RECRUITING

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

Conditions

Spinal Muscular Atrophy Spinal Muscular Atrophy (SMA)SMA drugs Responses of Skeletal Muscle SMN-directed therapies Eyrysdi Spinraza Zolgensma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 the leg muscles in four potential groups of patients with spinal muscular atrophy: untreated, actively treated with nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®), actively treated with risdiplam (Evrysdi®), and switching from Spinraza or Zolgensma to 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.

Official Title

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

Quick Facts

Study Start:2025-10

Study Completion:2027-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06532474

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:5 Years to 20 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Not specified

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Genetic confirmation of SMA with homozygous deletion of SMN1 or compound heterozygous deletion/mutation of SMN1 * Two, three, or four copies of SMN2 * Age 5 to 20 years * Non-ambulatory participants: maximum function sitting or standing with support, never walked independently, still able to sit independently for 5 seconds at screening, with active ankle plantar flexion strength of at least 3 N with hand-held myometry and capable of performing repetitive maximal plantar flexion effort for 120 seconds. HFMSE score at screening between 10 and 45 points. * Ambulatory participants: minimum function of independent walking, able to walk unassisted a minimum of 100 meters at screening, ankle plantar flexion strength of at least 10 N with hand-held myometry and capable of performing repetitive maximal plantar flexion for 120 seconds. HFMSE score at screening between 40 and 60. * SMN-directed therapy inclusion: * Current Evrysdi prescription * Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR * Current Spinraza or Zolgensma prescription * For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule * For patients on Zolgensma, must have been dosed at least one year prior to screening * Must have Spinraza or Zolgensma prescription through their treating physician OR * Changing from Spinraza or Zolgensma to Evrysdi * For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule * For patients on Zolgensma, must have been dosed at least one year prior to screening * Must have voluntarily decided to switch therapies based on discussion with their treating physician * Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR * Have never received any SMN-directed therapies	* Labs at screening that are abnormal and identified as clinically significant by the PI: CBC, and CMP, liver function tests (over twice the upper limit of normal), PT/PTT, urine protein of 2+ or greater. * Inability to perform reliably the motor function testing or the exercise testing in the MR scanner. * Treatment with a possible SMA-enhancing or mitochondrial-enhancing medication, unless discontinued within 3 months prior to screening: oral albuterol, hydroxyurea, phenylbutryate, valproic acid, creatine, l-carnitine, or other mitochondrial type supplement (riboflavin, lipoic acid, etc.). A daily multivitamin and Vitamin D supplement and intermittent inhaled albuterol are permitted if the dosage is unchanged during the study. * Need for routine non-invasive ventilation support. * Non-oral nutritional support, e.g., gastrostomy tube feeding. * Any ferrous metal implants (e.g., spinal rods) that preclude testing in a MR scanner.

Inclusion Criteria

Exclusion Criteria

* Genetic confirmation of SMA with homozygous deletion of SMN1 or compound heterozygous deletion/mutation of SMN1
* Two, three, or four copies of SMN2
* Age 5 to 20 years
* Non-ambulatory participants: maximum function sitting or standing with support, never walked independently, still able to sit independently for 5 seconds at screening, with active ankle plantar flexion strength of at least 3 N with hand-held myometry and capable of performing repetitive maximal plantar flexion effort for 120 seconds. HFMSE score at screening between 10 and 45 points.
* Ambulatory participants: minimum function of independent walking, able to walk unassisted a minimum of 100 meters at screening, ankle plantar flexion strength of at least 10 N with hand-held myometry and capable of performing repetitive maximal plantar flexion for 120 seconds. HFMSE score at screening between 40 and 60.
* SMN-directed therapy inclusion:
* Current Evrysdi prescription
* Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR
* Current Spinraza or Zolgensma prescription
* For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule
* For patients on Zolgensma, must have been dosed at least one year prior to screening
* Must have Spinraza or Zolgensma prescription through their treating physician OR
* Changing from Spinraza or Zolgensma to Evrysdi
* For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule
* For patients on Zolgensma, must have been dosed at least one year prior to screening
* Must have voluntarily decided to switch therapies based on discussion with their treating physician
* Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR
* Have never received any SMN-directed therapies

* Labs at screening that are abnormal and identified as clinically significant by the PI: CBC, and CMP, liver function tests (over twice the upper limit of normal), PT/PTT, urine protein of 2+ or greater.
* Inability to perform reliably the motor function testing or the exercise testing in the MR scanner.
* Treatment with a possible SMA-enhancing or mitochondrial-enhancing medication, unless discontinued within 3 months prior to screening: oral albuterol, hydroxyurea, phenylbutryate, valproic acid, creatine, l-carnitine, or other mitochondrial type supplement (riboflavin, lipoic acid, etc.). A daily multivitamin and Vitamin D supplement and intermittent inhaled albuterol are permitted if the dosage is unchanged during the study.
* Need for routine non-invasive ventilation support.
* Non-oral nutritional support, e.g., gastrostomy tube feeding.
* Any ferrous metal implants (e.g., spinal rods) that preclude testing in a MR scanner.

Contacts and Locations

Study Contact

Jean Laboe, RN

CONTACT

901-595-1693

referralinfo@stjude.org

Principal Investigator

Richard Finkel, MD

PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Study Locations (Sites)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

United States

Collaborators and Investigators

Sponsor: St. Jude Children's Research Hospital

Richard Finkel, MD, PRINCIPAL_INVESTIGATOR, St. Jude Children's Research Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-10

Study Completion Date2027-03

Study Record Updates

Study Start Date2025-10

Study Completion Date2027-03

Terms related to this study

Keywords Provided by Researchers

Spinal Muscular Atrophy (SMA)
SMA drugs
Responses of Skeletal Muscle
SMN-directed therapies
Eyrysdi
Spinraza
Zolgensma

Additional Relevant MeSH Terms

Spinal Muscular Atrophy