Investigating NMJ Defects in SMA Following Central and Peripheral SMN Restoration

NCT ID: NCT05219487

Last Updated: 2024-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-10-13

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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This is a proof of concept trial to investigate the impact of FDA approved therapy for adults with SMA on NMJ transmission. The study will enroll genetically confirmed adults with 5 q SMA treated with risdiplam for at least 12 months. Dosing will be weight- based as approved by the FDA (US Prescribing Information).

Assessments will include medical history, general physical and neurological examinations, vital signs, and the recording of adverse events. Diagnostic tests will include repetitive nerve stimulation (RNS), motor unit number estimation (MUNE), and decomposition EMG (dEMG). Further evaluations will utilize the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), the modified SMA Functional Rating Scale (SMAFRS), and the Fatigue Severity Scale (FSS). For ambulatory subjects, the assessment will include a six-minute walk test, while for non-ambulatory subjects, the Children's Hospital of Philadelphia Adult/Adolescent Test of Neuromuscular Disorders (CHOP INTEND) will be performed. Handheld dynamometry will be used to measure strength in bilateral shoulder abduction, elbow flexion, elbow extension, hip flexion, hip abduction, hip adduction, knee flexion, and knee extension.

The study aims to investigate the impact of Risdiplam on neuromuscular junction (NMJ) function by assessing changes in the percent decrement of the compound muscle action potential amplitude, as measured through 3 Hz repetitive nerve stimulation (RNS) of the spinal accessory nerve. These results will be compared to historical controls. Additionally, the study will evaluate the differences in strength, motor function, and electrophysiological test scores between groups, which will be stratified based on a 10% decrement cutoff. Further analysis will explore the association between these measures and percent decrement among ambulatory and non-ambulatory patients.

Conditions

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Spinal Muscular Atrophy

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Interventions

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Risdiplam

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)

Intervention Type DRUG

Other Intervention Names

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Evrysdi®

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Bakri Elsheikh

OTHER

Sponsor Role lead

Responsible Party

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Bakri Elsheikh

Professor of Neurology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Bakri Elsheikh, MBBS

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

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The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Gia Cinkay

Role: CONTACT

Phone: 614-366-9050

Email: [email protected]

Marco Tellez, CCRP

Role: CONTACT

Phone: 614-688-7837

Email: [email protected]

Facility Contacts

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Gia Cinkay

Role: primary

Marco Tellez, CCRP

Role: backup

Other Identifiers

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ML43109

Identifier Type: OTHER

Identifier Source: secondary_id

2021H0158

Identifier Type: -

Identifier Source: org_study_id