Global Phase II Arthritis Trial With Quantitative Joint Imaging

Challenge

A global Phase II trial investigated the safety and efficacy of a new pharmaceutical compound for arthritis, with imaging endpoints measuring structural progression in affected joints. Radiographic scoring of erosion and joint space narrowing and MRI assessment of synovitis, bone marrow edema and erosion are reader-intensive, semi-quantitative and sensitive to positioning and acquisition technique.

The sponsor needed consistent scoring across readers and timepoints to detect a treatment effect on slow structural change within a Phase II timeframe, and a protocol that sites with varied musculoskeletal imaging experience could execute reliably.

Intrinsic Imaging’s Solution

Intrinsic Imaging's musculoskeletal team developed the imaging charter with standardized radiographic positioning for hands and feet and a joint MRI protocol specifying sequences, coverage and contrast use, and qualified sites with test acquisitions reviewed for positioning and image quality.

Fellowship-trained musculoskeletal radiologists scored radiographs for erosion and joint space narrowing and MRI for synovitis, bone marrow edema and erosion under validated semi-quantitative systems, reading each patient's complete timepoint series together with chronological order known, as the scoring methods specify. Independent double reads were performed on all patients with adjudication of score discrepancies above a predefined threshold.

Calibration sessions were held before and during the trial, reader agreement was monitored, and quality control at receipt verified positioning so that re-acquisition could occur within protocol windows.

Intrinsic Imaging’s Results

• Standardized radiographic and MRI acquisition implemented at 34 sites in 10 countries with site-level positioning feedback
• Approximately 1,400 radiographic and MRI examinations scored under validated semi-quantitative systems with independent double reads
• Inter-reader reliability for total structural score documented with an intraclass correlation above 0.90
• Unevaluable examinations held under 4% through central quality control and in-window re-acquisition