Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naive and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study
| العنوان: | Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naive and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study |
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| المؤلفون: | Philip Van Damme, Pascal Laforêt, Benedikt Schoser, Barry J. Byrne, Loren D.M. Pena, Richard J. Barohn, Ozlem Goker-Alpan, Kerry Culm-Merdek, Ans T. van der Ploeg, Volker Straub, Karl Eugen Mengel, Beth L. Thurberg, Jean Pouget, Raheel Shafi, Katherine Kacena, Alan Pestronk, Peter Young, John Vissing, Shafeeq Ladha, Claude Desnuelle, Jaya Trivedi |
| المساهمون: | Pediatrics |
| المصدر: | Neuromuscular Disorders, 29(3), 167-186. Elsevier Ltd. NEO1 Investigator Group 2019, ' Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease : A phase 1, open-label, multicenter, multinational, ascending dose study ', Neuromuscular Disorders, vol. 29, no. 3, pp. 167-186 . https://doi.org/10.1016/j.nmd.2018.12.004Test |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Avalglucosidase alfa (neoGAA), 0301 basic medicine, Male, GLUCOSE TETRASACCHARIDE, Lysosomal acid alpha-glucosidase (GAA) deficiency, CHILDREN, Pulmonary function testing, MOTOR FUNCTION, 0302 clinical medicine, Medicine, Genetics (clinical), Late-onset Pompe disease (LOPD), Glycogen Storage Disease Type II, Alglucosidase alfa, MOUSE MODEL, Enzyme replacement therapy, Middle Aged, Treatment Outcome, Neurology, Tolerability, SKELETAL-MUSCLE, Female, Life Sciences & Biomedicine, MUSCLE TRAINING RMT, Glycogen, 6-MINUTE WALK, medicine.drug, Adult, medicine.medical_specialty, Clinical Neurology, GLYCOGEN, 03 medical and health sciences, FEV1/FVC ratio, Pharmacokinetics, Internal medicine, Humans, Enzyme Replacement Therapy, Adverse effect, Science & Technology, business.industry, Neurosciences, alpha-Glucosidases, ADULTS, Glycogen storage disease type II, SEVERITY, 030104 developmental biology, Pharmacodynamics, Pediatrics, Perinatology and Child Health, Neurosciences & Neurology, Neurology (clinical), Glucan 1,4-alpha-Glucosidase, business, 030217 neurology & neurosurgery |
| الوصف: | This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). One Naïve patient withdrew for study drug-related SAEs (respiratory distress/chest discomfort). Infusion-associated reactions (IARs) affected 8 patients. Most treatment-emergent AEs/IARs were non-serious with mild-to-moderate intensity. At screening, 5 Switch patients tested positive for anti-avalglucosidase alfa antibodies; on-treatment, 2 Switch and 9 Naïve patients seroconverted. Post-infusion, avalglucosidase alfa plasma concentrations declined monoexponentially (t1/2z∼1.0 h). AUC was 5-6 × higher in the 20 vs 5 mg/kg group. Pharmacokinetics were similar between Switch and Naïve groups and over time. Baseline quadriceps muscle glycogen was low (∼6%) in most patients, generally remaining unchanged thereafter. Exploratory efficacy parameters (pulmonary function/functional capacity) generally remained stable or improved. Avalglucosidase alfa's well-tolerated safety profile and exploratory efficacy results support further avalglucosidase alfa development. ispartof: NEUROMUSCULAR DISORDERS vol:29 issue:3 pages:167-186 ispartof: location:England status: published |
| وصف الملف: | Print-Electronic; application/pdf |
| تدمد: | 0960-8966 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf2f385d766335b6e27ce068b0b3a3b8Test https://doi.org/10.1016/j.nmd.2018.12.004Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cf2f385d766335b6e27ce068b0b3a3b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09608966 |
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