Investigating NMJ Defects in SMA Following Central and Peripheral SMN Restoration

NCT05219487 | Completed

• 2 other identifiers: 2021H0158ML43109
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an observational study to investigate the improvement of NMJ defects in adult patients with SMA following treatment with Risdiplam. Eligible patients will have received treatment with daily oral Risdiplam after receiving approval through their commercial insurance or drug assistance program. All subjects will be evaluated at one visit. Eligible subjects must have been receiving risdiplam for at least 12 months.

Conditions

Spinal Muscular Atrophy

Outcome Measures

Primary Outcomes (1)

• Decrement on repetitive nerve stimulation

  Change in the percent decrement of the compound muscle action potential amplitude assessed using 3 Hz repetitive nerve stimulation (RNS) of the spinal accessory nerve compared to historical controls. If CMAP amplitude is absent at spinal accessory nerve, SMA, ulnar CMAP will be used to assess NMJ transmission.

  Baseline

Secondary Outcomes (10)

• Six Minute Walk Test (6MWT) Total Distance

  Baseline

• Six Minute Walk Test Difference in Distance Between the First and Final minute

  Baseline

• Modified Spinal Muscular Atrophy Function Rating Scale (SMA-FRS)

  Baseline

• Revised Upper Limb Module (RULM)

  Baseline

• Hammersmith Functional Rating Scale (HFMSE)

  Baseline

Interventions

Risdiplam DRUG

Risdiplam is administered orally once daily and the recommended dosage is determined by age and body weight (see Table 1) \[as outlined in the US Prescribing Information for EVRYSDI™(risdiplam)\]. Table 1 Adult and Pediatric Dosing Regimen by Age and Body Weight: US Prescribing Information Age and Body Weight (Recommended Daily Dosage): 2 months to less than 2 years of age (0.2 mg/kg); 2 years of age and older weighing less than 20 kg (0.25 mg/kg); 2 years of age and older weighing 20 kg or more (5 mg)

Also known as: Evrysdi®

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will enroll genetically confirmed adults with 5 q SMA with electrodiagnostic evidence of NMJ defects treated with risdiplam for a duration of 12 months or longer.

You may qualify if:

• Signed Informed Consent Form
• Age 18-70 years at time of signing Informed Consent Form
• Able and willing to provide written informed consent and to comply with the program protocol according to ICH and local regulations
• Ability to comply with the study protocol, in the investigator's judgment
• Adequately recovered from any acute illness at the time of screening, and considered clinically well enough to participate, in the opinion of the treating physician
• Patients with retinopathy of prematurity should have evidence of stable disease
• Genetic confirmation of 5q SMA documented on standard genetic tests for the disorder
• Treated with risdiplam for a duration of 12 months or longer

You may not qualify if:

• Treatment with an investigational therapy within 180 days prior to initiation of study drug
• History of established diagnosis of neuromuscular junction disorder
• Co-morbid conditions that preclude travel or testing
• Patients who are, in the investigator's opinion, mentally or legally incapacitated to provide an informed consent

Sponsors & Collaborators

• Bakri Elsheikh: lead
• Genentech, Inc.: collaborator

Study Sites (1)

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Risdiplam

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Officials

• Bakri Elsheikh, MBBS

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: January 21, 2022
• First Posted: February 2, 2022
• Study Start: October 13, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (1)