Table 1 Characteristics of included studies
From: Exon skipping for Duchenne muscular dystrophy: a systematic review and meta-analysis
Study ID (Study Period) Funding source | Number radomized, countries | Mean age of participants y (SD, range) | Mean FVC at baseline (SD) | Mean 6MWT at baseline meters (SD) | Interventions (n) | Co-intervention with glucocorticoids | Treatment duration | Observation period | Outcome assessed |
|---|---|---|---|---|---|---|---|---|---|
Flanigan 2014 [24] (2010–2011) GlaxoSmithKline | 20 France USA | 12.7 (1.4, 9–16) | NA | NA | Drisapersen, single SC injection 1. 3 mg/kg/dose (6) 2. 6 mg/kg/dose (6) 3. 9 mg/kg/dose (3) 4. Placebo (5) | By trial arm, n (%) 1. 3 mg/kg/dose: 3 (50) 2. 6 mg/kg/dose: 5 (83) 3. 9 mg/kg/dose: 2 (67) 4. Placebo: 3 (60) | Single dose | 5 mo | AE* PK Safety and tolerability |
Voit 2014 [20] (2010–2012) GlaxoSmithKline, Prosensa Terapeutics BV | 53 Belgium France Germany Netherlands Spain Turkey Australia Israel United Kingdom | 7.3 (1.5, 5–11) | FVC litres (SD) n = 51 1.38 (0.50) | n = 53 408.72 (61.61) | Drisapersen 6 mg/kg/time SC Twice/wk. for 3 w followed by below schedule: 1. Continuous (once/wk) (18) 2. Intermittent (twice/wk. at 1,3,5 wk. and once/w at 2,4,6 wk. No drug during 7–10 wk., then the 10-wk cycle was repeated. (17) 3. Placebo (mannitol) (18) | By trial arm, n (%) 1. Continuous: continuous GC 12 (67), intermittent GC 6 (33) 2. Intermittent: continuous GC 9 (53), intermittent GC 8 (47) 3. Placebo: continuous GC 11 (61), intermittent GC 7 (39) Length of GC use prior to the drug, mean mo (SD) 1. Continuous: 26.0 (21.2) 2. Intermittent: 32.6 (17.0) 3. Placebo: 24.2 (14.0) | 48 wk | 4wk after the last dose | 6MWT at 25 wk * 6MWT at 49 wk.** NSAA at 25 wk.* NSAA at 49 wk. AE* Timed test** PedsQL at 25 wk., 49 wk.** Safety and tolerability Myometry Dystrophin level in muscle Production of exon skipped mRNA in muscle biopsy Serum CK Respiratory function Cardiac function Frequency of falls during 6MWT Time to loss of ambulation PK |
NCT01254019 [22] (2010–2013) GlaxoSmithKline | 186 Argentina Belgium Brazil Canada Chile Czech Republic Denmark France Germany Italy Japan Korea Netherlands Norway Poland Russian Federation Spain Taiwan Turkey | 8.2 (2.4) | FVC-% of predicted n = 183 87.25 (28.61) | n = 186 340.92 (94.49) | Drisapersen, once/wk., SC 1. 6 mg/kg/dose (125) 2. Placebo (61) | NA | 48 wk | 20wk after the last dose | 6MWT at 48wk ** 6MWT at 24wk* Timed test** AE* PedsQL at 48 wk.** NSAA at 48wk Myometry Frequency of falls during 6MWT Time to loss of ambulation Serum CK Respiratory function Cardiac function Production of exon skipped mRNA in muscle biopsy PK CGI-I scale HUI score |
Mendell 2013 [23] (2011–2012) Sarepta Therapeutics, Muscular Dystrophy Association, Parent Project Muscular Dystrophy, NCRR/NIH, NIH Roadmap for Medical Research | 12 USA | 8.8 (1.3, 7–10) | NA | n = 12 381.93 (51.91) | Eteplirsen, once/wk., IV 1.30 mg/kg/dose (4) 2.50 mg/kg/dose (4) 3.Placebo(PBS) (4) | Usage, n (%) 18-25 mg/d deflazacort 8 (67), 20 mg/d prednisone 1 (8), 25 mg/d prednisone 2 (17), prednisone weekend only 1 (8) | 24 wk | Followed by open-label extension study | %Dystrophin positive fibers 6MWT at 24wk* 6MWT at 12 wk. AE* Timed test** QOL** NSAA at 12 wk. NSAA at 24 wk.* Quantitative muscle testing |
NCT01462292 [21] (2011–2013) GlaxoSmithKline | 51 USA | 7.8 (2.2) | FVC-% of predicted n = 48 98.6 (14.14) | n = 51 408.87 (58.66) | Drisapersen, once/wk., SC 1.3 mg/kg/dose (17) 2.6 mg/kg/dose (18) 3.Placebo (16) | NA | 24 wk | 24 wk. after the last dose | 6MWT at 24 wk * Timed test** NSAA at 24 wk.* AE* Frequency of falls during 6MWT Serum CK Respiratory function Myometry CGI-I Dystrophin expression in muscle PK |