A Proof-of-Concept study to assess the efficacy, safety and tolerability of itepekimab (anti-IL-33 mAb) in participants with non-cystic fibrosis bronchiectasis

JRCT ID: jRCT2031240053

Registered date:26/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Bronchiectasis
• Date of first enrollment: 13/05/2024
• Target sample size: 300
• Countries of recruitment: United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Itepekimab (SAR440340, REGN3500)
Pharmaceutical form: solution for injection in pre-filled syringe, Route of administration: subcutaneous
Drug: Placebo
Pharmaceutical form: solution for injection in pre-filled syringe, Route of administration: subcutaneous

Study Arms:
- Experimental: Itepekimab every 2 weeks (Q2W)
Subcutaneous (SC) administration of Itepekimab Q2W for up to 52 weeks.
- Experimental: Itepekimab every 4 weeks (Q4W)
SC administration of Itepekimab Q4W with alternating placebo administration at the 2week interval between active investigational medicinal product (IMP) as SC injection for up to 52 weeks.
- Placebo Comparator: Placebo
SC administration of matching placebo Q2W for up to 52 weeks.

Outcome(s)

Primary Outcome

1. Annualized rate of moderate or severe Pulmonary exacerbations (PEs) over the treatment period
[Time Frame: Baseline up to End of Treatment (EOT) (24-52 weeks)]
Annualized rate of moderate or severe PEs over the placebo-controlled treatment period.

Secondary Outcome

1. Time to first moderate or severe PE over the treatment period
[Time Frame: Baseline up to EOT (24-52 weeks)]
2. Percentage of participants who are PE free over the treatment period
[Time Frame: Baseline up to EOT (24-52 weeks)]
3. Annualized rate of severe PEs over the treatment period
[Time Frame: Baseline up to EOT (24-52 weeks)]
4. Percentage of participants who are severe PE free over the treatment period
[Time Frame: Baseline up to EOT (24-52 weeks)]
5. Time to first severe PE over the treatment period
[Time Frame: Baseline up to EOT (24-52 weeks)]
6. Change From Baseline in FEV1 at Week 8 and Week 24
[Time Frame: Week 8 and Week 24]
FEV1 is force expiratory volume in 1 second.
7. Number of days of new and/or added (in participants with maintenance antibiotic use) antibiotic use
[Time Frame: Baseline up to EOT (24-52 weeks)]
8. Change from Baseline in Quality-Of-Life-Bronchiectasis (QOL-B) Respiratory Symptoms Domain Score in Adult Participants at Week 24
[Time Frame: Week 24]
The QOL-B is a validated, self-administered patient reported outcome (PRO) that assesses symptoms, functioning and health-related QOL for subjects with NCFB.
9. Change from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score at Week 24
[Time Frame: Week 24]
SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
10. Percentage of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 24
[Time Frame: Week 24]
Refer to the secondary outcome-9 for "SGRQ".
11. Incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and adverse events (AEs) leading to permanent study treatment discontinuation in the treatment-emergent period
[Time Frame: Baseline up to End of Study (EOS) (44 to 72 weeks)]
12. Serum concentrations of itepekimab from baseline to end of study
[Time Frame: Baseline up to EOS (44 to 72 weeks)]
13. Incidence of treatment-emergent anti-itepekimab antibodies (ADA) responses throughout the study
[Time Frame: Baseline up to EOS (44 to 72 weeks)]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 85age old
• Gender: Both

Include 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 forced expiratory volume in 1 second (FEV1) % predicted >= 30%.
- Participants with at least 2 moderate or 1 severe Pulmonary exacerbations (PEs) in the past 12 months.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Have bronchiectasis due to cystic fibrosis, hypogammaglobulinemia, common variable immunodeficiency, known active nontuberculous mycobacteria 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.
- Currently on active treatment for allergic bronchopulmonary aspergillosis.
- 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06280391,2023-508663-70