Hennermann, Julia BGuffon, NathalieCattaneo, FedericaCeravolo, FerdinandoBorgwardt, LineLund, Allan MGil-Campos, MercedesTylki-Szymanska, AnnaMuschol, Nicole M2023-02-092023-02-092020-09-14Hennermann JB, Guffon N, Cattaneo F, Ceravolo F, Borgwardt L, Lund AM, et al. The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis. Orphanet J Rare Dis. 2020 Sep 29;15(1):271.http://hdl.handle.net/10668/16346Alpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. SPARKLE is an alpha-mannosidosis registry intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis. It is a post-approval commitment to European marketing authorization for Velmanase alfa (Lamzede®), the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively. The SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting patient enrollment in 2020. Patients will be followed for up to 15 years. Safety and effectiveness as post-authorization outcomes under routine clinical care in patients with treatment will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned. This study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Alpha-mannosidosisEnzyme-replacement therapyPatient registryRecombinant alpha-mannosidaseVelmanase alfaEnzyme Replacement TherapyHumansMulticenter Studies as TopicProspective StudiesRegistriesalpha-Mannosidasealpha-Mannosidosisresearch article32993743open accessEstudios multicéntricos como asuntoEstudios prospectivosHumanosSistema de registrosTerapia de reemplazo enzimáticoalfa-manosidasaalfa-manosidosis10.1186/s13023-020-01549-81750-1172PMC7525940https://ojrd.biomedcentral.com/track/pdf/10.1186/s13023-020-01549-8https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525940/pdf