Table 2.
Summary of seven uncontrolled extensions with external controls
Study # / NCT number | Title of extension trial (clinicaltrials.gov) | Condition | Active ingredient | Duration of extension trial | Treatment arms for extension | Treatment of External control | Data source for external control | Outcomes assessed in external control analysis (effectiveness/safety) |
---|---|---|---|---|---|---|---|---|
# 1 / 01931839 | A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis | Cystic fibrosis |
Lumacaftor/ ivacaftor combination therapy |
96 weeks |
Two dosing strategies: lumacaftor 400–600 mg/ivacaftor 250 mg |
Unspecified | Cystic Fibrosis Foundation Patient Registry |
Change in predicted forced expiratory volume; weight; BMI (effectiveness) |
# 2 / 01415427 | Long‐Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) |
Morquio A (mucopolysaccharidosis IVA) |
Elosulfase alfa | 96 weeks |
Two dosing strategies: 2 mg/kg/week; 2 mg/kg/every other week with transition to 2 mg/kg/week between week 36 and week 96 |
Untreated | Morquio A natural history study; MOR‐001; NCT00787995 |
Various physical function / ADL assessments; urine keratan sulfate levels; forced vital capacity; forced expiratory volume; maximum voluntary ventilation (effectiveness) |
# 3 / 01540409 | Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy | Duchenne muscular dystrophy | Eteplirsen (AVI‐4658) | 156 weeks |
Two dosing strategies: 30–50 mg/kg/week |
Untreated | Baseline samples from untreated control arm from separate phase III eteplirsen study (PROMOVI) | Dystrophin expression (Means of PDPF, Bioquant relative fluorescence intensity, and Western blot) (effectiveness) |
2 natural history cohorts from the Leuven Neuromuscular Reference Center (LNMRC) and the Italian Telethon registry |
6‐Minute Walk Test; pulmonary function (effectiveness) |
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# 4 / 01214421 | Open‐Label Tolvaptan Study in Subjects with ADPKD (TEMPO 4/4) | autosomal dominant polycystic kidney disease | Tolvaptan | 2 year | Tolvaptan | Unspecified | CRISP cohort (NCT01039987) and the HALT PKD Study B clinical trial (NCT01885559) | eGFR (effectiveness) |
# 5 (unpublished)/02760277 | An Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy | Duchenne muscular dystrophy | Vamorolone | 24 weeks | Four dosing strategies from 0.25 to 6.0 mg/day/day |
(1) untreated (2) prednisone |
unspecified prior studies |
|
# 6 (unpublished)/03167255 | Extension Study of NS‐065/NCNP‐01 in Boys With Duchenne Muscular Dystrophy | Duchenne muscular dystrophy | NS‐065/NCNP‐01 | 168 weeks |
Two dosing strategies: 40 and 80 mg/kg |
N/S (matched historical controls) | N/S | Various physical function (e.g., walking) assessments; muscle strength (effectiveness) |
# 7 (unpublished)/03759379 | HELIOS‐A: A Study of Vutrisiran (ALN‐TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis | Hereditary transthyretin amyloidosis | Vutrisiran (ALN‐TTRSC02) | N/S | Vutrisiran | Placebo | prior clinical trial (APOLLO study) | N/S |
ADL, activity of daily living; BMI, body mass index; eGFR, estimated glomerular filtration rate; N/S, not specified; PDPF, percentage of dystrophin positive fibers.