Clinical trial NCT05522361: Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen
Official title: Risdiplam Exchange in Patients With Spinal Muscular Atrophy (SMA) Previously and Exclusively Treated With Nusinersen
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Spinal Muscular Atrophy
Keywords: nusinersen
prospective
risdiplam
Lead sponsor: Clinic for Special Children
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2022-08-31
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Risdiplam Exchange (RISE) is a study of spinal muscular atrophy (SMA) patients who crossover to 36 months of open-label risdiplam monotherapy following a comparable period of nusinersen treatment. The schedule of assessments (SOAs) carry over seamlessly for the cohort from studies done while treated with nusinersen and continue to track the most informative outcomes from that trial (e.g. nine hole peg test and grip strength), while adding the Box and Block Test (BBT) as an additional measure of upper limb endurance and function.

Detailed description: Risdiplam is an orally bioavailable small molecule that distributes into the central nervous system (CNS) and peripheral tissues where it modifies SMN2 pre-mRNA splicing and increases tissue SMN protein levels. It was approved by the U.S. Food and Drug Administration for all SMA patients older than 2 months of age in August 2020.

Clinical trial data prompted us to consider risdiplam a reasonable alternative to nusinersen administered intrathecally or by subcutaneous intrathecal catheter (SIC) for patients with more advanced SMA. Considered within this clinical context, risdiplam presents a significant advantage by eliminating the risks of mechanical failure, intrathecal bleeding, and CNS infection associated with the SIC device. The schedule of assessments (SOAs) used in this cohort during the previous three-year period as part of a nusinersen study provide us with an established framework for data collection. Thus, the overall clinical experience with risdiplam as compared to nusinersen can be assessed using a prospective, crossover design in a real-world setting.

Eligibility criteria: Inclusion Criteria:

* Biallelic SMN1 deletions
* 3 or 4 copies of SMN2
* Prior treatment with nusinersen for a minimum of 22 months

Exclusion Criteria:

* Prior treatment with SMN gene replacement therapy
* Prior exposure to another investigational agent.
* Confounding neuromuscular disorder other than SMA

Primary outcomes:
measure: Comparative intrasubject performance on nine hole peg test (NHPT)
timeFrame: 36 months
Secondary outcomes:
measure: Intrasubject changes in lower limb and overall motor function
timeFrame: 36 months
measure: Intrasubject changes in upper limb motor function
timeFrame: 36 months
measure: Intrasubject change in pulmonary function
timeFrame: 36 months
measure: Frequency and type of adverse events
timeFrame: 36 months
measure: Comparative intrasubject change in grip strength
timeFrame: 36 months
Other outcomes:
Locations:
city: Strasburg
country: United States
facility: Clinic for Special Children
state: Pennsylvania
Study officials:
References:
citation: Strauss KA, Carson VJ, Brigatti KW, Young M, Robinson DL, Hendrickson C, Fox MD, Reed RM, Puffenberger EG, Mackenzie W, Miller F. Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy. J Pediatr Orthop. 2018 Nov/Dec;38(10):e610-e617. doi: 10.1097/BPO.0000000000001247.
citation: Carson VJ, Young M, Brigatti KW, Robinson DL, Reed RM, Sohn J, Petrillo M, Farwell W, Miller F, Strauss KA. Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy. Muscle Nerve. 2022 Jan;65(1):51-59. doi: 10.1002/mus.27425. Epub 2021 Oct 19.
citation: Ribero VA, Daigl M, Marti Y, Gorni K, Evans R, Scott DA, Mahajan A, Abrams KR, Hawkins N. How does risdiplam compare with other treatments for Types 1-3 spinal muscular atrophy: a systematic literature review and indirect treatment comparison. J Comp Eff Res. 2022 Apr;11(5):347-370. doi: 10.2217/cer-2021-0216. Epub 2022 Jan 18.