Clinical trial NCT03546907: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-06-06
Enrollment: 343
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Annualized Rate of Moderate to Severe Acute Exacerbation Events in Chronic Obstructive Pulmonary Disease (AECOPD) Participants
timeFrame: From Baseline up to Week 52
Secondary outcomes:
measure: Average Change in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) From Baseline to Week 16 Through Week 24
timeFrame: From Baseline to Week 16 through Week 24
measure: Change From Baseline in Post-bronchodilator Forced Expiratory Volume (FEV1) in 1 Second at Week 24
timeFrame: Baseline, Week 24
measure: Time to First Moderate or Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)
timeFrame: From Baseline up to 52 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Investigational Site Number 8400002
state: California
city: Riverside
country: United States
facility: Investigational Site Number 8400003
state: California
city: Rolling Hills Estates
country: United States
facility: Investigational Site Number 8400006
state: California
city: Westminster
country: United States
facility: Investigational Site Number 8400015
state: California
city: Jacksonville
country: United States
facility: Investigational Site Number 8400013
state: Florida
city: Columbia
country: United States
facility: Investigational Site Number 8400012
state: Maryland
city: North Dartmouth
country: United States
facility: Investigational Site Number 8400016
state: Massachusetts
city: South Dartmouth
country: United States
facility: Investigational Site Number 8400020
state: Massachusetts
city: Minneapolis
country: United States
facility: Investigational Site Number 8400011
state: Minnesota
city: Jamaica
country: United States
facility: Investigational Site Number 8400005
state: New York
city: Chapel Hill
country: United States
facility: Investigational Site Number 8400019
state: North Carolina
city: Raleigh
country: United States
facility: Investigational Site Number 8400004
state: North Carolina
city: Medford
country: United States
facility: Investigational Site Number 8400001
state: Oregon
city: Philadelphia
country: United States
facility: Investigational Site Number 8400009
state: Pennsylvania
city: Plano
country: United States
facility: Investigational Site Number 8400007
state: Texas
city: Greenfield
country: United States
facility: Investigational Site Number 8400008
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320001
city: Caba
country: Argentina
facility: Investigational Site Number 0320005
city: Caba
country: Argentina
facility: Investigational Site Number 0320002
city: Caba
country: Argentina
facility: Investigational Site Number 0320004
city: Quilmes
country: Argentina
facility: Investigational Site Number 0320006
city: Rosario
country: Argentina
facility: Investigational Site Number 0320003
city: Bedford Park
country: Australia
facility: Investigational Site Number 0360005
city: Chermside
country: Australia
facility: Investigational Site Number 0360002
city: Clayton
country: Australia
facility: Investigational Site Number 0360004
city: Frankston
country: Australia
facility: Investigational Site Number 0360003
city: Kent Town
country: Australia
facility: Investigational Site Number 0360006
city: Murdoch
country: Australia
facility: Investigational Site Number 0360001
city: Burlington
country: Canada
facility: Investigational Site Number 1240002
city: Hamilton
country: Canada
facility: Investigational Site Number 1240009
city: Montreal
country: Canada
facility: Investigational Site Number 1240003
city: Montreal
country: Canada
facility: Investigational Site Number 1240001
city: Quebec
country: Canada
facility: Investigational Site Number 1240005
city: Saint-Charles-Borromée
country: Canada
facility: Investigational Site Number 1240006
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number 1240008
city: Vancouver
country: Canada
facility: Investigational Site Number 1240007
city: Victoriaville
country: Canada
facility: Investigational Site Number 1240004
city: Quillota
country: Chile
facility: Investigational Site Number 1520002
city: Santiago
country: Chile
facility: Investigational Site Number 1520001
city: Santiago
country: Chile
facility: Investigational Site Number 1520007
city: Santiago
country: Chile
facility: Investigational Site Number 1520004
city: Talcahuano
country: Chile
facility: Investigational Site Number 1520003
city: Talca
country: Chile
facility: Investigational Site Number 1520005
city: Berlin
country: Germany
facility: Investigational Site Number 2760006
city: Großhansdorf
country: Germany
facility: Investigational Site Number 2760001
city: Hamburg
country: Germany
facility: Investigational Site Number 2760002
city: Koblenz
country: Germany
facility: Investigational Site Number 2760007
city: München
country: Germany
facility: Investigational Site Number 2760004
city: Rüdersdorf Bei Berlin
country: Germany
facility: Investigational Site Number 2760005
city: Bialystok
country: Poland
facility: Investigational Site Number 6160001
city: Bialystok
country: Poland
facility: Investigational Site Number 6160008
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 6160005
city: Grudziadz
country: Poland
facility: Investigational Site Number 6160009
city: Krakow
country: Poland
facility: Investigational Site Number 6160007
city: Poznan
country: Poland
facility: Investigational Site Number 6160002
city: Poznan
country: Poland
facility: Investigational Site Number 6160006
city: Rzeszow
country: Poland
facility: Investigational Site Number 6160010
city: Znin
country: Poland
facility: Investigational Site Number 6160003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430010
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430006
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430007
city: Stavropol
country: Russian Federation
facility: Investigational Site Number 6430009
city: Ulyanovsk
country: Russian Federation
facility: Investigational Site Number 6430004
city: Ankara
country: Turkey
facility: Investigational Site Number 7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920001
city: Izmir
country: Turkey
facility: Investigational Site Number 7920006
city: Izmir
country: Turkey
facility: Investigational Site Number 7920007
city: Kirikkale
country: Turkey
facility: Investigational Site Number 7920008
city: Mersin
country: Turkey
facility: Investigational Site Number 7920002
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number 8040008
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 8040012
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 8040004
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040002
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040011
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040007
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040001
city: Odesa
country: Ukraine
facility: Investigational Site Number 8040006
city: Ternopil
country: Ukraine
facility: Investigational Site Number 8040003
city: Vinnytsya
country: Ukraine
facility: Investigational Site Number 8040005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.