International Phase III Cystic Fibrosis Trial With Structured Chest CT Scoring

Challenge

An international Phase III trial of an investigational drug for cystic fibrosis used chest imaging to assess the treatment's effect on lung pathophysiology. Structured CT scoring of bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacity and hyperinflation is reader-intensive and subjective, and in a population that includes children, radiation dose and breath-hold capability constrain acquisition.

The sponsor needed a scoring system applied consistently across readers and sites, a low-dose protocol with inspiratory and expiratory phases acceptable for pediatric participants, and documentation of reader reproducibility to support a structural endpoint in a registration trial.

Intrinsic Imaging’s Solution

Intrinsic Imaging developed the imaging charter with a low-dose chest CT protocol including inspiratory and expiratory acquisitions, age-adjusted dose parameters and spirometer-guided or coached breath-hold technique, and qualified sites with test acquisitions reviewed for inspiration level and motion.

A dedicated team of thoracic radiologists scored each examination under a structured, lobe-based system covering bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacities and air trapping. Reads were blinded and independent on a prespecified double-read sample, with calibration sessions before and during the trial.

Quality control at receipt verified inspiration level and expiratory phase, and the scored dataset was delivered with component and total scores for the sponsor's structural endpoint analysis.

Intrinsic Imaging’s Results

• Low-dose inspiratory and expiratory chest CT protocol implemented at 38 sites in 11 countries with age-adjusted dose parameters
• Approximately 1,300 examinations scored under a structured lobe-based system by a dedicated thoracic radiology team
• Inter-reader agreement on total CT score documented with an intraclass correlation above 0.85 on the double-read sample
• Inadequate inspiration or expiration identified at central quality control in about 7% of initial submissions and corrected through site feedback