Longitudinal Data Collection in Pediatric and Adult Patients With Spinal Muscular Atrophy in Latin America

Protocol-LATAM RegistrAME: Longitudinal Data Collection in Pediatric and Adult Patients With Spinal Muscular Atrophy in Latin America - a Regional Registry

The natural history of SMA patients has changed, due to the improvements in treatment and technological advances. The systematic collection of data from routine clinical practice in multiple Latin American countries, harmonized to an internationally aligned core data set, is important to advancing the understanding the natural history of disease in the region and the influence of different drug treatments on patient outcomes. These data are critical to improving the care of these patients. So far, clinical trials regarding therapeutic approaches for SMA patients only cover a subgroup of the broad spectrum of severity of SMA. Thus, there is a strong need to monitor the full range of treated and untreated SMA patients in a real-world context.The aim of this study is to set up a regional healthcare provider (HCP) entered registry. The planned SMA registry will provide an online platform to collect longitudinal data on SMA patients across Latin America to achieve a better understanding of the clinical characteristics of SMA patients, the natural history of the disease, the use of DMTs and patients' outcomes, as well as to support further research projects and regional data generation.

This is a retrospective and prospective, multicenter non-randomized registry in Latin America. The variables included in the RegistrAME registry are based on the core items defined by the TREAT-NMD for SMA registries and the RegistrAME steering committee consensus. Items such as demographic characteristics, date of genetic test result, clinical diagnosis, functional status and pulmonary function, among others, are included in RegistrAME. The RegistrAME registry will allow the inclusion of retrospective clinical data in those centers where natural history studies of for spinal muscular atrophy are currently being conducted. RegistrAME will also offer a standardized structure for prospective data collection in all centers. The current aim of this registry is to include centres in LATAM meeting the structural and personnel requirements for performing the planned regular registry-related investigations. These reference centers in LATAM (Latin America) will be selected from COEs which 1) have the potential to enroll and make the proper patient follow up, 2) have experience in treating SMA, and 3) have experience in conducting clinical trials. An electronic Case Report Form (e-CRF) will be created by the ARO (Academic Research Organization) from Hospital Albert Einstein, using REDCap (Research Electronic Data Capture). The electronic Case Report Form (e-CRF) created to meet international standards for data protection and quality management, and to harmonize the platform with those currently used by other countries. No interventions will be performed in this study, the RegistrAME is observational study non-randomized, international multicenter study (Registration of patients in Latin America). Data collection aims to gather as much information as possible regarding the clinical profile of patients, interventions performed in the routine of care and clinical evolution over time (Real World Evidence-RWE). After confirmation of eligibility and informed consent, patients will undergo medical evaluation, and then retrospective data collection (when possible and limited to 6 months before the patient inclusion in the study), baseline data and continuation of longitudinal data collection will be started. Data entry is planned to be performed every carried out at intervals of 4 to 6 months (according to the type of SMA), depending on the regular healthcare planning of each clinical site. The study will assess disease progression, both the natural history of the disease and the effectiveness of different SMA specific drug treatments on patient outcomes. Duration of disease, survival with or without ventilatory support, motor function, pulmonary function, developmental milestones achieved, growth parameters, orthopedic symptoms, functional assessments (CHOP-INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders), HINE-2 (Hammersmith Infant Neuromuscular Examination - session 2), HFMSE (Hammersmith Motor Functional Scale Expanded), RULM (Revised Upper Limb Module), and 6MWT (The six minute walking test)) will be analyzed depending on the functional capacity of the patients and 5q SMA type over time.

Inclusion Criteria:

• Genetically confirmed 5q SMA patients at all ages;
• Consent to participate in the study, expressed by the patient or responsible or legal guardian of the pediatric patient/ responsible or legal guardian of the patient with cognitive impairment of understanding the registration protocol.

Exclusion Criteria:

• Patients without a genetic diagnosis confirming SMA 5q;
• Other types of SMA (non 5q SMA);
• Patients who do not accept to participate in the observational study;
• Patients without the legal capacity who are unable to understand the nature, significance and consequences of participating in the registry, or, in such cases, without a legal or responsible guardian.