Clinical Research Directory

Outcome Measures and Biomarkers in a Cohort of Spinal Muscular Atrophy Type III/ IV Patients

The "SMOB" project intends to contribute to fill the gap with reliable and operational outcome measures for type III and IV SMA. In analysing the reliability in imaging (spinal and muscular), electrophysiology analysis (MUNIX), and evaluate the evolution of respiratory function for 50 patients' cohort. The investigators would also take the opportunity to collect biologic samples in order to investigate genetic markers and to assess quality of life of patients by QoL-gNMD questionnaire. The investigators aim to build a database that will allow us to evaluate the effectiveness of a new therapy for adult SMA patients by studying the natural history of the disease. The investigators have distributed the various expertise in Work Package where several centers are involved. This study is original in that it evaluates the parameters of qMRI and MUNIX in correlation with blood biomarkers. To our knowledge, there are no quantitative MRI (spinal and muscular) biomarkers and/or electrophysiological (MUNIX technique) highlighted for tracking the progression of the adult form of SMA type III and IV. This pilot study would allow identification of predictive markers of the disease progression, and to have validated, sensitive to change and relevant measurement tools that could be used as endpoints in future therapeutic trials.

ASsessing The REAl-world Safety & Effectiveness of Spinal Muscular Atrophy Participants Treated With Intrathecal Onasemnogene Abeparvovec-brve (OAV101B) (ITVISMA®): A U.S. Pragmatic Multicenter Study (STREAM)

The primary purpose is to address critical evidence in the treatment landscape for Spinal Muscular Atrophy (SMA), specifically focusing on the intrathecal formulation of onasemnogene abeparvovec-brve (ITVISMA®). U.S. Pragmatic Multicenter Study (STREAM).

Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy - Upper Limb

Spinal cord stimulation (SCS) has shown remarkable efficacy in restoring motor function in people with spinal cord injury by recruiting afferent input to enhance the responsiveness of spared neural circuits to residual cortical inputs. This pilot will test if SCS can show evidence to improve motor deficits in people with Type 2, 3, or 4 spinal muscular atrophy (SMA). The investigators will enroll up to six subjects with Type 2, 3, or 4 SMA aged 16 or older that show quantifiable motor deficits of the upper body. The investigators will then implant the subjects with percutaneous, linear spinal leads near the cervical spinal cord for a period of up to 29 days. Although these leads are not optimized for motor function but rather for their clinically approved indication of treating pain, the investigators believe they provide a safe technology enabling our team to perform scientific measurement necessary to evaluate potential for effects of SCS in motor paralysis with SMA. After the end of the study, the leads will be explanted.

Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)

A multi-center, longitudinal, prospective, non-comparative study to investigate the long-term safety and effectiveness of risdiplam, prescribed based on clinician judgment as per the Evrysdi® U.S. Package Information (USPI) in adult and pediatric participants with SMA. In this study, participants will be followed for approximately 24 months from enrollment or until withdrawal of consent, loss to follow-up, or death. Participants who discontinue risdiplam may still remain in the study if they agree to continue participating in the follow-up assessments. An optional sub-study was planned to assess the feasibility, acceptability, and adherence of remote assessment of motor and bulbar functions in participants with SMA using wearable and smartphone-based biosensors. This substudy was withdrawn upon implementation of protocol version 4.

A Registry of Cases of Spinal Muscular Atrophy

Because no long-term record of prenatal Spinal Muscular Atrophy (SMA) treatment exists, this study will address an important gap in the understanding of the safety and benefit of treatment while in the womb. The registry will help guide best practices for monitoring pregnant women and their fetus with SMA, if treated with a medication while in the womb, and to follow the baby after birth for signs of safety and added benefit birth and support future research and study development.

A Study of the Safety and Effectiveness of Onasemnogene Abeparvovec (Zolgensma) Intrathecal Injection in Spinal Muscular Atrophy Patients

This study aims to assess the safety and effectiveness of onasemnogene abeparvovec intrathecal injection in spinal muscular atrophy (SMA) patients in clinical practice in Japan. This is a non-interventional study and does not impose a therapy protocol, diagnostic/therapeutic procedure, or a visit schedule. Patients will be treated according to the Japan package insert. Data will be collected using a case registration form (CRF) completed by the investigator at each study site.

