Efficacy and Safety Evaluation of Itepekimab in Moderate-to-Severe Chronic Obstructive Pulmonary Disease in Former Smokers: A Phase 3 Randomized Controlled Trial
- Trial ID
- 2024-512013-41-00
- Protocol
- EFC16750
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe exacerbations in former smokers with moderate-to-severe **Chronic Obstructive Pulmonary Disease (COPD)**. This is clinically relevant as reducing the frequency of exacerbations can significantly improve patient outcomes and quality of life, as well as reduce healthcare utilization.
Secondary objectives include evaluating the efficacy of itepekimab compared with placebo on:
- pulmonary function,
- occurrence of acute exacerbation of COPD (AECOPD),
- severe AECOPD,
- corticosteroid-treated AECOPD,
- respiratory symptoms,
- Forced Expiratory Volume in 1 second (FEV1) slope,
- health-related quality of life (HRQoL) as assessed by St. George’s Respiratory Questionnaire (SGRQ),
- safety and tolerability,
- pharmacokinetic (PK) profile,
- immunogenicity to itepekimab.
Participants
The clinical trial involves a total of **1715 participants** diagnosed with **Chronic Obstructive Pulmonary Disease (COPD)**. The study population includes both male and female subjects, aged between **40 to 85 years**. Participants were selected based on a physician's diagnosis of COPD for at least one year, with a history of smoking of at least 10 pack-years, although they are not currently smoking and have ceased smoking at least six months prior to the screening. The trial specifically targets individuals with moderate-to-severe COPD who have a documented history of high exacerbation risk, defined by having experienced at least two moderate or one severe exacerbation in the year prior to screening. Participants are required to be on a stable dose of standard controller therapy for at least one month before screening. The study also considers lifestyle factors such as body mass index, requiring a BMI of at least 18.0 kg/m², or 16.0 kg/m² for those in East-Asian countries. Female participants must not be pregnant or breastfeeding and must adhere to contraceptive guidance if of child-bearing potential. The trial includes a vulnerable population, ensuring comprehensive representation of the COPD demographic.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled, parallel-group Phase 3 study** designed to evaluate the efficacy, safety, and tolerability of **itepekimab** in patients with moderate-to-severe **chronic obstructive pulmonary disease (COPD)**. The primary objective is to assess the efficacy of itepekimab compared to placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPD. The trial is expected to last until November 2025, with participant recruitment having commenced in March 2021.
Participants will be involved in the study for a maximum treatment period of 52 weeks. The study includes several key visits: an initial screening visit to determine eligibility based on criteria such as age, smoking history, and COPD diagnosis; regular follow-up visits to monitor health status, treatment adherence, and any adverse events; and an end-of-study visit to assess the overall outcomes and gather final data. The inclusion criteria require participants to be aged 40 to 85 years, have a physician diagnosis of COPD for at least one year, and a history of smoking with cessation at least six months prior to screening. Participants must also have a documented history of high exacerbation risk and be on stable standard-of-care controller therapy.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The study will utilize a matched placebo for the test product, and the administration route for itepekimab is subcutaneous injection. The primary endpoint is the annualized rate of moderate or severe acute exacerbation of COPD, with secondary endpoints including changes in forced expiratory volume, time to first exacerbation, and incidence of treatment-emergent adverse events. The trial aims to provide comprehensive data on the potential benefits and risks of itepekimab in managing COPD exacerbations.
Treatment
The clinical trial involves the administration of **Itepekimab**, a human monoclonal antibody targeting interleukin-33 (IL-33). Itepekimab is provided as a **solution for injection in a pre-filled syringe**. The pharmaceutical form is designed for **subcutaneous use**. The dosing regimen for Itepekimab involves a maximum daily dose of 300 mg, with a total maximum dose of 7800 mg over a treatment period of 52 weeks. The active substance, Itepekimab, is a protein-based therapeutic agent, specifically an anti-IL-33 IgG4 human monoclonal antibody. The product is developed by Sanofi Aventis Recherche et Développement (SAR) and is identified by the sponsor product code SAR440340.
The study also includes a **matched placebo** for the test product, which serves as the comparator treatment in this randomized, double-blind, placebo-controlled trial. The placebo is designed to match the test product in appearance and administration method, ensuring blinding is maintained throughout the study. The placebo does not contain any active pharmaceutical ingredients and is used to evaluate the efficacy and safety of Itepekimab in comparison to a non-active treatment. The administration schedule and route for the placebo are identical to those of Itepekimab, ensuring consistency in the treatment protocol.
