Chronic Obstructive Pulmonary DiseasePhase 2AERIFY-3NCT05326412
Mechanistic Study of the Effect of Itepekimab on Airway Inflammation in Patients With COPD
A Phase 2 study testing Itepekimab SAR440340 in people with Chronic Obstructive Pulmonary Disease, run by Sanofi at 23 sites in 7 countries.
Trial summary
This study was an exploratory, two-part, 12-week, Phase 2a study evaluated 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. Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Itepekimab SAR440340
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 23 sitesin 7 countries
- Study dates
- 19 May 2022to 25 Jul 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 reported that they were not currently smoking, and smoking cessation must had occurred ≥6 months prior to Screening (Visit 1) with an intention to quit permanently.
- For current smokers (not eligible for Part A): Participants who reported 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 were 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] had been excluded).
Show all 15Show fewer
- 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 were defined as an acute worsening of respiratory symptoms that required either systemic corticosteroids (intramuscular [IM], intravenous [IV], or oral) and/or antibiotics.
- Severe exacerbations were defined as AECOPD that required 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 had 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 was eligible to participate if she was not pregnant, not breastfed, and at least one of the following conditions applies:
- Not a women of child-bearing potential (WOCBP) or
- A WOCBP who agreed to follow the contraceptive guidance during the intervention period and for at least 20 weeks after the last dose of study intervention.
Who cannot join
- 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 were 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 might 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.
Show all 25Show fewer
- Participants who required more than 2 L/min of long-term treatment with oxygen at rest. Participants who used up to 4L/min of supplemental oxygen during exercise might enroll. Oxygen during sleep was allowed.
- Hypercapnia that required 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 were not exclusion criteria.
- Any surgery or major procedures (including those requiring conscious sedation) planned to occur during the study. Minor skin procedures were 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) might be considered for inclusion.
- Cardiomyopathy, as defined by Stage III-IV (New York Heart Association) cardiac failure, or other relevant cardiovascular disorder that that might affect the participant's participation in the study.
- Any underlying disease required 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 were 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 had a COVID-19 infection before Screening (Visit 1) who had 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 might 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 was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
United States7 sites
University of Texas - Southwestern Medical Center- Site Number : 8400014
Dallas, Texas, 75390
National Jewish Health Medical Center- Site Number : 8400012
Denver, Colorado, 80206
Clinical Research Associates of Central PA - Dubois- Site Number : 8400011
DuBois, Pennsylvania, 15801
University of Kansas Medical Center- Site Number : 8400004
Kansas City, Missouri, 66160
University of Miami UHealth Tower- Site Number : 8400015
Miami, Florida, 33125
Allergy, Asthma and Clinical Research- Site Number : 8400010
Oklahoma City, Oklahoma, 73120
UCLA Medical Center - Harbor- Site Number : 8400006
Torrance, California, 90509
Brazil4 sites
Hospital e Maternidade Celso Pierro - PUC-Campinas- Site Number : 0760004
Campinas, São Paulo, 13059-900
Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760003
Porto Alegre, Rio Grande do Sul, 90610-000
Hospital Beneficência Portuguesa de São Paulo- Site Number : 0760005
São Paulo, 01323-900
Integral Pesquisa e Ensino- Site Number : 0760006
Votuporanga, São Paulo, 15501-405
United Kingdom4 sites
Investigational Site Number : 8260002
Liverpool, L9 7AL
Investigational Site Number : 8260004
London, London, City of, W2 1NY
Investigational Site Number : 8260001
Nottingham, Nottinghamshire, NG5 1PB
Investigational Site Number : 8260003
Wythenshawe, Cheshire West And Chester, M23 9QZ
Denmark3 sites
Investigational Site Number : 2080003
Aalborg, 9000
Investigational Site Number : 2080001
Copenhagen, 2400
Investigational Site Number : 2080002
Hvidovre, 2650
Germany3 sites
Investigational Site Number : 2760005
Freiburg im Breisgau, 79106
Investigational Site Number : 2760001
Großhansdorf, 22926
Investigational Site Number : 2760004
Peine, 31224
Netherlands1 site
Investigational Site Number : 5280001
Groningen, 9713 GZ
About this study
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)
This study was an exploratory, two-part, 12-week, Phase 2a study evaluated 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 consisted of participants who had 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 would 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).