A Real-World Medical Chart Review of Spinal Muscular Atrophy Patients Treated With Onasemnogene Abeparvovec in Saudi Arabia

The aim of this retrospective medical chart review is to describe the clinical outcomes, clinical characteristics, and demographics of patients with spinal muscular atrophy (SMA) type 1 treated with onasemnogene abeparvovec (OA) at a single clinical center in Saudi Arabia. The study will use secondary data collected from the electronic medical records of SMA type 1 patients.

Characterizing Perceived Physical Fatigability in Nusinersen-treated SMA

The purpose of this project is to investigate the utility of the SMA EFFORT, an SMA-specific patient-reported outcome measure, to assess perceived physical fatigability that is anchored to intensity and duration of activities. We aim to characterize perceived physical fatigability (PPF) in a diverse cohort of people with SMA (pwSMA) and evaluate the change of PPF before and after nusinersen dosing.

A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy

This double-blind, Phase 2, multiple-dose study will be conducted to evaluate the PK/PD, efficacy, safety, and tolerability of apitegromab in subjects \<2 years old with 5q autosomal recessive SMA who have delayed motor milestones for their age attributed to SMA at the discretion of the Investigator or a Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score \<55.

A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years With Spinal Muscular Atrophy (SMA) Who Are Either New to SMA Treatment or Were Previously Treated With Risdiplam

In this study, researchers will learn more about the effects and safety of BIIB115, also known as salanersen. Specifically, researchers will learn more about how salanersen works in individuals with SMA who are between the ages of 15 and 60 years old. In most people living with SMA, changes to or a lack of a gene called survival motor neuron 1 (SMN1) - often referred to as gene mutations or variants - affect how this gene works. As a result, their bodies produce less SMN protein. Without enough of this protein, motor neurons and muscles cannot work properly. There is a similar gene called SMN2 that produces SMN protein, but it usually does not produce enough SMN protein on its own to make up for the changes in the SMN1 gene. Salanersen is a drug designed to help the SMN2 gene to make more working SMN protein. In this study, there will be 2 groups of participants: a group who has never received treatment for SMA before joining this study, and a group who has been treated with risdiplam, an approved drug for SMA . Those participants must not have received any other SMA treatments before and will need to stop their risdiplam treatment for the duration of the study. The main goal of this study is to learn more about how salanersen affects the participants' motor function. Researchers will use different tests and questionnaires to learn if motor function is changing over the study duration. The main question researchers want to answer in this study is: • For the group who has never been treated for SMA, how much do scores on the HFMSE movement test change at 12 months compared to the beginning of the study? The Hammersmith Functional Motor Scale - Expanded (HFMSE) has 33 activities that are scored which include sitting, lying down, walking, jumping, and more. Researchers will also learn more about: * The effects on participants' motor function and how well their nerves and muscles function. * The effects on participants' overall sense of change and how they perform daily activities. * How many participants have adverse events or serious adverse events. Adverse events are health problems that may or may not be caused by the study drug. * How much salanersen gets into the fluid surrounding the brain and spinal cord. * How much salanersen gets into the blood. This study will be done as follows: * First, participants will be screened to check if they can join the study. The screening period may be up to 4 weeks. * This is an "open-label" study. This is a study in which the participants, study doctor, and site staff will know that participants are receiving salanersen. * All participants will receive salanersen through an intrathecal injection, or one that is given into the fluid surrounding the brain and spinal cord. * Participants will receive salanersen once every year for a total of 5 times throughout the study. * Including screening, participants will have 17 study visits and 9 telephone calls during this study, which will last up to 61 months in total.

Acceptability, Feasibility, Safety and Efficacy of a Optimized Rehabilitation Program for Treated Patients With Spinal Muscular Atrophy (SMA).

The goal of this study is to investigate the acceptability, feasibility, safety and efficacy of an optimized rehabilitation program for treated patients with spinal muscular atrophy (SMA) compared to the current rehabilitation program in the United Kingdom. The aim is to provide patients with more hands on physiotherapy and access to rehabilitation devices at home to support parents currently providing rehabilitation on their own.

