Phase 3 Evaluation of Itepekimab in Reducing Acute Exacerbations in Moderate-to-Severe Chronic Obstructive Pulmonary Disease in Former Smokers
- Trial ID
- 2024-512012-21-00
- Protocol
- EFC16819
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 in individuals with COPD.
Secondary objectives include:
- Evaluating the efficacy of itepekimab compared with placebo on pulmonary function, occurrence of acute exacerbation, severe exacerbations, and corticosteroid-treated exacerbations in former smokers with moderate-to-severe COPD.
- Assessing the efficacy on respiratory symptoms, Forced Expiratory Volume in 1 second (FEV1) slope, and health-related quality of life as assessed by St. George’s Respiratory Questionnaire (SGRQ).
- Evaluating the safety and tolerability of itepekimab, as well as its pharmacokinetic (PK) profile and immunogenicity in former smokers with moderate-to-severe COPD.
- Estimating the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate or severe COPD exacerbations, pulmonary function, safety and tolerability, PK profile, and immunogenicity in current smokers with moderate-to-severe COPD.
Participants
The clinical trial involves a total of **754 participants** diagnosed with **Chronic Obstructive Pulmonary Disease (COPD)**. The study population includes both male and female subjects, aged between 40 to 85 years, who have been diagnosed with moderate-to-severe COPD for at least one year. Participants are either former smokers with a history of at least 10 pack-years who have quit smoking at least six months prior to screening or current smokers who are not engaged in smoking cessation programs. The trial population was selected based on specific criteria, including a documented history of high exacerbation risk and a stable dose of standard controller therapy for at least one month prior to screening. Participants are required to have a body mass index (BMI) of at least 18.0 kg/m², or 16.0 kg/m² for those enrolled in East-Asian countries. Female participants are included if they are not pregnant or breastfeeding and adhere to contraceptive guidance if of child-bearing potential. The trial does not exclude vulnerable populations, ensuring a comprehensive evaluation of the intervention's efficacy across diverse demographic groups.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel-group Phase 3 study** 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. The trial is expected to last until September 2025, with participant recruitment having commenced in April 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 severity; multiple **follow-up visits** to monitor treatment effects and safety; and an **end-of-study visit** to assess final outcomes and collect data on any adverse events. Participants must be between 40 to 85 years of age, have a physician diagnosis of COPD for at least one year, and meet specific smoking history criteria. They 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 if they experience severe adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The study will measure primary endpoints such as the annualized rate of moderate or severe acute exacerbation of COPD in former smokers, and secondary endpoints including changes in lung function and respiratory symptoms, as well as the incidence of treatment-emergent adverse events. The trial will utilize a matched placebo for the test product, and itepekimab will be administered as a solution for injection in a pre-filled syringe via subcutaneous use.
Treatment
The clinical trial involves the administration of **Itepekimab**, a human monoclonal antibody targeting interleukin-33, which is being evaluated for its efficacy, safety, and tolerability in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Itepekimab is provided as a **solution for injection in a pre-filled syringe**. The route of administration is **subcutaneous use**, with a maximum daily dose of 300 mg and a total maximum dose of 7800 mg over a treatment period of up to 52 weeks. The pharmaceutical form is specifically designed for ease of administration and to ensure accurate dosing. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.
The study also includes a **matched placebo** for the test product, which serves as a comparator to evaluate the efficacy of Itepekimab. The placebo is designed to be indistinguishable from the active treatment in appearance and administration method, ensuring the double-blind nature of the trial. The placebo is administered via the same subcutaneous route and follows the same dosing schedule as the active treatment. This design allows for a rigorous assessment of the treatment's effects compared to the placebo, providing a robust evaluation of the therapeutic potential of Itepekimab in the target patient population.
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 changes in respiratory symptoms using the Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score and the St. George’s Respiratory Questionnaire (SGRQ) total score, as well as the incidence of treatment-emergent adverse events and other safety parameters.
Data collection will occur at specified timepoints throughout the trial, with assessments conducted using validated scales and laboratory tests. The trial will also monitor the functional concentrations of itepekimab in serum and the incidence of treatment-emergent anti-itepekimab antibody responses. These efficacy parameters will be analyzed to determine the therapeutic benefit of itepekimab compared to placebo, providing comprehensive insights into its potential as a treatment for COPD.
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: -- For former smokers: participants who report that they are not currently smoking and smoking cessation must have occurred ≥6 months prior to Screening (Visit 1A) with an intention to quit permanently. -- For current smokers: participants who report that they are currently smoking tobacco (participant smoked at least 1 cigarette per day on average during the past 7 days) at Screening (Visit 1A) and who are not currently participating in or planning to initiate a smoking cessation intervention at Screening (Visit 1A) or during Screening period.
- 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.
- For former smokers: Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).
- For current smokers: vaping of any products (eg, nicotine, 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 | 08 Apr 2021 | 161 |
 Czechia | Not Recruiting | 08 Apr 2021 | 89 |
 Estonia | Not Recruiting | 08 Apr 2021 | 1 |
 France | Not Recruiting | 08 Apr 2021 | 22 |
 Germany | Not Recruiting | 08 Apr 2021 | 149 |
 Hungary | Not Recruiting | 08 Apr 2021 | 85 |
 Lithuania | Not Recruiting | 08 Apr 2021 | 19 |
 The Netherlands | Not Recruiting | 08 Apr 2021 | — |
 Norway | Not Recruiting | 08 Apr 2021 | 3 |
 Poland | Not Recruiting | 08 Apr 2021 | 61 |
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 |
|---|---|---|---|---|---|---|
Matched placebo for test product | Placebo | N/A | — | — | — | N/A |
Itepekimab | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 300 | 52 | PRD10952832 |