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An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy.

Publication ,  Journal Article
Goker-Alpan, O; Longo, N; McDonald, M; Shankar, SP; Schiffmann, R; Chang, P; Shen, Y; Pano, A
Published in: Drug Des Devel Ther
2016

BACKGROUND: Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. METHODS: In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. RESULTS: Among five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=-0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (-3.3, 3.7) g/m(2.7); midwall fractional shortening, -0.62% (-2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (-11.4, 11.7) mL/min/1.73 m(2); urine protein, -1.8 (-6.0, 2.4) mg/dL; urine microalbumin, 0.6 (-0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), -5.71 (-10.8, -0.6) nmol/mL; urinary Gb3, -1,403.3 (-3,714.0, 907.4) nmol/g creatinine, or clinical quality-of-life outcomes. CONCLUSION: Fifty-five weeks' agalsidase alfa ERT at 0.2 mg/kg every other week was well tolerated. Disease progression may be slowed when ERT is started prior to major organ dysfunction. TRIAL REGISTRATION: https://ClinicalTrials.gov identifier NCT01363492.

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Published In

Drug Des Devel Ther

DOI

EISSN

1177-8881

Publication Date

2016

Volume

10

Start / End Page

1771 / 1781

Location

New Zealand

Related Subject Headings

  • alpha-Galactosidase
  • Recombinant Proteins
  • Male
  • Isoenzymes
  • Humans
  • Female
  • Fabry Disease
  • Enzyme Replacement Therapy
  • Child
  • Adolescent
 

Citation

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Goker-Alpan, O., Longo, N., McDonald, M., Shankar, S. P., Schiffmann, R., Chang, P., … Pano, A. (2016). An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy. Drug Des Devel Ther, 10, 1771–1781. https://doi.org/10.2147/DDDT.S102761
Goker-Alpan, Ozlem, Nicola Longo, Marie McDonald, Suma P. Shankar, Raphael Schiffmann, Peter Chang, Yinghua Shen, and Arian Pano. “An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy.Drug Des Devel Ther 10 (2016): 1771–81. https://doi.org/10.2147/DDDT.S102761.
Goker-Alpan O, Longo N, McDonald M, Shankar SP, Schiffmann R, Chang P, et al. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy. Drug Des Devel Ther. 2016;10:1771–81.
Goker-Alpan, Ozlem, et al. “An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy.Drug Des Devel Ther, vol. 10, 2016, pp. 1771–81. Pubmed, doi:10.2147/DDDT.S102761.
Goker-Alpan O, Longo N, McDonald M, Shankar SP, Schiffmann R, Chang P, Shen Y, Pano A. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy. Drug Des Devel Ther. 2016;10:1771–1781.

Published In

Drug Des Devel Ther

DOI

EISSN

1177-8881

Publication Date

2016

Volume

10

Start / End Page

1771 / 1781

Location

New Zealand

Related Subject Headings

  • alpha-Galactosidase
  • Recombinant Proteins
  • Male
  • Isoenzymes
  • Humans
  • Female
  • Fabry Disease
  • Enzyme Replacement Therapy
  • Child
  • Adolescent