A Long-term Safety Study in Brazilian Patients With a Diagnosis of Spinal Muscular Atrophy Treated With Zolgensma (ARISER)

A Long-term Safety Study in Brazilian Patients With a Confirmed Diagnosis of Spinal Muscular Atrophy (SMA) Treated With Onasemnogene Abeparvovec (Zolgensma®) - ARISER Study

A long-term safety study in Brazilian patients with a confirmed diagnosis of Spinal Muscular Atrophy (SMA) treated with Onasemnogene Abeparvovec (Zolgensma®)

Study Overview

• Status: Recruiting
• Conditions: Spinal Muscular Atrophies
• Intervention / Treatment: Other: Onasemnogene Abeparvovec

Detailed Description

This study is a non-interventional Post Authorization Safety Study (PASS) to evaluate long-term, real-world safety data of Brazilian pediatric patients diagnosed with SMA and treated with Onasemnogene Abeparvovec (Zolgensma®) for up to 15 years after the treatment. This study will support the benefit-risk assessment of Onasemnogene Abeparvovec in the approved indications and may also allow for detection of new safety signals and provide further guidance on the management of safety risks associated with Onasemnogene Abeparvovec to patients/caregivers, health care providers (HCPs) and treating physicians, as required by Brazilian Health Authority ANVISA as a conditional measure for granting Zolgensma®'s authorization.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Brazil
  • PR
    • Curitiba, PR, Brazil, 81520-060
      • Recruiting
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of approximately 50 Brazilian pediatric patients with SMA who were treated with Onasemnogene Abeparvovec (Zolgensma®) in the commercial setting, the closed MAP, or the phase IV OFELIA trial. Patients will be recruited in up to 3 centers in Brazil, over one year of recruitment.

Description

Inclusion Criteria:

• Subject's parent or legal guardian has provided signed eICF.
• Subject with SMA, genetically confirmed: with a bi-allelic mutation in the SMN1 gene, and a clinical diagnosis of SMA Type 1 or up to 3 copies of the SMN2 gene.
• Subject treated* with Onasemnogene Abeparvovec (Zolgensma®) prior to enrolling in this study.

Subjects treated with nusinersen or risdiplam prior to Onasemnogene Abeparvovec (Zolgensma®) can be enrolled if currently not receiving it.

*Subjects can be enrolled in this study on the day treated with Onasemnogene Abeparvovec (Zolgensma®) or if prior medical history is available to complete all assessments retrospectively, in accordance with local ethical requirements.

• Subject and parent/guardian are willing and able to comply with the phone contacts through the course of the study

Exclusion Criteria:

• Patients currently enrolled in any interventional clinical trial** other than the phase IV OFELIA trial will be excluded from the study.

  • Subjects who were enrolled in a clinical trial (independently of the disease indication and interventional treatment) but are not currently enrolled, can be included in this study.

During the follow-up, subjects who enroll any clinical trial with pharmacological intervention will discontinue from this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Spinal Muscular Atrophy Patients; Brazilian pediatric patients with a confirmed diagnosis of Spinal Muscular Atrophy treated with Onasemnogene Abeparvovec	Other: Onasemnogene Abeparvovec; Retrospective and prospective observational study. There is no treatment allocation.; Other Names: Zolgensma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment-emergent SAEs	Incidence and severity of treatment-emergent Serious AEs (SAEs)	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who experience at least one AESI and number of patients by AESI	Adverse Event of Special Interest: thrombocytopenia, hepatotoxicity, thrombotic microangiopathy (TMA), dorsal root ganglia toxicity, cardiac AEs, new malignancies, new incidence of neurologic, autoimmune, and hematologic disorder	Up to 15 years
Number of patients who have survived and have not required permanent ventilatory assistance	Evaluation of permanent ventilatory assistance, defined as requiring invasive ventilation(tracheostomy), or respiratory assistance for 16 or more hours per day (including non-invasiveventilatory support) continuously for 14 or more days in the absence of an acute reversible illness,excluding perioperative ventilation.	Up to 15 years
Time until death or the need for permanent ventilatory assistance	Evaluation of permanent ventilatory assistance, defined as requiring invasive ventilation(tracheostomy), or respiratory assistance for 16 or more hours per day (including non-invasiveventilatory support) continuously for 14 or more days in the absence of an acute reversible illness,excluding perioperative ventilation.	Up to 15 years
Number of patients who achieve each Developmental Motor Milestone	Evaluation of WHO Developmental Milestones: sitting without support, hands, and knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone.	Up to 15 years
Number of patients who achieve each WHO Developmental Milestone within age percentiles	Evaluation of WHO Developmental Milestones: sitting without support, hands, and knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone.	Up to 15 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): September 30, 2038
• Study Completion (Estimated): September 30, 2038

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Actual): August 31, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: NIS; Spinal Muscular Atrophies;; Onasemnogene Abeparvovec;; Brazil
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Atrophy; Muscular Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: COAV101ABR01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO