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

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.

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

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

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 P.076 Safety of Eteplirsen, a phosphorodiamidate morpholino oligomer, in Duchenne Muscular Dystrophy patients amenable to Exon 51 skipping

2018 ◽  
Vol 45 (s2) ◽  
pp. S36-S36
Author(s):  
J Mah ◽  
J Lynch ◽  
C Campbell
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Nasal Congestion ◽  
Functional Decline ◽  
Transient Temperature ◽  
Upper Respiratory Tract ◽  
Facial Flushing ◽  
Reading Frame ◽  
Upper Respiratory

Background: Duchenne muscular dystrophy (DMD) is an X-linked disorder affecting 1:3500-5000 live male births, causing a life-limiting form of muscular dystrophy. Whole exon deletions disrupting the reading frame result in near-absence of sarcolemmal dystrophin, essential for muscle function. Eteplirsen is a phosphorodiamidate morpholino oligomer (PMO) designed to induce production of internally-truncated dystrophin in certain patients. Methods: As of June 2016, 150 patients (4-19 years of age) with DMD received eteplirsen in 7 clinical trials. 143 patients received ≥1 intravenous infusion of eteplirsen (range: 0.5 - 50 mg/kg). 81 (54%) received treatment for ≥1 year (Range: 1-4+ years). Results: Common (>15%) adverse events (AEs) were cough, headache, vomiting, back pain, extremity pain, contusion, nasopharyngitis, upper respiratory tract infection, nasal congestion, arthralgia and rash. Non-serious facial flushing, erythema and mild transient temperature elevation occurred with eteplirsen. 10 (6.7%) patients experienced severe AEs; 12 (8%) patients experienced serious AEs. All serious and all but 1 severe AEs were considered unrelated to eteplirsen by the treating physicians. Serial echocardiograms in 12 treated patients demonstrated no functional decline over 4+ years. Conclusions: Eteplirsen’s tolerability will continue to be assessed in ongoing clinical trials.An updated data summary will be presented.

Jumping Mechanography is a Suitable Complementary Method to Assess Motor Function in Ambulatory Boys with Duchenne Muscular Dystrophy

2021 ◽  
Author(s):  
Astrid Blaschek ◽  
Martin Rodrigues ◽  
Rainer Rawer ◽  
Christine Müller ◽  
Lena Ille ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Reaction Force ◽  
Drug Efficacy ◽  
Measuring Method ◽  
Physical Parameters ◽  
First Choice ◽  
Standing Up ◽  
Jumping Mechanography

Abstract Objective The number of clinical trials for Duchenne muscular dystrophy (DMD) has increased substantially lately, therefore appropriate clinical instruments are needed to measure disease progression and drug efficacy. Jumping mechanography is a medical diagnostic method for motion analysis, which allows to quantify physical parameters. In this study, we compared mechanography with timed function tests (TFTs). Methods 41 ambulatory DMD patients performed a total of 95 chair rising tests (CRT) and a total of 76 single two-legged jumps (S2LJ) on a mechanography ground reaction force platform. The results were correlated with a 6-minute walk test (6MWT) and the time required to run 10 meters, stand up from a supine position, and climb four stairs, all performed in the same setting. Results Our measurements show a high correlation between mechanography and the TFTs: S2LJ/10-m run, r = 0.62; CRT/10-m run, r = 0.61; S2LJ/standing up from supine, r = 0.48; CRT/standing up from supine, r = 0.58; S2LJ/climb four stairs, r = 0.55; CRT/climb four stairs, r = 0.51. The correlation between mechanography and the 6MWT was only moderate with r = 0.38 for S2LJ/6MWT and r = 0.39 for CRT/6MWT. Interpretation Jumping mechanography is a reliable additional method, which can be used for physical endpoint measurements in clinical trials. We confirmed our assumption, that the method provides additional information concerning performance at movement with higher power output. We suggest using the S2LJ as a first-choice tandem tool combined with the 6MWT. In patients with higher disability, the CRT is an alternative measuring method, because with the progression of the disease this is longer feasible.

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