Read more
Part A would consist of participants who were former smokers with COPD; Part B would consist of participants who were current smokers with COPD.
The total study duration for each part (Part A and Part B) was approximately 36 weeks:
- 4-week screening period
- 12-week treatment period
- 20-week followup period
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Itepekimab SAR440340
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Itepekimab SAR440340Drug
Also called REGN3500
Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Itepekimab SAR440340 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Endobronchial Biopsies in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Measured: Baseline (Week 0) and Week 12
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Bronchial Brushings in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Measured: Baseline (Week 0) and Week 12
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Nasal Brushings in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Measured: Baseline (Week 0) and Week 12
Secondary outcomes (11)
Change From Baseline in Interleukin-33 (IL-33) Treated Eosinophil-associated Normalized Enrichment Score in Endobronchial Biopsies at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). IL-33 treated eosinophil-associated gene signature is used to evaluate NES of endobronchial biopsies of former and current smokers, at baseline and Week 12. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Measured: Baseline (Week 0) and Week 12
Change From Baseline in Interleukin-33 Treated Mast Cell-associated Normalized Enrichment Score in Endobronchial Biopsies at Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). IL-33 treated mast cell-associated gene signature is used to evaluate NES of endobronchial biopsies of former and current smokers, at baseline and Week 12. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Measured: Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Blood Eosinophil Count
Blood samples were collected at specified timepoints to assess change in blood eosinophil count. Baseline was defined as the last available value before first dose of study treatment.
Measured: Baseline (Week 0) and Week 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Event of Special Interests (TEAESIs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Permanent Treatment Discontinuation
An AE was defined as any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. An AE of special interest (AESI) was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor was required. SAEs were defined as any AE that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs were defined as AEs that developed, worsened or became serious during TE period (from first study treatment administration up to end of study).
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology During the Treatment-emergent Period
Blood samples were collected to determine the PCSA in hematology during the TE period (from the first treatment administration up to the end of study). Here, Hb = hemoglobin; g/L = grams per liter; M = male; F = female; v/v= volume by volume; LC = leukocyte count; NB = non-black; B = black; ULN = upper limit of normal and EO = eosinophils. Only parameters in which any participant had abnormality are reported.
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry During the Treatment-emergent Period
Blood samples were collected to determine the PCSA in chemistry during the TE period (first treatment administration up to the end of study). Here, mmol/L = millimoles/liter; LLN = lower limit of normal; mg/L = milligrams/liter and mcmol/L = micromoles/liter. Only parameters in which any participant had abnormality are reported.
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Urinalysis During the Treatment-emergent Period
Urine samples were collected to determine the PCSA in urine during the TE period (from the first treatment administration up to the end of study).
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs During the Treatment-emergent Period
Participants were examined to determine the PCSA in vital signs during the TE period (from the first treatment administration up to the end of study). Here, SSBP = sitting systolic blood pressure; mmHg = millimeters of mercury; DFB = decrease from baseline and IFB = increase from baseline. Only parameters in which any participant had abnormality are reported.
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) During the Treatment-emergent Period
Single 12-lead ECGs were obtained to determine PCSA during the TE period (from the first treatment administration up to the end of study). Here, QTcB= QT interval corrected by Bazett's formula and QTcF= QT interval corrected by Fridericia formula. Only parameters in which any participant had abnormality are reported.
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) to Itepekimab
Blood samples were collected to evaluate antibodies to itepekimab in serum. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing.
Measured: From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Serum Concentrations of Functional Itepekimab
Blood samples were collected at specified timepoints to obtain serum concentrations of itepekimab.
Measured: Pre-dose at Weeks 0, 4, 12 and 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2022
- Study start19 May 2022
- Primary completion5 Mar 2025
- Study completion25 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05326412
- Sponsor's protocol ID
- PDY16967
- Other IDs
- U1111-1255-5322, 2024-512007-39-00, 2021-001654-65
- Acronym
- AERIFY-3
- Status last verified
- Aug 2026
- First submitted
- 6 Apr 2022
- Last updated
- 31 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org