Dose Range Finding, Efficacy, and Safety Study of Nebulized CSL787 in Adults With Non-cystic Fibrosis Bronchiectasis (NCFB)

Official title

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

Overview

This study is a phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose range finding study designed to explore the efficacy, safety, and tolerability of 2 active treatment regimens of CSL787 (immunoglobulin G \[IgG\] inhalation solution) compared with placebo over a period of 6 to 12 months independent of the occurrence of pulmonary exacerbations. The primary aim of the study is to characterize the overall effect of CSL787 as well as the dose response of 2 active treatment regimens of inhaled CSL787 administered to participants with NCFB toward prolonging the TTF exacerbation.

Interventions

• Biological CSL787
  CSL787 high or low doses once daily (QD) will be administered via inhalation over a period of 6 to 12 months.
• Drug Placebo
  Participants will receive a matching volume of placebo QD over a period of 6 to 12 months.
• Device Nebulizer
  The nebulizer is a CE-marked device.

Primary outcome measures

• Time to first (TTF) Exacerbation [Time frame: Up to Month 12]

Secondary outcome measures (7)

• Annualized Exacerbation Rate (AER) (Exacerbation Event Rate Per-participant Year) [Time frame: Up to Month 12]
• Number of Participants Achieving a Clinically Important Difference in the Quality of Life-Bronchiectasis (QoL-B) Respiratory Symptoms Scale [Time frame: Up to Month 12]
• Percentage of Participants Achieving a Clinically Important Difference in the QoL-B Respiratory Symptoms Scale [Time frame: Up to Month 12]
• Change From Baseline in QoL-B Respiratory Symptoms Scale [Time frame: From Baseline to Months 6 and 12]
• Change From Baseline in Total Colony-forming Unit (CFUs) for Pathogenic Bacteria Isolated from Sputum [Time frame: From Baseline to Month 1]
• Number of Participants with Treatment-emergent Adverse events (TEAEs) and Serious Adverse Events (SAEs) [Time frame: Up to Month 13]
• Percentage of Participants with TEAEs and SAEs [Time frame: Up to Month 13]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Japan · 11 centers

• Fukuoka University Chikushi Hopsital — Chikushino-shi
• Kyusho Central Hospital of the Mutual Aid Association of Public School Teachers — Fukuoka
• Ibaraki Prefectural Central Hospital — Ibaraki
• Kazunori Tobino Iizuka Hospital — Iizuka-shi
• National Hospital Organization Minami Kyoto Hospital — Kyoto
• Matsusaka Municipal Hospital — Mie
• National Hospital Organization Kinki Chuo Chest Medical Center — Osaka
• Shimonoseki City Hospital — Shimonoseki-shi
• … and 3 more centers

Australia · 2 centers

• The Prince Charles Hospital — Queensland
• Westmead Hospital — Westmead

Identifiers

NCT: NCT07048262 · CSL787_2001 · 2024-518821-13-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