Recruiting

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

Sponsor:

St. Jude Children's Research Hospital

Code:

NCT06532474

Conditions

Spinal Muscular Atrophy

Eligibility Criteria

Sex: All

Age: 5 - 20

Healthy Volunteers: Not accepted

Study Details

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 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.

Conditions

Spinal Muscular Atrophy

Study ID

NCT06532474

Start date

Oct 29, 2025

Status verified date

Jul, 2026

Completion date

Sep, 2028

Anticipated

Primary completion date

Sep, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 5 - 20

Healthy Volunteers: Not accepted

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, 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, HFMSE score at screening between 40 and 66.
SMN-directed therapy inclusion:

Current Evrysdi prescription (Group 1)

Must have Evrysdi prescription through their treating physician
If initiating combined therapy using Evrysdi with Spinraza or Zolgensma, must have not started Evrysdi treatment OR
Current Spinraza or Zolgensma prescription (Group 2)

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 (Group 3)

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 (Group 4)

Exclusion Criteria:

Any chronic medical condition, planned surgery, or treatment with a medication which would impact safety or participation of the study at the investigator's discretion
Inability to perform reliably the motor function testing or the exercise testing in the MR scanner.
Fat fraction > 35% in calf or bicep at screening MRI
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.

Study Design

Enrollment

24 participants

Anticipated

Interventions and Outcome Measures

Arms

Cohort 1

Current Evrysdi prescription or initiating combination therapy with Evrysdi to current Spinraza or Zolgenzma prescription

Cohort 2

Current Spinraza or Zolgensma prescription

Cohort 3

Changing from Spinraza or Zolgensma to Evrysdi

Cohort 4

Have never received any SMN-directed therapies

Primary outcome measure

Feasibility of performing MR functional imaging in SMA patients [ Time Frame: At baseline and at 6 months (+/- 14 days) ]
Reliability of performing MR functional imaging in SMA patients [ Time Frame: At baseline and at 6 months (+/- 14 days) ]
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (phosphocreatine) [ Time Frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days) ]
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (creatine concentrations) [ Time Frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days) ]
Measure intramuscular fat fraction in major muscle extremity in patients with SMA types 2 and 3 [ Time Frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days) ]
Measure electrophysiological tests of motor neuron function to repetitive nerve stimulation in patients with SMA types 2 and 3 [ Time Frame: At baseline and longitudinally at 6 (+/- 14 days) and 12 months (+/- 14 days) ]

Central Contacts and Locations

Central contacts

Jean Laboe, RN

901-595-1693 referralinfo@stjude.org

Locations

St. Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Jean Laboe, RN

901-595-1693 referralinfo@stjude.org

Principal Investigator:

Richard Finkel, MD

More Information

Sponsor

St. Jude Children's Research Hospital

Last update posted

Jul 9, 2026

Last verified

Jul, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by St. Jude Children's Research Hospital on 2026-07-09.