Background
Congenital Myotonic Dystrophy Type 1 (CDM1) is a rare, genetic disorder. There are no gold-standard clinician rating scales for CDM1.
Objectives
To create a fit-for-purpose outcome measure for assessing efficacy in registration clinical trials, utilizing best practices in rare disease scale development.
Approach
A CDM1-specific, clinician-completed, rating scale was designed, utilizing Natural History studies, therapeutic area expert advice, and FDA feedback. An initial 17-item version assessed features such as impaired muscle functioning, fatigue, myotonia, gastrointestinal and cognitive problems. The scale, and a robust rater training curriculum, were piloted in a Phase 2 congenital/childhood-onset DM1 study (NCT02858908). Following FDA feedback, the 17 items were reduced to 11 with each item rated via a 5-point Likert severity scale (CDM1-RS).
Results
The 11-item CDM1-RS is the primary efficacy measure in an ongoing Phase 2/3 clinical trial in pediatric CDM1 (NCT03692312), co-administered with the Clinical Global Impression rating scales which allow for identification of clinically important differences on the CDM1-RS. To date (n=31), most commonly endorsed items at Baseline on the CDM1-RS are difficulty thinking (mean pre-treatment score = 2.4, using a 0 to 4 Likert scale), communication difficulties (2.3), and problems with hands or arms (2.07), while the least endorsed items are signs of pain (0.31), breathing difficulties (0.82), and choking or swallowing issues (0.93).
Conclusions
The CDM1-RS is a low-burden tool with sound psychometric properties. It provides clinicians with a composite approach to efficiently assess the phenotypic heterogeneity common in CDM1 youth. The CDM1-RS may improve the quality of clinical care as well as clinical trials in this orphan population.