Spinraza in Adult Spinal Muscular Atrophy (SAS)

A Prospective, Multi-center, Observational Study of the Safety, Tolerability and Effectiveness of SPINRAZA® (Nusinersen) in Adult Patients With Spinal Muscular Atrophy

This is a longitudinal, observational study of adult patients with genetically confirmed chromosome 5q SMA to examine the safety, tolerability, and effectiveness of SPINRAZA® (nusinersen) for up to 30 months.

Study Overview

• Status: Active, not recruiting
• Conditions: Spinal Muscular Atrophy; Spinal Muscular Atrophy Type 3; Spinal Muscular Atrophy Type II
• Intervention / Treatment: Drug: Observational study to examine safety, tolerability, and effectiveness of SPINRAZA® prescribed as part of standard of care; Other: One time survey

Detailed Description

This is a prospective, longitudinal, multi-center, observational study designed to evaluate the safety, tolerability, and effectiveness of SPINRAZA® (nusinersen) in ambulatory and non-ambulatory adult patients with SMA. Subjects with SMA II/III that are 18 years to 70 years of age who are planning to initiate treatment with SPINRAZA® (nusinersen) as part of their clinical care plan will be enrolled in this study. This study does not provide SPINRAZA® (nusinersen) or cover costs associated with standard clinical care.These patients will be treated by their respective physicians according to standard clinical practice. Study visits, some of which including standardized assessments of strength and function, will occur at baseline, day 15 after treatment initiation, day 30, day 60, and then 4-month intervals through month 30.

After 30 months an additional cohort 2 was added. The approval date was March 13, 2023. The cohort 2 is a one time survey to gain a better understanding of this adult population and their treatment preferences.

• Study Type: Observational
• Enrollment (Estimated): 148

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital-Harvard University
  • Michigan
    • Owosso, Michigan, United States, 48867
      • Memorial Healthcare
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10003
      • New York University School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of the King's Daughthers
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with SMA that are 18 years to 70 years of age who are planning to initiate treatment with SPINRAZA® (nusinersen) as part of their clinical care plan.

For Cohort 2 - Subjects with SMA that are 18 years to 70 years with SMA type II/III.

Description

Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Males and females with SMA type II or type III, aged 18 to 70 years at the time of enrollment.
3. Genetic documentation of 5Q SMA homozygous gene deletion, mutation, or compound heterozygote.
4. Are treatment naïve for SPINRAZA® (nusinersen).
5. Have been prescribed SPINRAZA® (nusinersen) by the treating physician as part of their clinical care for SMA following the FDA approved prescribing information guidelines as follows: dose level (12 mg), dosing schedule (3 loading doses administered at 14-day intervals, and the fourth loading dose administered 30 days after the third dose and subsequent maintenance doses administered every 4 months) and safety lab monitoring (CBC, PT, INR, PTT, UA) done prior to each dose administration.
6. Believed to be able to complete all study procedures, measurements and visits.
7. Estimated life expectancy at least 30 months from first dosing, in the opinion of the Investigator.
8. Revised upper limb module (RULM) score ≥ 4 (more than marginal upper extremity function/strength.
9. Must meet either Group 1 or Group 2 criteria.

For Group 1 subjects:

1. May be ambulatory or non-ambulatory (defined as being wheelchair reliant at least 75% of time and unable to walk at least 10 meters without assistance).
2. RULM score of 4-34, inclusive.

For Group 2 subjects:

1. Ability to walk at least 10 meters without assistance (i.e., four point walking aid).
2. Be free of major orthopedic deformities that limit ambulation.
3. An ambulatory subject can qualify for both Group 1 and Group 2 if the RULM score is ≤ 34.

Exclusion Criteria:

1. Revised upper limb score ≤ 3.
2. Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for >16 hours during a 24-hour period, at screening.
3. Hospitalization for major medical event including: surgery (i.e., scoliosis surgery, other surgery), cardiac event, pulmonary event, or other major medical problem within 2 months of screening or planned major surgical procedure likely to impact the clinical assessments during the duration of the study. Outpatient surgical procedure (i.e., placement of feeding tube) is not considered an exclusionary major medical event.
4. Presence of a symptomatic severe active infection or illness during the screening period that is likely to impact the performance on the clinical assessments.
5. Prior exposure to SPINRAZA® (nusinersen).
6. Prior disorder, injury (e.g., upper or lower limb fracture) or surgical procedure which impacts the subject's ability to perform any of the outcome measure testing required in the protocol and from which the subject has not fully recovered or achieved a stable baseline.
7. Treatment with an investigational drug (e.g., oral albuterol/salbutamol, riluzole, carnitine, creatine, sodium phenylbutyrate, etc.), biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Patients using intrathecal drug delivery devices, including investigational devices with an active IDE designation in the United States, may be eligible but require Study PI approval prior to enrollment.
8. Any history of exposure to gene therapy, antisense oligonucleotide therapy, or cell transplantation that was intended for the treatment of SMA.
9. Ongoing medical condition that according to the Clinical Center Investigator would interfere with the conduct and assessments of the study. Examples are medical disability (e.g., wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromise the ability of the subject to undergo study procedures.

For Cohort 2 Inclusion criteria

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Males and females with SMA type II or type III, aged 18 to 70 years at the time of enrollment.
3. Genetic documentation of 5Q SMA homozygous gene deletion, mutation, or compound heterozygote.
4. Believed to be able to complete the structured interview.

Cohort 2 Exclusion Criteria

1. Ongoing medical condition that according to the Clinical Center Investigator would interfere with the conduct and assessments of the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; This is a prospective, longitudinal, multi-center, observational study designed to evaluate the safety, tolerability, and effectiveness of SPINRAZA® (nusinersen) in ambulatory and non-ambulatory adult patients with SMA. Subjects with SMA II/III that are 18 years to 70 years of age who are planning to initiate treatment with SPINRAZA® (nusinersen) as part of their clinical care plan will be enrolled in this study. This study does not provide SPINRAZA® (nusinersen) or cover costs associated with standard clinical care.These patients will be treated by their respective physicians according to standard clinical practice. Study visits, some of which including standardized assessments of strength and function, will occur at baseline, day 15 after treatment initiation, day 30, day 60, and then 4-month intervals through month 30.	Drug: Observational study to examine safety, tolerability, and effectiveness of SPINRAZA® prescribed as part of standard of care; This is an observational study of adult patients with SMA to examine the safety, tolerability, and effectiveness of SPINRAZA® (nusinersen) for up to 30 months.
Cohort 2; The cohort 2 is a one time survey to gain a better understanding of this adult population and their treatment preferences.	Other: One time survey; One time survey

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the 6-Minute Walk Test (6MWT) for ambulatory SMA patients	Assess effectiveness of SPINRAZA® (nusinersen) treatment on mobility and ambulation in ambulatory adult SMA patients, comparing changes in total distance walked in in six minutes from baseline until end of treatment at 30 months..	30 months
Change from baseline in Revised Upper Limb Module (RULM) for weak ambulatory and non-ambulatory SMA patients	Assess the effectiveness of SPINRAZA® (nusinersen) treatment on upper extremity function in ambulatory and non-ambulatory adult SMA patients, comparing change in RULM score from baseline until end of treatment at 30 months.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the demographic and clinical characteristics, disease burden, treatment preferences, and subjective assessments of disease progression	One time survey	6 months to 1 year

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Craig Zaidman, MD, Washington University School of Medicine

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.
• De Vivo DC, Hwu W-L, Reyna SP, et al. Interim efficacy and safety results from the phase 2 NURTURE study evaluating nusinersen in presymptomatic infants with spinal muscular atrophy (S46.003). Neurology 88(16 Suppl.): S46.003

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Motor Neuron Disease; Atrophy; Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood
• Other Study ID Numbers: 201805187

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