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

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

18 Jun 2024 → 3 Feb 2026

Decision date (initial)

2024-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2023-508663-70-00

WHO UTN

U1111-1295-3237

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Pharmacodynamic, Pharmacoeconomic, Pharmacokinetic, Safety, Pharmacogenomic, Therapy, Pharmacogenetic

Evaluate the efficacy of itepekimab compared with placebo on occurrence of pulmonary exacerbations (PEs) in non-cystic fibrosis bronchiectasis (NCFB)

Secondary objectives 7

1. Evaluate the efficacy of itepekimab compared with placebo on occurrence of PEs in NCFB
2. Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in NCFB
3. Evaluate the efficacy of itepekimab compared with placebo on reduction in antibiotic use in NCFB
4. Evaluate the efficacy of itepekimab compared with placebo on health-related quality of life (HRQoL) and health status as assessed by Quality-of-Life Questionnaire – Bronchiectasis (QoL-B), and St. George’s Respiratory Questionnaire (SGRQ) in NCFB
5. Evaluate the safety and tolerability of itepekimab in NCFB
6. Evaluate the PK profile of itepekimab in NCFB
7. Evaluate immunogenicity to itepekimab in NCFB

Conditions and MedDRA coding

Bronchiectasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participant must be 18 to 85 years of age inclusive.
2. Clinical history consistent with NCFB (cough, chronic sputum production and/or recurrent respiratory infections).
3. Participants with a FEV1 % predicted ≥30%.
4. Participants with at least 2 moderate or 1 severe Pulmonary exacerbations (PEs) in the past 12 months.

Exclusion criteria 16

1. Have bronchiectasis due to CF, hypogammaglobulinemia, common variable immunodeficiency, known active nontuberculous mycobacteria (NTM) lung infection, or pulmonary fibrosis.
2. Known or suspected immunodeficiency disorder.
3. Pulmonary exacerbation which has not resolved clinically during screening period.
4. Have significant haemoptysis.
5. Have any clinically significant abnormal laboratory values at Screening or diseases or disorders.
6. History of lung transplantation.
7. History of malignancy within 5 years before Screening, or during the screening period
8. Currently being treated with antimicrobial therapy for tuberculosis (TB).
9. Currently on active treatment for allergic bronchopulmonary aspergillosis (ABPA).
10. Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease
11. Known allergy to itepekimab or to excipients
12. Live-attenuated vaccine(s) within 4 weeks prior to Screening or plans to receive such vaccines during the study
13. Unstable ischemic heart disease
14. Cardiomyopathy or other relevant cardiovascular disorder
15. Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening
16. History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of moderate or severe Pulmonary exacerbations (PEs) over the treatment period

Secondary endpoints 13

1. Time to first moderate or severe PE over the treatment period
2. Percentage of participants who are PE free over the treatment period
3. Annualized rate of severe PEs over the treatment period
4. Percentage of participants who are severe PE free over the treatment period
5. Time to first severe PE over the treatment period
6. Change From Baseline in FEV1 at Week 8 and Week 24
7. Number of days of new and/or added (in participants with maintenance antibiotic use) antibiotic use
8. Change from Baseline in QOL-B Respiratory Symptoms Domain Score in Adult Participants at Week 24
9. Change from baseline in SGRQ total score at Week 24
10. Percentage of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 24
11. Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent study treatment discontinuation in the treatment-emergent period
12. Serum concentrations of itepekimab from baseline to end of study
13. Incidence of treatment-emergent anti-itepekimab antibodies (ADA) responses throughout the study

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

1 Avenue Pierre Brossolette

City

Chilly-Mazarin

Postcode

91380

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 11

Locations

9 EU/EEA countries · 56 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 170 files

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

Application history

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