Bronchiectasis
Conditions
Brief summary
ACT18018 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study with 3 treatment groups. The purpose of this study is to evaluate efficacy, safety and tolerability with 2 dosing regimens of itepekimab compared with placebo in male and/or female participants with NCFB aged 18 years of age up to 85 years of age (inclusive). Study details include: * The study duration (screening, 24-52-week treatment, 20-week safety follow-up) will be up to 47-77 weeks. * The treatment duration will be up to 24-52 weeks. * The follow-up duration will be 20 weeks. * Site/phone visits are at a monthly interval.
Interventions
Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous
DRUGPlacebo
Pharmaceutical form: solution for injection in pre-filled syringe. Route of administration: subcutaneous
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 to 85 years of age inclusive. * Clinical history consistent with NCFB (cough, chronic sputum production and/or recurrent respiratory infections). * Participants with a FEV1 % predicted ≥30%. * Participants with at least 2 moderate or 1 severe Pulmonary exacerbations (PEs) in the past 12 months.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Have bronchiectasis due to CF, hypogammaglobulinemia, common variable immunodeficiency, known active nontuberculous mycobacteria (NTM) lung infection, or pulmonary fibrosis. * Known or suspected immunodeficiency disorder. * Pulmonary exacerbation which has not resolved clinically during screening period. * Have significant haemoptysis. * Have any clinically significant abnormal laboratory values at Screening or diseases or disorders. * History of lung transplantation. * History of malignancy within 5 years before Screening, or during the screening period * Currently being treated with antimicrobial therapy for tuberculosis (TB). * Currently on active treatment for allergic bronchopulmonary aspergillosis (ABPA). * Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease * Known allergy to itepekimab or to excipients * Live-attenuated vaccine(s) within 4 weeks prior to Screening or plans to receive such vaccines during the study * Unstable ischemic heart disease * Cardiomyopathy or other relevant cardiovascular disorder * Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening * History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized rate of moderate or severe Pulmonary exacerbations (PEs) over the treatment period | Baseline up to End of Treatment (EOT) (24-52 weeks) | Annualized rate of moderate or severe PEs over the placebo-controlled treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first moderate or severe PE over the treatment period | Baseline up to End of Treatment (EOT) (24-52 weeks) | — |
| Percentage of participants who are PE free over the treatment period | Baseline up to End of Treatment (EOT) (24-52 weeks) | — |
| Annualized rate of severe PEs over the treatment period | Baseline up to End of Treatment (EOT) (24-52 weeks) | — |
| Percentage of participants who are severe PE free over the treatment period | Baseline up to End of Treatment (EOT) (24-52 weeks) | — |
| Time to first severe PE over the treatment period | Baseline up to End of Treatment (EOT) (24-52 weeks) | — |
| Change From Baseline in FEV1 at Week 8 and Week 24 | Week 8 and Week 24 | FEV1 is force expiratory volume in 1 second |
| Number of days of new and/or added (in participants with maintenance antibiotic use) antibiotic use | Baseline up to End of Treatment (EOT) (24-52 weeks) | — |
| Change from Baseline in QOL-B Respiratory Symptoms Domain Score in Adult Participants at Week 24 | Week 24 | The Quality-Of-Life-Bronchiectasis (QOL-B) is a validated, self-administered patient reported outcome (PRO) that assesses symptoms, functioning and health-related QOL for subjects with NCFB. |
| Change from baseline in SGRQ total score at Week 24 | Week 24 | The St. George's Respiratory Questionnaire (SGRQ) is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. |
| Percentage of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 24 | Week 24 | The St. George's Respiratory Questionnaire (SGRQ) is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. |
| Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent study treatment discontinuation in the treatment-emergent period | Baseline up to End of Study (EOS) (44 to 72 weeks) | — |
| Serum concentrations of itepekimab from baseline to end of study | Baseline up to End of Study (EOS) (44 to 72 weeks) | — |
| Incidence of treatment-emergent anti-itepekimab antibodies (ADA) responses throughout the study | Baseline up to End of Study (EOS) (44 to 72 weeks) | — |
Countries
Argentina, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Netherlands, Poland, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed