Pivotal Phase II Biologic Trial in a Rare Degenerative Neuromuscular Disorder

Challenge

A pivotal Phase II trial of a novel biologic for a rare degenerative neuromuscular disorder relied on imaging biomarkers of muscle composition as key efficacy measures. Quantitative muscle MRI fat fraction and DXA lean mass are sensitive to scanner vendor, sequence implementation and positioning, and in a rare disease with small per-site enrollment, every patient's longitudinal data carried disproportionate weight.

The sponsor required measurement precision sufficient to detect slow changes over the treatment period, consistent muscle segmentation across readers and visits, and a protocol that patients with limited mobility could tolerate. Because the trial was pivotal, the imaging methodology also had to be documented to a standard suitable for regulatory review.

Intrinsic Imaging’s Solution

Intrinsic Imaging's musculoskeletal team designed the imaging charter around a quantitative MRI protocol, including Dixon-based fat-fraction sequences and defined anatomical coverage, with positioning aids and scan-time limits appropriate for patients with impaired mobility. Each of the 22 sites was qualified with phantom and volunteer scans, and DXA systems were cross-calibrated using a travelling phantom before enrollment.

Fellowship-trained musculoskeletal radiologists performed segmentation and fat-fraction analysis under a standardized reading charter, with the same reader following each patient longitudinally where possible and a second reader on a defined sample for reproducibility assessment. Qualitative review captured edema, atrophy and other structural change alongside the quantitative measures.

Project management maintained a per-patient imaging schedule across the trial, and quality control at receipt caught positioning and sequence deviations early enough for re-acquisition within protocol windows, protecting the small dataset from avoidable losses.

Intrinsic Imaging’s Results

• Quantitative MRI and DXA data acquired at 22 sites in 6 countries with vendor-neutral protocols and cross-calibrated DXA systems
• Fewer than 4% of imaging visits lost to unevaluable examinations in a rare-disease population where each visit was material to the analysis
• Intra- and inter-reader reproducibility of fat-fraction measurement documented on a prespecified sample, supporting the pivotal designation
• Complete regulatory-ready documentation of protocol, calibration, reader training and analysis methodology delivered with the final dataset