Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD

NCT05326412 | Completed Phase 2 DMC FDA Drug

• 4 other identifiers: PDY16967U1111-1255-53222024-512007-39-002021-001654-65
• Study Type: interventional
• Target: 49
• Locations: 7 countries
• Sites: 28

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

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (3)

• Change from baseline in itepekimab pharmacodynamic normalized enrichment score (NES) derived from former smokers in endobronchial biopsies in current smokers with COPD

  As measured by RNA sequencing, in former and current smokers with COPD

  Baseline to Week 12

• Change from baseline in itepekimab pharmacodynamic NES derived from former smokers in bronchial brushings in current smokers with COPD

  As measured by RNA sequencing, in former and current smokers with COPD

  Baseline to Week 12

• Change from baseline in itepekimab pharmacodynamic NES derived from former smokers in nasal brushings in current smokers with COPD

  As measured by RNA sequencing, in former and current smokers with COPD

  Baseline to Week 12

Secondary Outcomes (7)

• Change from baseline in IL-33 treated eosinophil-associated NES in endobronchial biopsies

  Baseline to Week 12

• Change from baseline in IL-33 treated mast cell-associated NES in endobronchial biopsies

  Baseline to Week 12

• Change from baseline in blood eosinophil count

  Baseline to Week 12

• 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

  Baseline up to end of study (EOS) (Week 32)

• Incidence of potentially clinically significant abnormalities in clinical laboratory tests, vital signs and electrocardiogram (ECG) abnormalities in the treatment-emergent period

  Baseline up to EOS (Week 32)

Study Arms (1)

Itepekimab

EXPERIMENTAL

This arm includes participants from 2 populations: Part A-former smokers and Part B-current smokers. Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for 12 weeks

Drug: Itepekimab SAR440340

Interventions

Itepekimab SAR440340 DRUG

Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: subcutaneous

Also known as: REGN3500

Itepekimab

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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).

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (28)

UCLA Medical Center - Harbor- Site Number : 8400006

Torrance, California, 90509, United States

Location

National Jewish Health Medical Center- Site Number : 8400012

Denver, Colorado, 80206, United States

Location

University of Miami UHealth Tower- Site Number : 8400015

Miami, Florida, 33125, United States

Location

Harvard Medical School - Massachusetts General Hospital (MGH) - Medical Practice Evaluation Center (MPEC)- Site Number : 8400007

Boston, Massachusetts, 02114, United States

Location

Pulmonary and Medicine Associates- Site Number : 8400020

Warren, Michigan, 48088, United States

Location

University of Kansas Medical Center- Site Number : 8400004

Kansas City, Missouri, 66160, United States

Location

Allergy, Asthma and Clinical Research- Site Number : 8400010

Oklahoma City, Oklahoma, 73120, United States

Location

Clinical Research Associates of Central PA - Dubois- Site Number : 8400011

DuBois, Pennsylvania, 15801, United States

Location

Penn Medicine: University of Pennsylvania Health System- Site Number : 8400016

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas - Southwestern Medical Center- Site Number : 8400014

Dallas, Texas, 75390, United States

Location

University of Texas Medical Branch- Site Number : 8400001

Galveston, Texas, 77555, United States

Location

Investigational Site Number : 0560001

Edegem, 2650, Belgium

Location

Hospital Parana- Site Number : 0760009

Maringá, Paraná, 87015-000, Brazil

Location

Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760003

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Hospital e Maternidade Celso Pierro - PUC-Campinas- Site Number : 0760004

Campinas, São Paulo, 13034-685, Brazil

Location

Integral Pesquisa e Ensino- Site Number : 0760006

Votuporanga, São Paulo, 15501-405, Brazil

Location

Hospital Beneficência Portuguesa de São Paulo- Site Number : 0760005

São Paulo, 01323-001, Brazil

Location

Investigational Site Number : 2080003

Aalborg, 9000, Denmark

Location

Investigational Site Number : 2080001

Copenhagen, 2400, Denmark

Location

Investigational Site Number : 2080002

Hvidovre, 2650, Denmark

Location

Investigational Site Number : 2760005

Freiburg im Breisgau, 79106, Germany

Location

Investigational Site Number : 2760001

Großhansdorf, 22927, Germany

Location

Investigational Site Number : 2760004

Peine, 31224, Germany

Location

Investigational Site Number : 5280001

Groningen, 9713 GR, Netherlands

Location

Investigational Site Number : 8260003

Wythenshawe, Cheshire West And Chester, M23 9QZ, United Kingdom

Location

Investigational Site Number : 8260004

London, London, City of, W2 1NY, United Kingdom

Location

Investigational Site Number : 8260001

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Investigational Site Number : 8260002

Liverpool, L9 7AL, United Kingdom

Location

Related Links

• PDY16967 Plain Language Results Summary

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

itepekimab

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2022
• First Posted: April 13, 2022
• Study Start: May 19, 2022
• Primary Completion: March 5, 2025
• Study Completion: July 25, 2025
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); BE (1); US (11); BR (5); DK (3); NL (1); GB (4)