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

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · Jul 29, 2024

Keywords

ClinConnect Summary

This clinical trial is studying the effects of different treatments for spinal muscular atrophy (SMA) on muscles and nerve cells. Researchers want to see how well these treatments work, especially focusing on patients with SMA types 2 and 3. They will use special imaging techniques to look at the muscles while they are exercising. The trial aims to gather information on how the treatments affect muscle function over time, as well as patients' quality of life.

To participate in this study, individuals must be between 5 and 20 years old, with a confirmed genetic diagnosis of SMA. They should also be either non-ambulatory (meaning they cannot walk independently) or ambulatory (able to walk unassisted). Participants can include those who are currently receiving treatment with specific medications for SMA or those who have never received these treatments before. Throughout the trial, participants can expect to undergo various tests and assessments to monitor their muscle function and overall health. This study is currently recruiting participants, and it’s a great opportunity for those eligible to contribute to important research that may help improve SMA treatments in the future.

Gender

ALL

Eligibility criteria

• Inclusion 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
• Exclusion Criteria:
• • 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.