The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis

Abstract

Background: Alpha-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.

Results: 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.

Conclusion: 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.

Keywords: Alpha-mannosidosis; Enzyme-replacement therapy; Patient registry; Recombinant alpha-mannosidase; Velmanase alfa.

Fig. 1

Study design. VA velmanase alfa. ^aIf applicable in accordance with routine clinical practice, unscheduled follow-up visits can be performed at, but not limited to, 3 months after VA treatment start, or whenever deemed appropriate according to clinician judgment for patients who start VA treatment within 1 year prior to registry inclusion. ^bIf a patient is transferred to another continuing care site during the 15-year observational period, the new treating site will be formally involved in the registry following a request of authorization submitted to the relevant ethics committee and regulatory authority to complete the 15-year observational period. ^cPatients can start VA treatment at any time during the course of their participation in the registry; if applicable in accordance with routine clinical practice, the baseline visit should be repeated before administration of VA and unscheduled visits recommended as reported in the schema above