Clinical trial NCT05326412: Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD
Official title: A Phase 2a, Open-label, Two-part Study to Evaluate the Mechanism of Action of Itepekimab (Anti-IL-33 mAb) on Airway Inflammation in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2022-04-13
Enrollment: 49
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an exploratory, two-part, 12-week, Phase 2a study to evaluate the mechanism of action of Itepekimab (anti-IL-33-mAb) and its impact on airway inflammation in former and current smokers with COPD, aged 40 to 70 years.

This study consists of participants who have been on a standard-of-care (SoC) mono (long-acting β2-agonist \[LABA\]) or long-acting muscarinic antagonist \[LAMA\]), double (inhaled corticosteroid \[ICS\] + LABA, LABA + LAMA or ICS + LAMA), or triple (ICS + LABA + LAMA) controller therapy for COPD for at least 3 months prior to Screening (Visit 1) with stable dose and regimen for controller therapy for ≥1 month prior to Screening (Visit 1) and during the screening period. Participants will stay on their established controller medications for COPD throughout the duration of the study, with the exception of systemic corticosteroids and/or antibiotics used for acute exacerbation of COPD (AECOPD).

Part A will consist of participants who are former smokers with COPD; Part B will consist of participants who are current smokers with COPD.

The total study duration for each part (Part A and Part B) is approximately 36 weeks:

* 4-week screening period
* 12-week treatment period
* 20-week followup period


Eligibility criteria: Inclusion Criteria:

* Participant must be 40 to 70 years of age inclusive
* Physician diagnosis of COPD for at least 1 year (based on the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] definition).
* Smoking history of ≥10 pack-years

  * For former smokers: Participants who report that they are not currently smoking, and smoking cessation must have occurred ≥6 months prior to Screening (Visit 1) with an intention to quit permanently.
  * For current smokers (not eligible for Part A): Participants who report that they are currently smoking tobacco (participant smoked at least 5 cigarettes per day on average during the past 7 days) at Screening (Visit 1) and at Baseline, and who are not currently participating in, or planning to initiate, a smoking cessation intervention at Screening (Visit 1) or during the screening period.
* Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year before screening in a participant in whom other causes of chronic cough \[eg, inadequately treated gastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis\] have been excluded).
* Documented or self-reported history of exacerbation having had ≥1 moderate or severe exacerbation within the 5 years prior to Screening (Visit 1), with at least 1 exacerbation treated with systemic corticosteroids:

  * Moderate exacerbations are defined as an acute worsening of respiratory symptoms that requires either systemic corticosteroids (intramuscular \[IM\], intravenous \[IV\], or oral) and/or antibiotics.
  * Severe exacerbations are defined as AECOPD that require hospitalization or observation for \>24 hours in emergency department/urgent care facility.
* Participants treated with SoC controller therapy for ≥3 months before Screening (Visit 1) and at a stable dose and regimen of controller therapy for at least 1 month before the screening visit AND during the screening period, including either: triple therapy with LAMA + LABA + ICS or double therapy with ICS + LABA or LABA + LAMA or ICS + LAMA, or monotherapy with LABA or LAMA.
* Participants who have received appropriate vaccination according to local recommendations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), administered a minimum of 1 week prior to Screening (Visit 1).
* Body mass index (BMI) ≥18 kg/m2
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

  * Not a women of child-bearing potential (WOCBP) or
  * A WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 20 weeks after the last dose of study intervention.

Exclusion Criteria:

