Effect of Nusinersen on Adults With Spinal Muscular Atrophy

Effect of Nusinersen on Motor Function in Adult Patients With Spinal Muscular Atrophy Types 2 and 3

Observational study of adult patients with spinal muscular atrophy types 2 and 3 receiving nusinersen

Study Overview

• Status: Completed
• Conditions: Adult Spinal Muscular Atrophy
• Intervention / Treatment: Drug: nusinersen

Detailed Description

Observational study to assess effects of nusinersen on motor function in adult patients with spinal muscular atrophy who are both ambulatory and non-ambulatory. Subjects will receive standard of care with nusinersen intrathecal injection and undergo baseline and every 6 month motor assessments and pulmonary function testing during the first two years of treatment with nusinersen.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• United States
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The population to be studied are a homogenous group of adult subjects with 5q SMA seeking treatment with nusinersen. The subjects will have a broad phenotype spectrum of motor weakness including ability to ambulate, non-ambulatory and varying degrees of upper limb motor function and respiratory and swallow abilities, with some more affected and requiring invasive ventilation or NIV, and/or PEG tubes for nutrition.

Description

Inclusion Criteria:

• Genetically confirmed 5q SMA
• ability to access intrathecal space for nusinersen injection

Exclusion Criteria:

• Renal impairment
• thrombocytopenia
• inability to access intrathecal space by CT or flouro guided injection

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects with spinal muscular atrophy types 2 and 3; Intrathecal nusinersen will be administered to all subjects per FDA approved label.	Drug: nusinersen; Subjects will receive nusinersen and be observed with motor assessments for 24 months; Other Names: Spinraza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quantitative motor function	Primary Endpoint: Change from baseline to end of study in quantitative motor strength by dynamometry of upper limb muscles - shoulder abduction and elbow flexion/extension.	Two years
Change in upper limb motor function	Change from baseline to end of study in upper limb module score	Two years
Change in 6 minute walk test in ambulatory patients	Change in 6 minute walk test from baseline to end of study	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary function by spirometry forced vital capacity (FVC)	Change in FVC from baseline to end of study	Two years
Change in 10 meter walk test in ambulatory patients	Change from baseline to end of study in the 10 meter walk test	Two years
Change in compound muscle action potential (CMAP) amplitude by nerve conduction velocity (NCV) criteria	Change from baseline to end of study in CMAP amplitude of responses from median, ulnar and peroneal motor nerves	Two years
Change in pulmonary function by spirometry forced expiratory volume (FEV)	Change from baseline to end of study in FEV	Two years

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Anthony Geraci, MD, Northwell Health

Publications and helpful links

General Publications

• Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752.
• Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, Iannaccone ST, Kirschner J, Kuntz NL, Saito K, Shieh PB, Tulinius M, Mazzone ES, Montes J, Bishop KM, Yang Q, Foster R, Gheuens S, Bennett CF, Farwell W, Schneider E, De Vivo DC, Finkel RS; CHERISH Study Group. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. 2018 Feb 15;378(7):625-635. doi: 10.1056/NEJMoa1710504.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): July 13, 2021
• Study Completion (Actual): July 13, 2021

Study Registration Dates

• First Submitted: March 10, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: 18-0149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No