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Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study |
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| Authors: | Christian J. Hendriksz Barbara Burton Thomas R. Fleming Paul Harmatz Derralynn Hughes Simon A. Jones Shuan-Pei Lin Eugen Mengel Maurizio Scarpa Vassili Valayannopoulos Roberto Giugliani Peter Slasor Debra Lounsbury Wolfgang Dummer STRIVE Investigators |
| Affiliation: | 1. Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK 13. Manchester Academic Health Science Centre, The Mark Holland Metabolic Unit, Salford Royal Foundation NHS Trust, Ladywell NW2- 2nd Floor Room 107, Salford, Manchester, M6 8HD, UK 2. Ann and Robert H. Lurie Children’s Hospital and Northwestern University Feinberg School of Medicine, Chicago, IL, USA 3. Department of Biostatistics, University of Washington, Seattle, WA, USA 4. Children’s Hospital and Research Center Oakland, Oakland, CA, USA 5. Royal Free and University College Medical School, London, UK 6. Manchester Centre for Genomic Medicine, St Mary’s Hospital, CMFT, MAHSC, University of Manchester, Manchester, UK 7. Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan 8. Villa Metabolica, Centre for Pediatric and Adolescent Medicine, MC University of Mainz, Mainz, Germany 9. Department of Pediatrics, University of Padova, Padova, Italy 10. H?pital Necker-Enfants Malades and IMAGINE Institute, Paris, France 11. Medical Genetics Service/HCPA, Department of Genetics/UFRGS and INAGEMP, Porto Alegre, Brazil 12. BioMarin Pharmaceutical Inc., Novato, CA, USA |
| Abstract: | ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5 years (N?=?176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P?=?0.017) for weekly and 0.5 m (95 % CI ?17.8, 18.9; P?=?0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI ?2.1, 4.4; P?=?0.494) for weekly and ?0.5 stairs/min (95 % CI ?3.7, 2.8; P?=?0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile. |
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