Efficacy
The efficacy of **itepekimab** in the clinical trial will be assessed by evaluating the annualized rate of moderate or severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in former smokers with moderate-to-severe COPD. This primary endpoint will provide a direct measure of the treatment's impact on the frequency of exacerbations. Secondary endpoints will include changes from baseline in pre-bronchodilator and post-bronchodilator forced expiratory volume in 1 second (FEV1), time to first moderate or severe AECOPD, and the annualized rate of severe AECOPD. Additional secondary measures will assess the rate of corticosteroid-treated AECOPD, changes in the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score, and changes in the St. George's Respiratory Questionnaire (SGRQ) total score, including the proportion of participants achieving a clinically significant decrease in SGRQ score.
Data collection will involve validated scales and laboratory tests to ensure accuracy and reliability. The incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and adverse events leading to permanent treatment discontinuation will also be monitored. Functional itepekimab concentrations in serum and the incidence of treatment-emergent anti-itepekimab antibody responses will be evaluated to further understand the treatment's efficacy and safety profile. The trial is designed to provide comprehensive data on the efficacy of itepekimab in reducing COPD exacerbations and improving respiratory function and quality of life in the target population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 40 to 85 years of age inclusive.
- Physician diagnosis of COPD for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition).
- Smoking history of ≥10 pack-years, but who are not currently smoking, and smoking cessation must have occurred ≥6 months prior to Screening (Visit 1A) with an intention to quit permanently.
- Participants with moderate-to-severe COPD
- Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year prior to screening in a participant in whom other causes of chronic cough [eg, inadequately treated gastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis] has been excluded).
- Documented history of high exacerbation risk defined as having had ≥2 moderate or ≥1 severe exacerbations within the year prior to Screening (Visit 1A), with at least 1 exacerbation treated with systemic corticosteroids. At least one exacerbation must have occurred while participants were on their current controller therapy: -- Moderate exacerbations will be recorded by the Investigator and are defined as acute worsening of respiratory symptoms that requires either systemic corticosteroids (IM, IV, or oral) and/or antibiotics. -- Severe exacerbations will be recorded by the Investigator and are defined as AECOPD that require hospitalization or observation for >24 hours in emergency department/urgent care facility.
- Participants with standard of care controller therapy, for ≥3 months prior to Screening (Visit 1A) and at a stable dose of controller therapy for at least 1 month prior to the screening, including either: inhaled corticosteroid (ICS) + long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA) + LABA or LAMA + LABA + ICS.
- Body mass index (BMI) ≥18.0 kg/m^2, or BMI ≥16.0 kg/m2 for participants enrolled in East-Asian countries.
- Female participant 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 of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma unless asthma resolved before 18 years of age and has not recurred.
- Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).
- Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening (Visit 1A) 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 α-1 anti-trypsin deficiency, or another diagnosed pulmonary disease.
- Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.
- Hypercapnia requiring bilevel positive airway pressure (BiPAP).
- Moderate or severe exacerbation of COPD (AECOPD) within 4 weeks prior to Screening (Visit 1A).
- Prior history of / planned: lung pneumonectomy for any reason, or lung volume reduction procedures (including bronchoscopic volume reduction) for COPD. Note: Surgical biopsy, or segmentectomy, or wedge resection, or lobectomy for other diseases would not be excluded.
- Unstable ischemic heart disease, including acute myocardial infarction within the past 1 year prior to Screening, or unstable angina in the 6 months prior to Screening (Visit 1A).
- Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation.
- Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of anti-hypertensive 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 prior to Screening (Visit 1A).
- History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1A).
- Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or in contact with known exposure to COVID-19 at Screening (Visit 1A); known history of COVID-19 infection within 4 weeks prior to Screening (Visit 1A); history of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to Screening (Visit 1A); participants who have had a COVID-19 infection prior Screening (Visit 1A) 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 4 weeks before Screening (Visit 1A), significant viral infections within 4 weeks before Screening (Visit 1A) that may not have been treated with antiviral treatment (eg, influenza receiving only symptomatic treatment).
- Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis.
- History of malignancy within 5 years before Screening (Visit 1A), except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
- Previous use of itepekimab.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 22 Mar 2021 | 118 |
 Czechia | Not Recruiting | 22 Mar 2021 | 58 |
 Greece | Not Recruiting | 22 Mar 2021 | 53 |
 Hungary | Not Recruiting | 22 Mar 2021 | 68 |
 Italy | Not Recruiting | 22 Mar 2021 | 19 |
 Poland | Not Recruiting | 22 Mar 2021 | 110 |
 Romania | Not Recruiting | 22 Mar 2021 | 108 |
 Slovakia | Not Recruiting | 22 Mar 2021 | 152 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Itepekimab | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 300 | 52 | PRD10952832 |
Matched placebo for test product | Placebo | N/A | — | — | — | N/A |