Lead Investigator: James Signorovitch, Analysis Group
Title of Proposal Research: Development of natural history controls to contextualize clinical trial outcomes of boys with Duchenne muscular dystrophy treated with DS-5141B
Vivli Data Request: 7072
Funding Source: Funded by Daiichi Sankyo Co. Ltd. Analysis Group Inc. has been contracted by Daiichi Sankyo Co. Ltd to conduct this research.
Potential Conflicts of Interest: Members of the research team are employees of Daiichi Sankyo Co. Ltd. or Analysis Group. Analysis Group will receive payment from Daiichi Sankyo Co. Ltd for consulting services on this project. Analysis Group will be the only party with access to the data and analyses will be conducted according to a pre-specified analysis plan as submitted in this application.
Summary of the Proposed Research:
Duchenne muscular dystrophy (DMD) is a rare, X-linked, progressive neuromuscular disorder arising from mutations to the DMD gene that result in nonfunctional dystrophin protein. Globally, DMD affects approximately one in every 3,500 newborn males. Initial manifestations of the disorder include progressive declines in motor function during childhood that typically culminate in complete loss of independent walking ability by adolescence. Additional impacts include worsening heart and lung function, as well as a deterioration in bone health; over time, these disabling declines collectively contribute to mortality by early adulthood. The median survival for boys with DMD is 21.8 years.
Deletions of exons in the dystrophin gene are the most common type of mutation. Antisense oligonucleotide (AON)-mediated exon skipping is a therapeutic approach that can potentially restore production of dystrophin protein. DS-5141b is an AON under development by Daiichi Sankyo targeted for use in patients with mutations amenable to exon 45 skipping. The safety, tolerability, efficacy, and pharmacokinetic (PK) profile of DS-5141b in patients with DMD amenable to exon 45 skipping is being investigated in a phase 1/2 study (Study J101).
In the absence of an untreated control group in Study J101, external data from comparable patients is needed to help contextualize clinical outcomes of patients treated with DS-5141b.
This study will use data from the PRO-DMD-01 natural history study as the primary data source for external controls. The PRO-DMD-01 study (NCT01753804) was a prospective observational study of disease progression in boys with DMD. The study included patients from 16 centers in the United States, Argentina, Belgium, Brazil, France, Germany, Italy, Netherlands, Sweden, and Turkey. Study assessments occurred every 6 months. The dataset provides longitudinal, patient-level data for 269 boys with DMD. Data are also available on demographics, steroid use, and several measures of motor, lung, and heart function. Additional external control data for this study will also be available via the collaborative Trajectory Analysis Project (cTAP), a consortium of academic, industry and patient advocacy stakeholders and data scientists established to solve critical problems in drug development in DMD.
A Prospective Natural History Study of Progression of Physical Impairment, Activity Limitation and Quality of Life in Duchenne Muscular Dystrophy.
Data Contributor: Cure Duchenne
Study ID: NCT01753804
Sponsor ID: PRO-DMD-01