Status:

RECRUITING

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

Lead Sponsor:

St. Jude Children's Research Hospital

Collaborating Sponsors:

Genentech, Inc.

Conditions:

Spinal Muscular Atrophy

Eligibility:

All Genders

5-20 years

Brief Summary

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 f...

Detailed Description

This is an observational study to demonstrate the feasibility of performing MR functional imaging in exercising muscle in patients with SMA. The participants will be prescribed medication by their tre...

Eligibility Criteria

Inclusion

  • 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

Exclusion

  • 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.

Key Trial Info

Start Date :

October 29 2025

Trial Type :

OBSERVATIONAL

Allocation :

ESTIMATED

End Date :

March 1 2027

Estimated Enrollment :

24 Patients enrolled

Trial Details

Trial ID

NCT06532474

Start Date

October 29 2025

End Date

March 1 2027

Last Update

November 4 2025

Active Locations (1)

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105