Implantation of a device for delivering nusinersen in spinal muscular atrophy patients

Safety and Performance of the ThecaFlex DRx™ System Port and Catheter for Chronic Intrathecal Access, Cerebrospinal Fluid (CSF) Aspiration, and DElivery of Nusinersen in Spinal Muscular Atrophy (SMA) Patients Resistant to Lumbar PunctuRE Trial (PIERRE)

This study is testing a new device that delivers a treatment for spinal muscular atrophy directly into the spine to see if it is safe and works well for patients who have trouble with regular injections.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 3 Years and up
• Sex: All
• Sponsor: Alcyone Therapeutics, Inc (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 21 sites (Phoenix, Arizona and 20 other locations)
• Trial ID: NCT05866419 on ClinicalTrials.gov

What this trial studies

This clinical investigation aims to evaluate the safety and performance of the ThecaFlex DRx™ System, which is designed for the intrathecal delivery of nusinersen in patients with spinal muscular atrophy (SMA). Participants aged 3 years and older who are candidates for this treatment will undergo implantation of the device and will be monitored for 12 months post-implantation. The study is multicenter and non-randomized, focusing on subjects who are resistant to lumbar punctures due to various health concerns. The data collected will support a Pre-Market Approval application for the device.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 3 years or older diagnosed with SMA who require chronic intrathecal administration of nusinersen and are resistant to lumbar punctures.

Not a fit: Patients who do not have spinal muscular atrophy or those who are not candidates for nusinersen treatment will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a safer and more effective method for administering nusinersen to SMA patients who cannot undergo traditional lumbar punctures.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in the use of intrathecal delivery systems for other therapies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Subject is 3 years or older
2. Subject diagnosed with SMA who are candidates for Spinraza treatment as indicated in its label
3. Subject resistant to lumbar puncture (LP), where resistance is defined as:

   1. Subject with respiratory issues or other comorbidities who is at an increased risk for complications due to the need for repeat anesthesia and imaging radiation exposure to safely perform LP; or
   2. Subjects for whom the treating physician determines implantation of the ThecaFlex DRx™ System is otherwise in the subject's best interest
4. Subject has been prescribed nusinersen via chronic intrathecal bolus administration in accordance with the drug labeling and first port access of the ThecaFlex DRx system is planned within 2 weeks of implantation
5. Subject, per Investigator discretion, is able to undergo a percutaneous or open surgical procedure for index port and catheter implantation where at least 7 cm of the ThecaFlex DRx system catheter will be placed intrathecally
6. Subject (or subject's legally authorized representative) is willing and able to provide written informed consent; and
7. Subject and parent/caregiver able and willing to complete all clinical investigation procedures, measurements, and visits.

Exclusion Criteria:

1. Subject meets any of the contraindications for use of the ThecaFlex DRx™ System as outlined in the ThecaFlex DRx™ System Instructions for Use
2. Presence or history of (\< 6 months prior to the procedure): an implanted microinfusion pump, intrathecal catheter, or other intrathecal drug delivery devices/component, or implanted shunt for drainage of cerebrospinal fluid (CSF), or reservoir in the CSF space (note: any ThecaFlex Port and Catheter System must not be placed in the same location as a previous indwelling port and catheter)
3. Subject is pregnant or nursing or plans to become pregnant during the course of the clinical investigation
4. Any condition or event, which in the opinion of the Investigator may adversely affect the safety and effective implantation and use of the ThecaFlex DRx™ system or confound the clinical investigation, including:

   1. Severe structural impediment that may preclude safe implantation of the catheter and port
   2. Major medical events within 60 days prior to screening; or
   3. Relevant surgeries (e.g., head and neck, back, etc.) within 60 days prior to screening or planned during the duration of the clinical investigation
   4. Space-occupying lesion with mass effect
   5. Posterior fossa mass
   6. Arnold-Chiari malformation
   7. Coagulation abnormalities and/or thrombocytopenia
   8. Insufficient or inadequate skin or underlying fat to adequately protect the port or enough surface area to allow the skin to close safely
5. Subject is contraindicated for administration of nusinersen per its approved labeling
6. History of intrathecal granuloma formation
7. History of bacterial meningitis or aseptic meningitis within 6 months of screening
8. History of tumors or other spinal abnormalities documented by magnetic resonance imaging (MRI) or computed tomography (CT) that would interfere with the catheter implantation procedures or CSF circulation
9. History of hydrocephalus
10. Diagnosed degenerative muscular disease other than SMA
11. History of depression, cognitive impairment, or another psycho-behavioral problem that in the opinion of the Investigator may preclude safe participation in the clinical investigation and
12. Serious medical condition that, in the opinion of the investigator, may lead to reduced life expectancy beyond 12 months.
13. Subject is involved in another Investigation Device Exemption Study.

Where this trial is running

Phoenix, Arizona and 20 other locations

• Barrow Neurological Institute — Phoenix, Arizona, United States (Recruiting)
• Children's Hospital Orange County — Orange, California, United States (Recruiting)
• Stanford Medical Center — Palo Alto, California, United States (Recruiting)
• Rady Children's Hospital — San Diego, California, United States (Recruiting)
• Nemours Children's Hospital, Florida — Orlando, Florida, United States (Recruiting)
• Lurie Childrens Hospital — Chicago, Illinois, United States (Recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Helen DeVos Children's Hospital — Grand Rapids, Michigan, United States (Recruiting)
• Columbia University Irving Medical Center/NewYork Presbyterian Hospital — New York, New York, United States (Recruiting)
• UH Rainbow Babies and Children's Hospital — Cleveland, Ohio, United States (Recruiting)
• Penn State Milton S. Hershey Medical Center — Hershey, Pennsylvania, United States (Recruiting)
• Children's Hospital Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• Texas Children's Hospital — Houston, Texas, United States (Recruiting)
• University of Virginia — Charlottesville, Virginia, United States (Recruiting)
• Childrens Hospital of the King's Daughters — Norfolk, Virginia, United States (Recruiting)
• Universitätsklinikum Essen — Essen, Germany (Recruiting)
• Specialised Hospital Ludwika Rydygiera — Krakow, Poland (Recruiting)
• Research Institute of Polish Mother's Memorial Hospital — Lodz, Poland (Recruiting)
• Hospital Universitario La Paz — Madrid, Spain (Recruiting)
• Hospital Universitario y Politecnico la Fe de Valencia — Valencia, Spain (Recruiting)
• Sheffield Teaching Hospitals NHS Foundation Trust — Sheffield, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Janelle Arrambide

Conditions Spinal Muscular Atrophy; Spine Deformity; Scoliosis