* Current diagnosis or previously confirmed diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines unless asthma resolved before 18 years of age and has not recurred.
* For former smokers (Parts A): Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol \[THC\]) within 6 months prior to Screening (Visit 1) or during the screening period. For current smokers (Part B): vaping of any products (eg, nicotine, THC) within 6 months prior to Screening (Visit 1) or during the screening period.
* Participants who are expected to be regularly exposed to environmental (ie, 'second hand') tobacco smoke in an indoor setting during the screening or treatment periods (former smokers only).
* Clinically significant new abnormal electrocardiogram (ECG) within 6 months before or at Screening (Visit 1) that may affect the participant's participation in the study.
* Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of α1 anti-trypsin deficiency, or another diagnosed pulmonary disease.
* Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.
* Participants who require more than 2 L/min of long-term treatment with oxygen at rest. Participants who use up to 4L/min of supplemental oxygen during exercise may enroll. Oxygen during sleep is allowed.
* Hypercapnia that requires bi-level positive airway pressure (BiPAP).
* Moderate or severe exacerbation of COPD (AECOPD) within 8 weeks prior to Screening (Visit 1) or during the screening period.
* Prior history of pneumonectomy, lobectomy, segmentectomy, or therapeutic bronchoscopy procedure (including bronchoscopic volume reduction). Note: Prior history of surgical lung biopsy or wedge resection are not exclusion criteria.
* Any surgery or major procedures (including those requiring conscious sedation) planned to occur during the study. Minor skin procedures are allowed.
* Unstable ischemic heart disease, including acute myocardial infarction within 1 year before Screening (Visit 1), or unstable angina within 6 months before Screening (Visit 1) or during the screening period.
* Cardiac arrhythmias, including paroxysmal (eg, intermittent) atrial fibrillation. Participants with isolated premature ventricular contractions (PVCs) or premature atrial contractions (PACs) may be considered for inclusion.
* Cardiomyopathy, as defined by Stage III-IV (New York Heart Association) cardiac failure, or other relevant cardiovascular disorder that that may affect the participant's participation in the study.
* Any underlying disease requiring the use of prophylaxis for endocarditis.
* Uncontrolled hypertension (ie, systolic blood pressure \[BP\] \>180 mm Hg or diastolic BP \>110 mm Hg with or without use of antihypertensive therapy).
* Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection (TBI), or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette Guérin (BCG)-vaccination within 12 weeks before Screening (Visit 1).
* History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1).
* Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or contact with known exposure to COVID19 at Screening (Visit 1) or during the screening period; known history of COVID19 infection within 6 weeks before Screening (Visit 1); history of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 12 months before Screening (Visit 1); participants who have had a COVID-19 infection before Screening (Visit 1) who have not yet sufficiently recovered to participate in the procedures of a clinical trial.
* Evidence of acute or chronic infection requiring systemic treatment with antibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medications within 6 weeks before Screening (Visit 1) or during the screening period, significant viral infections within 6 weeks before Screening (Visit 1) or during the screening period that may not have been treated with antiviral treatment (eg, influenza receiving only symptomatic treatment).
* Participants with active autoimmune disease or participants taking immunosuppressive therapy for autoimmune disease (eg, rheumato arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).
* History of malignancy within 5 years before Screening (Visit 1), or during the screening period, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
* Symptomatic herpes zoster within 3 months prior to screening.
* Previous use of Itepekimab.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Change from baseline in itepekimab pharmacodynamic normalized enrichment score (NES) derived from former smokers in endobronchial biopsies in current smokers with COPD
timeFrame: Baseline to Week 12
measure: Change from baseline in itepekimab pharmacodynamic NES derived from former smokers in bronchial brushings in current smokers with COPD
timeFrame: Baseline to Week 12
measure: Change from baseline in itepekimab pharmacodynamic NES derived from former smokers in nasal brushings in current smokers with COPD
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change from baseline in IL-33 treated eosinophil-associated NES in endobronchial biopsies
timeFrame: Baseline to Week 12
measure: Change from baseline in IL-33 treated mast cell-associated NES in endobronchial biopsies
timeFrame: Baseline to Week 12
measure: Change from baseline in blood eosinophil count
timeFrame: Baseline to Week 12
measure: Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interests (AESIs), serious adverse events (SAEs), and adverse events (AEs) leading to permanent treatment discontinuation
timeFrame: Baseline up to end of study (EOS) (Week 32)
measure: Incidence of potentially clinically significant abnormalities in clinical laboratory tests, vital signs and electrocardiogram (ECG) abnormalities in the treatment-emergent period
timeFrame: Baseline up to EOS (Week 32)
measure: Incidence of treatment-emergent anti-itepekimab antibody responses throughout the study
timeFrame: Baseline up to EOS (Week 32)
measure: Functional itepekimab concentrations in serum
timeFrame: Baseline up to EOS (Week 32)
Other outcomes:
Locations:
city: Torrance
country: United States
facility: UCLA Medical Center - Harbor- Site Number : 8400006
state: California
city: Denver
country: United States
facility: National Jewish Health Medical Center- Site Number : 8400012
state: Colorado
city: Miami
country: United States
facility: University of Miami UHealth Tower- Site Number : 8400015
state: Florida
city: Boston
country: United States
facility: Harvard Medical School - Massachusetts General Hospital (MGH) - Medical Practice Evaluation Center (MPEC)- Site Number : 8400007
state: Massachusetts
city: Warren
country: United States
facility: Pulmonary and Medicine Associates- Site Number : 8400020
state: Michigan
city: Kansas City
country: United States
facility: University of Kansas Medical Center- Site Number : 8400004
state: Missouri
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research- Site Number : 8400010
state: Oklahoma
city: DuBois
country: United States
facility: Clinical Research Associates of Central PA - Dubois- Site Number : 8400011
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System- Site Number : 8400016
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas - Southwestern Medical Center- Site Number : 8400014
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch- Site Number : 8400001
state: Texas
city: Edegem
country: Belgium
facility: Investigational Site Number : 0560001
city: Maringá
country: Brazil
facility: Hospital Parana- Site Number : 0760009
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760003
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Hospital e Maternidade Celso Pierro - PUC-Campinas- Site Number : 0760004
state: São Paulo
city: Votuporanga
country: Brazil
facility: Integral Pesquisa e Ensino- Site Number : 0760006
state: São Paulo
city: São Paulo
country: Brazil
facility: Hospital Beneficência Portuguesa de São Paulo- Site Number : 0760005
city: Aalborg
country: Denmark
facility: Investigational Site Number : 2080003
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Hvidovre
country: Denmark
facility: Investigational Site Number : 2080002
city: Freiburg
country: Germany
facility: Investigational Site Number : 2760005
city: GROßHANSDORF
country: Germany
facility: Investigational Site Number : 2760001
city: Peine
country: Germany
facility: Investigational Site Number : 2760004
city: Groningen
country: Netherlands
facility: Investigational Site Number : 5280001
city: Wythenshawe
country: United Kingdom
facility: Investigational Site Number : 8260003
state: Cheshire West And Chester
city: London
country: United Kingdom
facility: Investigational Site Number : 8260004
state: London, City Of
city: Nottingham
country: United Kingdom
facility: Investigational Site Number : 8260001
state: Nottinghamshire
city: Liverpool
country: United Kingdom
facility: Investigational Site Number : 8260002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: