Genetics in medicine : official journal of the American College of Medical Genetics · 2018
Efficacy, safety profile, and immunogenicity of alglucosidase alfa produced at the 4,000-liter scale in US children and adolescents with Pompe disease: ADVANCE, a phase IV, open-label, prospective study.
Клиническое исследование IV фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Hahn Si Houn, Kronn David, Leslie Nancy D, Pena Loren D M, Tanpaiboon Pranoot, Gambello Michael J, Gibson James B, Hillman Richard, Stockton David W, Day John W, Wang Raymond Y, An Haack Kristina, Shafi Raheel, Sparks Susan, Zhao Yang, Wilson Catherine, Kishnani Priya S, Pompe ADVANCE Study Consortium
Аннотация
PURPOSE: Pompe disease results from lysosomal acid α-glucosidase (GAA) deficiency and its associated glycogen accumulation and muscle damage. Alglucosidase alfa (recombinant human GAA (rhGAA)) received approval in 2006 as a treatment for Pompe disease at the 160 L production scale. In 2010, larger-scale rhGAA was approved for patients up to 8 years old without cardiomyopathy. NCT01526785 evaluated 4,000 L rhGAA efficacy/safety in US infantile- or late-onset Pompe disease (IOPD, LOPD) patients up to 1 year old transitioned from 160 L rhGAA.
METHODS: A total of 113 patients (87 with IOPD; 26 with LOPD) received 4,000 L rhGAA for 52 weeks dosed the same as previous 160 L rhGAA. Efficacy was calculated as the percentage of patients stable/improved at week 52 (without death, new requirement for invasive ventilation, left ventricular mass z-score increase >1 if baseline was >2, upright forced vital capacity decrease ≥15% predicted, or Gross Motor Function Measure-88 decrease ≥8 percentage points). Safety evaluation included an extension ≤20 months.
RESULTS: Week 52 data was available for 104 patients, 100 of whom entered the extension. At week 52, 87/104 (83.7%) were stable/improved. Overall survival was 98.1% overall, 97.6% IOPD, 100% LOPD; 92.4% remained invasive ventilator-free (93.4% IOPD, 88.7% LOPD). Thirty-five patients had infusion-associated reactions. Eight IOPD patients died of drug-unrelated causes.
CONCLUSIONS: Most Pompe disease patients were clinically stable/improved after transitioning to 4,000 L rhGAA. Safety profiles of both rhGAA forms were consistent.
METHODS: A total of 113 patients (87 with IOPD; 26 with LOPD) received 4,000 L rhGAA for 52 weeks dosed the same as previous 160 L rhGAA. Efficacy was calculated as the percentage of patients stable/improved at week 52 (without death, new requirement for invasive ventilation, left ventricular mass z-score increase >1 if baseline was >2, upright forced vital capacity decrease ≥15% predicted, or Gross Motor Function Measure-88 decrease ≥8 percentage points). Safety evaluation included an extension ≤20 months.
RESULTS: Week 52 data was available for 104 patients, 100 of whom entered the extension. At week 52, 87/104 (83.7%) were stable/improved. Overall survival was 98.1% overall, 97.6% IOPD, 100% LOPD; 92.4% remained invasive ventilator-free (93.4% IOPD, 88.7% LOPD). Thirty-five patients had infusion-associated reactions. Eight IOPD patients died of drug-unrelated causes.
CONCLUSIONS: Most Pompe disease patients were clinically stable/improved after transitioning to 4,000 L rhGAA. Safety profiles of both rhGAA forms were consistent.