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. 2021 Aug 10;111(1):187–199. doi: 10.1002/cpt.2346

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)
# 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# 5 (unpublished)/02760277 An Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy Duchenne muscular dystrophy Vamorolone 24 weeks Four dosing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

  1. muscle function (effectiveness)

  2. biomarkers (safety)
# 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.