Nebulized CSL787 (inhaled IgG) to reduce lung flare-ups in adults with non-cystic fibrosis bronchiectasis

A Phase 2b, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Dose Range Finding Study to Evaluate the Efficacy, Safety, and Tolerability of Nebulized CSL787 in Adults (18 to 85 Years) With Non-cystic Fibrosis Bronchiectasis

This research will test whether inhaled CSL787 (a nebulized immunoglobulin medicine) can delay or reduce lung flare-ups in adults with non-cystic fibrosis bronchiectasis over 6–12 months compared with placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 450 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: CSL Behring (Industry-sponsored)
• Locations: 13 sites (Queensland and 12 other locations)
• Trial ID: NCT07048262 on ClinicalTrials.gov

What this trial studies

This is a phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group dose-ranging study comparing two active dosing regimens of nebulized CSL787 versus placebo over 6 to 12 months. Adults with non-cystic fibrosis bronchiectasis confirmed by chest CT and with a recent history of exacerbations are eligible. Participants will inhale CSL787 or placebo via a nebulizer on a scheduled regimen while investigators record time to first pulmonary exacerbation, safety, and tolerability. The trial is designed to characterize dose response and the overall effect of inhaled CSL787 on prolonging time to first exacerbation.

Who should consider this trial

Good fit: Adults aged 18–85 with non-cystic fibrosis bronchiectasis confirmed by chest CT and a documented exacerbation history in the prior year (either ≥2 antibiotic-treated exacerbations, or 1 antibiotic-treated exacerbation plus an SGRQ Symptoms score >40) who can use a nebulizer are ideal candidates.

Not a fit: People without a recent history of exacerbations, those with cystic fibrosis, or patients already on chronic systemic immunoglobulin therapy or with contraindications to inhaled therapies are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, inhaled CSL787 could reduce the frequency or delay the onset of pulmonary exacerbations and lower the need for antibiotic treatments in people with non-CF bronchiectasis.

How similar studies have performed: Using inhaled immunoglobulin for bronchiectasis is a relatively novel approach and there are limited prior clinical data showing definitive success in this population.

Eligibility criteria

Inclusion Criteria:

* Adult between the ages of 18 to 85 years
* Primary diagnosis of NCFB confirmed by chest computed tomography (CT) scan, where bronchiectasis has been documented by a radiologist. Diagnosis in the medical records based on historical scans is acceptable if the chest CT scan confirming the participant's NCFB diagnosis was performed within 12 months before enrollment. Participants for whom no chest CT scan results are available within the previous 12 months will undergo a chest CT scan during the Screening Period
* Exacerbation history within the previous 1 year defined as either 1 of the following:
* \>= 2 documented exacerbations requiring oral and/or intravenous (IV) antibiotic therapy to treat a pulmonary infection.

OR

* 1 documented exacerbation requiring oral and/or IV antibiotic therapy to treat a pulmonary infection and a St. George's Respiratory Questionnaire (SGRQ) Symptoms score of \> 40 at Screening.
* Note: Other medications to treat NCFB such as: oral macrolides, or dipeptidyl peptidase-1 (DPP-1) inhibitors are allowed, provided \>= 1 historical exacerbation occurred while on the medication for \>= 3 months at a stable dose.
* Postbronchodilator percentage of the predicted normal forced expiratory volume in 1 second of expiration \[FEV1% predicted\] \> 35% and forced expiratory volume in 1 second (FEV1) \>= 1 liter (L) obtained in accordance with American Thoracic Society (ATS) / European Respiratory Society (ERS) standards for spirometry during Screening and at Baseline.

Exclusion Criteria:

* History of bronchospasm in response to inhaled therapies including inhaled antibiotics
* Known or suspected hypersensitivity, or other severe reactions, to the investigational product (IP), to any excipients of the IP, or to other immunoglobulin.
* Primary diagnosis of other pulmonary disorders, including chronic obstructive pulmonary disease (COPD) asthma or, diffuse panbronchiolitis (DPB), as determined by the investigator.
* Pulmonary exacerbation requiring antibiotic therapy within the 4 weeks before Baseline.

Where this trial is running

Queensland and 12 other locations

• The Prince Charles Hospital — Queensland, Australia (Recruiting)
• Westmead Hospital — Westmead, Australia (Recruiting)
• Fukuoka University Chikushi Hopsital — Chikushino-shi, Japan (Recruiting)
• Kyusho Central Hospital of the Mutual Aid Association of Public School Teachers — Fukuoka, Japan (Recruiting)
• Ibaraki Prefectural Central Hospital — Ibaraki, Japan (Recruiting)
• Kazunori Tobino Iizuka Hospital — Iizuka-shi, Japan (Recruiting)
• National Hospital Organization Minami Kyoto Hospital — Kyoto, Japan (Recruiting)
• Matsusaka Municipal Hospital — Mie, Japan (Recruiting)
• National Hospital Organization Kinki Chuo Chest Medical Center — Osaka, Japan (Recruiting)
• Shimonoseki City Hospital — Shimonoseki-shi, Japan (Recruiting)
• Japan Anti-Tuberculosis Association, Fukujuji Hospital — Tokyo, Japan (Recruiting)
• Keio University Hospital — Tokyo, Japan (Recruiting)
• National Hospital Organization Mie Chuo Medical Center — Tsu, Japan (Recruiting)

Study contacts

• Study coordinator: Trial Registration Coordinator

Conditions Non-cystic Fibrosis Bronchiectasis; Chronic respiratory disease; Inflammation; Chronic bacterial infection