COMMAND Early Feasibility Study: Implantable BCI to Control a Digital Device for People With Paralysis

The Synchron motor neuroprosthesis (MNP) is intended to be used in subjects with severe motor impairment, unresponsive to medical or rehabilitative therapy and a persistent functioning motor cortex. The purpose of this research is to evaluate safety and feasibility. The MNP is a type of implantable brain computer interface which bypasses dysfunctional motor neurons. The device is designed to restore the transmission of neural signal from the cerebral cortex utilized for neuromuscular control of digital devices, resulting in a successful execution of non-mechanical digital commands.

Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab

The ONYX study is an Open-Label, Multicenter, Extension study that will evaluate the long-term safety and efficacy of Apitegromab in Patients with Type 2 and Type 3 SMA who have completed TOPAZ or SAPPHIRE.

UK SMA Patient Registry

Spinal muscular atrophy (SMA) is a form of motor neuron disease, most commonly caused by a mutation in the survival motor neuron 1 gene (SMN1) which results in a wide disease spectrum affecting children and adults. It is an autosomal recessive disorder and is therefore caused by inheritance of a mutated gene from each parent. All forms of SMA have an estimated combined incidence of 1 in 6,000 to 1 in 10,000 live births, with a carrier frequency of 1/40 to 1/60. The patient registry aims to facilitate a questionnaire-based research study in order to better characterise and understand the disease in the UK and in Ireland. Entry is via self-registration over a secure internet connection (https://www.sma-registry.org.uk/). Online, patients are asked to read an information sheet about the research project and then indicate their consent to demonstrate willingness to participate. Following online consent, subjects will be entered into the registry. This is an on-going database and all participants are invited to update their information on a biannual basis.

Study of an Intrathecal Port and Catheter System for Subjects With Spinal Muscular Atrophy

The primary objective of the clinical investigation is to demonstrate successful clinical use of the ThecaFlex DRx™ System in delivering nusinersen in subjects with spinal muscular atrophy (SMA). All enrolled subjects will undergo implantation of the investigational device (ThecaFlex DRx™ System) and will be followed for 12 months after receiving the implant. The 12-month data will be used to assess the primary endpoint support a Pre-Market Approval (PMA) application.

Equine-Assisted Physiotherapy for Spinal Muscular Atrophy

This prospective interventional study evaluates the immediate and sustained effects of intensive equine-assisted physiotherapy in children with spinal muscular atrophy (SMA). The study compares an intensive equine-assisted physiotherapy program (NEUROEQUIP-SMA) with an individualized physiotherapy program based on SMA standard of care and neuroproprioceptive facilitation and inhibition principles (SMA-SOC-N). Both interventions are delivered as intensive 6-day rehabilitation programs. Outcomes include motor function, postural control, respiratory function, movement quality assessed by three-dimensional motion analysis, neuromuscular activity, quality of life, and selected molecular biomarkers. The study also evaluates the safety and tolerability of intensive rehabilitation in children with SMA.

Spinal Muscular Atrophy and School Transitions

A qualitative questionnaire-based study to explore the experiences of children and young people with Spinal Muscular Atrophy (SMA) and their families regarding school transition and educational participation. The study objectives: To identify barriers to successful educational transition. To advocate for patients and families during the transitional process. To explore experiences of inclusion, access and support within school settings. To understand the coordination between education, healthcare and support services. To inform the development of practical, patient-centred guidance to improve educational transitions for children and young people with SMA.

Effects of Developmental Support for Mothers of Infants With Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder causing progressive muscle weakness and atrophy. This mixed-methods study aims to provide developmental support to mothers of infants (aged 12-36 months) with SMA Type 1 and to evaluate its impact on infants' developmental outcomes and mothers' developmental knowledge. Participants included eight mothers of infants/children diagnosed with SMA Type 1 who were recruited through purposive sampling from a university hospital. Quantitative data were collected using a General Information Form, the Ages and Stages Questionnaires (ASQ), the Ages and Stages Questionnaires: Social-Emotional (ASQ-SE), and the Caregiver Knowledge of Child Development Inventory (CKCDI). Qualitative data were obtained through semi-structured interviews exploring mothers' experiences with the developmental support program. The intervention consisted of a 12-week online developmental support program delivered once a week for 90 minutes. Outcome assessments were conducted at baseline, immediately after the intervention, and four weeks after the intervention (follow-up assessment) to evaluate the sustainability of the intervention effects.

Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies

In this observational study, researchers are looking at the effects of spinal muscular atrophy (SMA) drugs on the muscles and nerve cells in patients with SMA. Primary Objectives * To evaluate the feasibility and reliability of performing MR functional imaging in exercising muscle in patients with SMA. * To evaluate patients with SMA types 2 and 3 at baseline and longitudinally at 6 and 12 months Secondary Objectives * To describe the MR functional bioenergetics response in muscles in five potential groups of patients with spinal muscular atrophy: untreated, actively treated with nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®), actively treated with risdiplam (Evrysdi®), switching from Spinraza or Zolgensma to Evrysdi and initiating combination therapy of Spinraza or Zolgensma with Evrysdi . * To identify changes in motor function in patients with SMA types 2 and 3 who initiate treatment with risdiplam. * To obtain biomarkers in blood, urine, and muscle tissue to provide proof-of-concept support for risdiplam effect on skeletal muscle. * To obtain quality of life and disability data from participants in this study.

Early Check: Expanded Screening in Newborns

Early Check provides voluntary screening of newborns for a selected panel of conditions. The study has three main objectives: 1) develop and implement an approach to identify affected infants, 2) address the impact on infants and families who screen positive, and 3) evaluate the Early Check program. The Early Check screening will lead to earlier identification of newborns with rare health conditions in addition to providing important data on the implementation of this model program. Early diagnosis may result in health and development benefits for the newborns. Infants who have newborn screening in North Carolina will be eligible to participate, equating to over 120,000 eligible infants a year. Over 95% of participants are expected to screen negative. Newborns who screen positive and their parents are invited to additional research activities and services. Parents can enroll eligible newborns on the Early Check electronic Research Portal. Screening tests are conducted on residual blood from existing newborn screening dried blood spots. Confirmatory testing is provided free-of-charge for infants who screen positive, and carrier testing is provided to mothers of infants with fragile X. Affected newborns have a physical and developmental evaluation. Their parents have genetic counseling and are invited to participate in surveys and interviews. Ongoing evaluation of the program includes additional parent interviews.

An Open Label Study of Gene Therapy Product (Vesemnogene Lantuparvovec) in Spinal Muscular Atrophy

This is an interventional study to evaluate safety and efficacy of AAV-hSMN1 in spinal muscular atrophy patients.

Safety and Efficacy of NMD670 in Ambulatory Adult Patients With Type 3 Spinal Muscular Atrophy

The purpose of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of NMD670 in the treatment of ambulatory adults with spinal muscular atrophy type 3

A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy

This trial will study the efficacy and safety of taldefgrobep alfa as an adjunctive therapy for participants who are already taking a stable dose of nusinersen and/or risdiplam and/or have a history of onasemnogene abeparvovec, compared to placebo.

A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)

In this study, researchers will learn more about the use of a higher dose of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study will focus on teenagers and adults who are unable to walk on their own and who have previously taken another drug for SMA called risdiplam. The main goal of this study is to learn about the effect of high dose (HD) nusinersen on muscle and movement ability (motor function) in SMA. The main question that researchers want to answer is: \- How do the scores of a movement test called the Revised Upper Limb Module change from the start of treatment? The Revised Upper Limb Module is a test used to measure a participant's ability to do specific tasks that involve their shoulders, arms, wrist, elbows, and hands. It measures the changes in their abilities over time. Researchers will also learn more about the safety of HD nusinersen. They will check participants for adverse events and changes in vital signs, heart tests, and laboratory tests including blood and urine tests. The study will be done as follows: * Participants will be screened to check if they can join the study. * After screening, participants will enter the Core Treatment period. * At the start of the Core Treatment period, they will receive 2 "loading" doses of nusinersen. These are 50 mg doses of nusinersen given 2 weeks apart. * Afterwards, they will continue to receive "maintenance" doses of nusinersen once every 4 months. These doses will be 28 mg. * The Core Treatment period will last about 2 years, with a follow-up visit 4 months after the last dose. * Participants who complete the Core Treatment period will have the option to continue receiving 28 mg of nusinersen in the Long-Term Extension (LTE) period for about 2 years. There will also be a follow-up visit 4 months after the last dose. * Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back. * In total, participants will have up to 18 study visits. They will also be called by researchers after each dose of nusinersen. * Participants will stay in the study for about 4.5 years if they complete both the Core Treatment and LTE periods.