Overview
The primary objective of the clinical investigation is to demonstrate successful clinical use of the ThecaFlex DRx™ System in delivering nusinersen in subjects with spinal muscular atrophy (SMA).
All enrolled subjects will undergo implantation of the investigational device (ThecaFlex DRx™ System) and will be followed for 12 months after receiving the implant. The 12-month data will be used to assess the primary endpoint support a Pre-Market Approval (PMA) application.
Description
This is a multicenter, multi-national, prospective, non-randomized, single arm, group sequential design, pivotal clinical investigation (device exemption study) to assess the safety and performance of the ThecaFlex DRx™ System in subjects with SMA.
The subject population will include subjects aged ≥ 3 years with SMA who are considered candidates for intrathecal port and catheter implantation because they require chronic, bolus intrathecal administration of necessary therapy, and who meet all the inclusion/exclusion criteria for the clinical investigation.
After a screening period of up to 30 days, all enrolled subjects will undergo implantation of the investigational device (ThecaFlex DRx™ System) and will be followed for 12 months after receiving the implant.
In agreement with the nusinersen dosing information, the treatment frequency will be adapted for non-naïve and naïve subjects:
Subjects who are not naïve to nusinersen should have nusinersen maintenance doses administered via the implant every 4 months (i.e., 4, 8, and 12 months after their last nusinersen dose, before enrollment in the clinical investigation).
Subjects who are naïve to nusinersen will have their first three loading doses administered via the implant at 14-day intervals. The fourth loading dose should be administered 30 days after the third dose. A maintenance dose should be administered once every 4 months thereafter within the 12 months post-implantation.
A DMC and Clinical Events Committee (CEC), independent of each other and the Sponsor, will be used to perform ongoing consistent adjudication of events related to the safety throughout the entire duration of the clinical investigation and to periodically review data that relate to the safety of the study.
The clinical investigation will enroll 90 subjects. The clinical investigation incorporates a lead-in phase which consists of 10 subjects enrolled, implanted, and followed for 30-days. Enrollment for the lead-in phase is expected to take approximately 6 to 9 months, at which point the Data Monitoring Committee (DMC) will review the data for safety and approve continuation of enrollment. The second phase of enrollment is expected to take approximately 12 to 15 months.
Individual subjects are anticipated to be enrolled in the clinical investigation for approximately 37 months. The total duration of this clinical investigation is estimated to be approximately 60 months.
Eligibility
Inclusion Criteria:
- Subject is 3 years or older
- Subject diagnosed with SMA who are candidates for Spinraza treatment as indicated in its label
- Subject resistant to lumbar puncture (LP), where resistance is defined as:
- 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
- Subjects for whom the treating physician determines implantation of the ThecaFlex DRx™ System is otherwise in the subject's best interest
- 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
- 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
- Subject (or subject's legally authorized representative) is willing and able to provide written informed consent; and
- Subject and parent/caregiver able and willing to complete all clinical investigation procedures, measurements, and visits.
Exclusion Criteria:
- Subject meets any of the contraindications for use of the ThecaFlex DRx™ System as outlined in the ThecaFlex DRx™ System Instructions for Use
- 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)
- Subject is pregnant or nursing or plans to become pregnant during the course of the clinical investigation
- 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:
- Severe structural impediment that may preclude safe implantation of the catheter and port
- Major medical events within 60 days prior to screening; or
- Relevant surgeries (e.g., head and neck, back, etc.) within 60 days prior to screening or planned during the duration of the clinical investigation
- Space-occupying lesion with mass effect
- Posterior fossa mass
- Arnold-Chiari malformation
- Coagulation abnormalities and/or thrombocytopenia
- Insufficient or inadequate skin or underlying fat to adequately protect the port or enough surface area to allow the skin to close safely
- Subject is contraindicated for administration of nusinersen per its approved
labeling
- History of intrathecal granuloma formation
- History of bacterial meningitis or aseptic meningitis within 6 months of screening
- 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
- History of hydrocephalus
- Diagnosed degenerative muscular disease other than SMA
- 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
- Serious medical condition that, in the opinion of the investigator, may lead to reduced life expectancy beyond 12 months.
- Subject is involved in another Investigation Device Exemption Study.