Characterization of the Clinical-epidemiological Profile of Patients With SMA5q Types II and III: Observational Study

Characterization of the Clinical-epidemiological Profile of Patients With Spinal Muscular Atrophy (SMA) 5q Types II and III in Follow-up in the Brazilian Unified Public Health System: A Cross-sectional Observational Study (Registry)

This study aims to characterize the clinical-epidemiological profile and baseline characteristics of patients with spinal muscular atrophy (SMA) 5q types II and III in follow-up at the Brazilian Unified Public Health System (SUS). The study data will be based on patients´ medical records from several Brazilian public hospitals, which will be defined by the Brazilian Ministry of Health (MS).

Study Overview

• Status: Completed
• Conditions: Spinal Muscular Atrophy
• Intervention / Treatment: Drug: Nusinersen Injectable Product

Detailed Description

This is a retrospective cross-sectional observational study to characterize the clinical and epidemiological profile of patients with spinal muscular atrophy (SMA) 5q types II and III, in follow-up at the Brazilian Unified Public Health System (SUS). This study aims to provide baseline data, which in the future may be used by the Brazilian Ministry of Health (MS) to assess the effectiveness of nusinersen. The clinical and epidemiological data will be collected from patients´ medical records, such as the score for the Hammersmith Functional Motor Scale - Expanded (HFMSE) and the Revised Upper Limb Module (RULM) at baseline, the WHO motor milestones at baseline, disease duration, age at the time of disease diagnosis, age at the time of disease screening, SMN2 (gene copy number), history of hospitalizations, history and characterization of previous surgical procedures, treatment dosage used, patient caregiver´s profile (ie, a family member or companion, who is responsible for taking care of the patient for most of the time). Other variables of interest that will also be collected are patient´s age and gender, geographic distribution, attending physician expertise and care structure where the patients were treated. The data acquisition will be performed using a paper and eletronic CRF (Case report Form). Written informed consent will be obtained from patients who meet the study elegibility criteria. The study will be performed in Brazilian public hospitals (centers) that are able to provide the treatment with nusinersen under the SUS scope. The total sample of patients and number of participating centers will be defined by the MS - SCTIE (Secretariat of Science, Technology and Strategic Supplies)/ DECIT (Department of Science and Technology). However, the initial estimation is a sample of 100 patients to be included in 10-15 centers.

• Study Type: Observational
• Enrollment (Actual): 155

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • Universidade Federal De Minas Gerais - Hospital das Clínicas
  • Campinas, Brazil
    • Hospital de Clínicas da Universidade Estadual de Campinas - Unicamp
  • Curitiba, Brazil
    • Associação Hospitalar de Prot Infancia Dr Raul Carneiro - Hospital Infantil Pequeno Príncipe
  • Fortaleza, Brazil
    • Hospital Infantil Dr. Albert Sabin
  • Porto Alegre, Brazil
    • Hospital de Clinicas de Porto Alegre
  • Rio De Janeiro, Brazil
    • Hospital Universitário Pedro Ernesto
  • Rio De Janeiro, Brazil
    • Instituto de Puericultura e Pediatria Martagão Gesteira da Universidade Federal do rio de Janeiro - UFRJ
  • São Paulo, Brazil
    • Universidade Federal de São Paulo
  • São Paulo, Brazil
    • Hospital das Clínicas da Faculdade de Medicina de São Paulo - HCFMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Spinal Muscular Atrophy (SMA) 5q types II and III in follow-up in the Brazilian Unified Public Health System (SUS), undergoing treatment with nusinersen or not. For each patient included, a first-degree family member or companion responsible for taking care of the patient for most of the time will also be included, if they agree to participate in the study.

Description

Patient Eligibility Criteria:

Inclusion Criteria:

• Participants of both sexes, in any age group, who have a clinical diagnosis of SMA 5q type II or type III, in follow-up at SUS, undergoing treatment with nusinersen or not
• Clinical and molecular diagnosis of SMA 5q type II (disease started after 6 months of age), or Clinical and molecular diagnosis of SMA 5q type III (disease started after 18 months of age)

Exclusion Criteria:

• Refusal to provide written informed consent (either the patient or a legal representative)
• Symptom onset after 19 years of age
• Need for invasive ventilatory support for 16 hours or more per day for more than 21 consecutive days
• Be participating or have participated in another clinical study aimed at specific treatment of SMA 5q other than with the drug nusinersen
• Having undergone treatment with gene therapy

Caretaker Eligibility Criteria:

Inclusion Criteria:

• First-degree family member or companion responsible for taking care of the patient with clinical diagnosis of SMA 5q type II or type III

Exclusion Criteria:

• Illiteracy
• Refusal to participate in the study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treated with nusinersen at SUS; Patients with Spinal Muscular Atrophy (SMA) 5q types II and III treated with nusinersen in the Brazilian Unified Public Health System	Drug: Nusinersen Injectable Product; The patient´s treatment is provided by SUS. The following dosage scheme of nurinersen is the one approved by ANVISA (Brazilian National Health Surveillance Agency): Nusinersen, 12 mg (5 mL) on days 0 (zero), 14 and 28. A fourth dose will be on day 63 with a maintenance dose once every 4 (four) months. The study will NOT have direct influence on the care received by patients. Data on adherence, interventions, hospitalizations, mechanical ventilation, procedures and adverse events will be obtained from the patients´ medical records.; Other Names: Spinraza
With indication to receive nusinersen at SUS; Patients with Spinal Muscular Atrophy (SMA) 5q types II and III with indication, but not yet receiving nusinersen treatment in the Brazilian Unified Public Health System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Hammersmith Functional Motor Scale	Hammersmith Functional Motor Scale-Expanded (HFMSE) scores range from 0 to 66, with higher scores indicating better motor function.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Revised Upper Limb Module	Revised Upper Limb Module (RULM) scores range from 0 to 37, with higher scores indicating better function.	In the inclusion of the study
WHO motor milestones	The six World Health Organization (WHO) motor milestones are sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone, and walking alone.	Unique evaluation at the time of inclusion
Disease duration	Time between diagnosis and age at inclusion in the study	At the time of inclusion in the study
Clinical features	SMN2 (gene copy number);	Unique evaluation
History of hospitalizations	Records of need for hospitalizations	Documented in the period prior to the inclusion of the study
History and characterization of previous surgical procedures	History of comorbidities	In the period prior to the inclusion of the study
Treatment with nusinersen	To undergo intrathecal administration of nusinersen at a dose of 12 mg	Registration of the dose used at the time of inclusion in the study

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Ministry of Health, Brazil
• Investigators: Study Chair: Vanessa Teich, PhD, Hospital Israelita Albert Einstein; Study Chair: Edmar Zanoteli, PhD, University of Sao Paulo; Principal Investigator: Elice Batista, PhD, Hospital Israelita Albert Einstein

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 27, 2020
• Primary Completion (ACTUAL): April 23, 2021
• Study Completion (ACTUAL): April 23, 2021

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (ACTUAL): May 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Spinal Muscular Atrophy; Nusinersen; Spinal Muscular Atrophy type II; Spinal Muscular Atrophy type III; Mutation in SMN1
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: 27245419.0.0000.5259

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No