, 60-823, Poland

Location

Investigational Site Number 6160010

Rzeszów, 35-205, Poland

Location

Investigational Site Number 6160003

Żnin, 88-400, Poland

Location

Investigational Site Number 6430003

Moscow, 109240, Russia

Location

Investigational Site Number 6430001

Moscow, 109544, Russia

Location

Investigational Site Number 6430005

Moscow, 115280, Russia

Location

Investigational Site Number 6430002

Moscow, 117546, Russia

Location

Investigational Site Number 6430007

Saint Petersburg, 193231, Russia

Location

Investigational Site Number 6430010

Saint Petersburg, 194291, Russia

Location

Investigational Site Number 6430006

Saint Petersburg, 194354, Russia

Location

Investigational Site Number 6430009

Stavropol, 355030, Russia

Location

Investigational Site Number 6430004

Ulyanovsk, 432017, Russia

Location

Investigational Site Number 7920004

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 7920001

Istanbul, 34098, Turkey (Türkiye)

Location

Investigational Site Number 7920006

Izmir, 35040, Turkey (Türkiye)

Location

Investigational Site Number 7920007

Izmir, 35110, Turkey (Türkiye)

Location

Investigational Site Number 7920008

Kırıkkale, 71450, Turkey (Türkiye)

Location

Investigational Site Number 7920002

Mersin, 33070, Turkey (Türkiye)

Location

Investigational Site Number 8040008

Chernivtsi, 58001, Ukraine

Location

Investigational Site Number 8040012

Ivano-Frankivsk, 76000, Ukraine

Location

Investigational Site Number 8040004

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number 8040002

Kharkiv, 61039, Ukraine

Location

Investigational Site Number 8040011

Kharkiv, 61166, Ukraine

Location

Investigational Site Number 8040007

Kyiv, 02091, Ukraine

Location

Investigational Site Number 8040001

Kyiv, 02125, Ukraine

Location

Investigational Site Number 8040006

Odesa, 65025, Ukraine

Location

Investigational Site Number 8040003

Ternopil, 46000, Ukraine

Location

Investigational Site Number 8040005

Vinnytsia, 21001, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 34302758 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

itepekimab; Standard of Care

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2018
• First Posted: June 6, 2018
• Study Start: July 16, 2018
• Primary Completion: October 3, 2019
• Study Completion: February 21, 2020
• Last Updated: November 22, 2022
• Results First Posted: November 22, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

PL (9); TU (6); UA (10); US (16); AU (6); AR (6); CL (6); RU (9); DE (6); CA (9)