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Activity Number: 476 - SPEED: Clinical Trial Design, Longitudinal Analysis, and Other Topics in Biopharmaceutical Statistics
Type: Contributed
Date/Time: Wednesday, August 1, 2018 : 8:30 AM to 10:20 AM
Sponsor: Biopharmaceutical Section
Abstract #329832 Presentation
Title: A Novel Blind Start Study Design to Investigate Vestronidase Alfa for Mucopolysaccharidosis VII, an Ultra-Rare Genetic Disease
Author(s): Wenjie Song* and Chao-Yin Chen and Christine Haller and Emil Kakkis
Companies: Ultragenyx Pharmaceutical Inc and Ultragenyx Pharmaceutical Inc and Ultragenyx Pharmaceutical Inc and Ultragenyx Pharmaceutical Inc
Keywords: Study Design; Rare Disease; Blind Start; MDRI; MID

Drug development in ultra-rare diseases is challenging because small sample sizes and heterogeneity hamper the ability of randomized, placebo-controlled trials with a single primary endpoint to demonstrate treatment effects. To overcome these challenges, a novel randomized Blind Start design was used in a Phase 3 study of vestronidase alfa in mucopolysaccharidosis VII, an ultra-rare lysosomal disease with heterogeneous presentation and severity spectrum. 12 subjects were randomized to 1 of 4 blinded groups, each crossing over to active treatment in a blinded fashion at different timepoints. To capture improvement in subject-specific domains, a Multi-Domain Responder Index (MDRI) was used, summing the minimal important difference scores from 6 domains (6-minute walk test, forced vital capacity, shoulder flexion, visual acuity, and Bruininks-Oseretsky test of fine motor and gross motor proficiency). MDRI showed overall improvement (mean[SD]=0.5 [0.8]). The Blind Start and MDRI design improve statistical power enhancing detection of a treatment effect in this rare disease, while maintaining objectivity and eliminating potential bias by incorporating a variable blinded placebo period.

Authors who are presenting talks have a * after their name.

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