Bayesian adaptive design for clinical trials in Duchenne muscular dystrophy

2021 ◽  
Author(s):  
Stephen L. Lake ◽  
Melanie A. Quintana ◽  
Kristine Broglio ◽  
Jennifer Panagoulias ◽  
Scott M. Berry ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Adaptive Design ◽  
Bayesian Adaptive Design

scholarly journals Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shu Zhang ◽  
◽  
Dongdong Qin ◽  
Liwen Wu ◽  
Man Li ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Hazard Ratio ◽  
Large Cohort ◽  
Muscle Disease ◽  
Clinical Progression ◽  
Large Deletions ◽  
The Mean ◽  
Lower Hazard

Abstract Background Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease in human. We aimed to describe the genotype distribution in a large cohort of Chinese DMD patients and their delayed loss of ambulation by glucocorticoid (GC) treatments. This is to facilitate protocol designs and outcome measures for the emerging DMD clinical trials. Results A total of 1163 patients with DMD were recruited and genotyped. Genotype variations were categorized as large deletions, large duplications, and small mutations. Large deletions were further analyzed for those amenable to exon-skipping therapies. Participants aged 5 years or older were grouped into GC-treated and GC-naïve groups. Clinical progression among different genotypes and their responses to GC treatments were measured by age at loss of ambulation (LOA). Among the mutation genotypes, large deletions, large duplications, and small mutations accounted for 68.79%, 7.14%, and 24.07%, respectively. The mean age at diagnosis was 4.59 years; the median ages at LOA for the GC-naïve, prednisone/prednisolone-treated, and deflazacort-treated groups were 10.23, 12.02, and 13.95 years, respectively. The “deletion amenable to skipping exon 44” subgroup and the nonsense-mutation subgroup had older ages at LOA than the “other deletions” subgroup. Subgroups were further analyzed by both genotypes and GC status. All genotypes showed significant beneficial responses to GC treatment. Deletions amenable to skipping exon 44 showed a lower hazard ratio (0.155). The mean age at death was 18.57 years in this DMD group. Conclusion Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes.

Clinical Trials Using Antisense Oligonucleotides in Duchenne Muscular Dystrophy

2013 ◽  
Vol 24 (5) ◽  
pp. 479-488 ◽  
Author(s):  
Taeyoung Koo ◽  
Matthew J. Wood
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotides

P.13.14 Future clinical and biomarker development for SMTC1100, the first utrophin modulator to enter clinical trials for Duchenne Muscular Dystrophy (DMD)

2013 ◽  
Vol 23 (9-10) ◽  
pp. 813 ◽  
Author(s):  
J.M. Tinsley ◽  
N. Robinson ◽  
F.X. Wilson ◽  
G. Horne ◽  
R.J. Fairclough ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy

Development of novel observer-reported outcome assessments in clinical trials of patients with Duchenne muscular dystrophy

2017 ◽  
Vol 27 ◽  
pp. S233 ◽  
Author(s):  
D. Martin ◽  
C. Macary ◽  
C. Jones ◽  
L. Walker ◽  
M. O'Connor ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Outcome Assessments

P16 Towards a consensus on biochemical outcome measures for Duchenne muscular dystrophy clinical trials

2014 ◽  
Vol 24 ◽  
pp. S11
Author(s):  
S. Torelli ◽  
K. Anthony ◽  
V. Arechavala-Gomeza ◽  
L.E. Taylor ◽  
A. Vulin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Outcome Measures

scholarly journals Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: Implication for clinical trials

2010 ◽  
Vol 20 (5) ◽  
pp. 295-301 ◽  
Author(s):  
Virginia Arechavala-Gomeza ◽  
Maria Kinali ◽  
Lucy Feng ◽  
Michela Guglieri ◽  
Geraldine Edge ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy

scholarly journals A Bayesian adaptive design for clinical trials in rare diseases

2017 ◽  
Vol 113 ◽  
pp. 136-153 ◽  
Author(s):  
S. Faye Williamson ◽  
Peter Jacko ◽  
Sofía S. Villar ◽  
Thomas Jaki
Keyword(s):  
Clinical Trials ◽  
Rare Diseases ◽  
Adaptive Design ◽  
Bayesian Adaptive Design

P07 Translation related clinical trials in duchenne muscular dystrophy (DMD) in the UK

2010 ◽  
Vol 20 ◽  
pp. S6-S7
Author(s):  
R. Choudhury ◽  
G. Barreto ◽  
K. Ganeshaguru ◽  
S. Cirak ◽  
M. Scoto ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
The Uk

scholarly journals New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trials

2007 ◽  
Vol 13 (12) ◽  
pp. 520-526 ◽  
Author(s):  
Giulio Cossu ◽  
Maurilio Sampaolesi
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
New Therapies
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