Mechanistic study of the effect of itepekimab on airway inflammation in patients with COPD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

20 Jun 2022 → 25 Jul 2025

Decision date (initial)

2024-05-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2024-512007-39-00

EudraCT number

2021-001654-65

WHO UTN

U1111-1255-5322

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacodynamic, Pharmacokinetic, Pharmacogenomic, Therapy, Safety

Evaluate the difference in gene expression between former and current smokers with itepekimab treatment

Secondary objectives 2

1. Evaluate in former and current smokers with COPD the: • effect of itepekimab treatment on prespecified cell type-associated gene expression signatures in endobronchial biopsies, • effect of itepekimab on blood eosinophil counts, • safety and tolerability of itepekimab, • immunogenicity to itepekimab in serum.
2. PK profile of itepekimab in serum

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be 40 to 70 years of age inclusive
2. Physician diagnosis of COPD for at least 1 year (based on the Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition)
3. Smoking history of ≥10 pack-years; a) 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, b) 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
4. 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).
5. 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: a) 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. b) Severe exacerbations are defined as AECOPD that require hospitalization or observation for >24 hours in emergency department/urgent care facility.
6. 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
7. 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)
8. Body mass index (BMI) ≥18 kg/m2
9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Not a women of child-bearing potential (WOCBP) or b) 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 24

1. Participants are excluded from the study if any of the following criteria apply: - 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
2. For former smokers (Part 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
3. 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)
4. 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
5. Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of α 1 anti-trypsin deficiency, or another diagnosed pulmonary disease
6. Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension
7. 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
8. Hypercapnia that requires bi-level positive airway pressure (BiPAP)
9. Moderate or severe exacerbation of COPD (AECOPD) within 8 weeks prior to Screening (Visit 1) or during the screening period
10. 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
11. Any surgery or major procedures (including those requiring conscious sedation) planned to occur during the study. Minor skin procedures are allowed
12. 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
13. 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
14. 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
15. Any underlying disease requiring the use of prophylaxis for endocarditis
16. Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of antihypertensive therapy)
17. 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)
18. History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1)
19. Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or contact with known exposure to COVID 19 at Screening (Visit 1) or during the screening period; known history of COVID 19 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
20. 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)
21. Participants with active autoimmune disease or participants taking immunosuppressive therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis)
22. 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
23. Symptomatic herpes zoster within 3 months prior to screening
24. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Change from baseline in itepekimab pharmacodynamic normalized enrichment score (NES) derived from former smokers in endobronchial biopsies in current smokers with COPD
2. Change from baseline in itepekimab pharmacodynamics NES derived from former smokers in bronchial brushings in current smokers with COPD
3. Change from baseline in itepekimab pharmacodynamics NES derived from former smokers in nasal brushings in current smokers with COPD

Secondary endpoints 7

1. Change from baseline in IL-33 treated eosinophil-associated NES in endobronchial biopsies
2. Change from baseline in IL-33 treated mast cell-associated NES in endobronchial biopsies
3. Change from baseline in blood eosinophil count
4. 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
5. Incidence of potentially clinically significant abnormalities in clinical laboratory tests, vital signs and electrocardiogram (ECG) abnormalities in the treatment-emergent period
6. Incidence of treatment-emergent anti-itepekimab antibody responses throughout the study
7. Functional itepekimab concentrations in serum

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 7

Locations

4 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications