Evaluation of disease progression rate in progressive supranuclear palsy using MRI biomarkers: new implications for clinical trials

Lead Investigator: Andrea Quattrone, Magna Graecia University of Catanzaro
Title of Proposal Research: Evaluation of disease progression rate in progressive supranuclear palsy using MRI biomarkers: new implications for clinical trials
Vivli Data Request: 6003
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Progressive supranuclear palsy (PSP) is a severe neurodegenerative disease and its prevalence has been increasing during the last decades. Up to date, no approved disease-modifying drugs exist, but several therapeutic strategies are under development. Clinical rating scales are often considered as the primary endpoint to assess efficacy in clinical trials in PSP. Clinical data, however, are difficult to standardize across centers and may be subject to day-to-day variability. Thus, there is an urgent need for objective and validated biomarkers that can track the progression of the disease and may serve as outcome measures. A recent study has demonstrated that Magnetic Resonance Parkinsonism Index 2.0 (MRPI 2.0), a well-known morphometric MRI biomarker for PSP based on the measurement of the brain structures mainly involved in this disease, was more powerful than clinical scales in tracking PSP progression, with higher effect size and smaller sample size. A longitudinal study in a large independent international PSP cohort, however, is warranted to confirm these preliminary results.

The randomized, placebo-controlled, phase II trial of ABBV-8E12 (M15-562, clinicaltrials.gov: NCT02985879) studied 378 PSP patients for 12 months. Their placebo data would provide the needed information to evaluate the performances of MRPI 2.0 in tracking the worsening of the disease in comparison with clinical scores. This project could allow to confirm the potential usefulness of MRPI 2.0 as an objective and reliable biomarker of disease progression overcoming the current limitations of clinical scales, with implications of global interest for clinical trials in PSP. Also, it would be of interest to evaluate if any difference exists between the two arms of the M15-562 trial using MRPI 2.0 as secondary endpoint. Morphometric imaging biomarkers, such as MRPI 2.0, are objective measurements with higher sensitivity and lower variability than clinical scales. Thus, it is not possible to exclude that significant difference between the two patient groups of the M15-562 study exist, detectable by MRPI 2.0 but not by clinical scores.

Requested Studies:

A Randomized, Double-Blind, Placebo-Controlled Multiple Dose Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Progressive Supranuclear Palsy
Sponsor: AbbVie
Study ID: NCT02985879
Sponsor ID: M15-562