Adults With SMA Treated With Nusinersen

Characterizing Longitudinal Outcomes in Adults With SMA Treated With Nusinersen

This is a single center, 22-month observational study of nusinersen treatment in adult patients with spinal muscular atrophy (SMA). There will be a total of seven visits. Nusinersen is provided as standard of care and not considered research in this study. Information will be collected regarding the general health, and function including muscle strength of, as well as any positive and/or adverse events experienced by the study participants.

Study Overview

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

Detailed Description

This is a single center, 22-month observational study of nusinersen treatment in adult patients with SMA. There will be a total of five visits. All subjects will be evaluated at a screening visit no more than four weeks before starting their standard of care nusinersen treatment to determine their eligibility for participation. Eligible patients will complete their standard induction intrathecal nusinersen treatment on day 1, 15, 29 and 60 followed by maintenance doses every four months. Subjects will be reevaluated after completing the loading doses at 2 months followed by every four-month evaluations for the total duration of the treatment of 22 months.

Currently, there is no data published on patients receiving this treatment over the age of 18. Without published data collected from research, it is difficult for adult patients to get approval from their insurance companies to receive this treatment. This study hopes to collect data, in order to make this treatment option easier for patients with SMA to access and in general learn how well nusinersen is working in adult patients with SMA overtime.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

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: Non-Probability Sample

Study Population

Adults with spinal muscular atrophy (SMA) as confirmed by clinical and genetic assessments.

Description

Inclusion Criteria:

1. Age 18 to 60 years
2. Genetic confirmation of 5q SMA documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder
3. SMN2 copy number of 3 or greater
4. Subjects must be able to walk thirty feet without assistance (i.e. no canes, walkers)
5. Interest in participating and the ability to meet the study requirements
6. Women of childbearing-age are required to be on birth control or abstain while participating in the research study

Exclusion Criteria:

1. Subjects with history of spinal disease that will interfere with the lumbar puncture procedure
2. Subjects with history of bacterial meningitis or encephalitis
3. Subjects with history of use of investigational drug treatment for SMA in the last six months, or plan on enrolling in any other treatment trial during the duration of this trial
4. History of treatment with gene therapy, stem cell or antisense oligonucleotide
5. Patients with co-morbid conditions that preclude travel, testing or study medications
6. Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing
7. Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

SMA nusinersen adult cohort; The nusinersen treatment will be given as standard of care. The treatment (which is NOT research, but the standard care) will be given by an injection into the cerebrospinal fluid (fluid in your spine) through a needle inserted into your lower back. Participants will receive a 12 mg (5 mL) dose during each administration/injection, which will occur on the following days: 1 (baseline), 15, 29, and 60. Following the 60 day treatment, participants will receive treatment every 4 months (6, 10, 14 etc.). After the 60 day, 6 month, 10 month, 14 month, 18 month and 22 month treatments the study team will see each participant afterwards to collect information to evaluate your general health, function and response to the treatment for the study.

Drug: nusinersen; SPINRAZA (nusinersen) is FDA approved to treat spinal muscular atrophy (SMA) through intrathecal injection.; Other Names: SPINRAZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strength	To evaluate the effect of nusinersen treatment on muscle strength in ambulatory SMA adults	22 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Six Minute Walk Test	6 Minute Walk Test (6WMT)	22 months
Change in Hammersmith Functional Motor Scale Expanded	Hammersmith Functional Motor Scale Expanded (HFMSE)	22 months
Change in SMA Functional Rating Scale	modified SMA Functional Rating Scale(SMA-FRS)	22 months
Change in Forced Vital Capacity	Forced Vital Capacity (FVC)	22 months
Change in Negative Inspiratory Force	Negative Inspiratory Force (NIF)	22 months
Change in lean muscle mass	Muscle mass measured using Dual-Energy X-Ray Absorptiometry (DXA)	22 months
Change in Quality of Life	Quality of life will be measured using 36-Item Short Form Survey (SF-36)	22 months
Change in Ulnar and Peroneal muscle measures	Compound Muscle Action Potential Amplitude (CMAP) will be recorded	22 months
Change in Motor Unit Number Estimation (MUNE)	Ulnar nerve (Recording at the Abductor Digiti Minimi muscle) MUNE scores will be recorded	22 months
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants who experience adverse outcomes	22 months

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: Biogen; Cure SMA

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): May 14, 2021
• Study Completion (ACTUAL): June 25, 2021

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (ACTUAL): October 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 22, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Spinraza; nusinersen
• 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; Atrophy; Motor Neuron Disease; Muscular Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: 2018H0311

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes