Spinal Muscular Atrophy
Conditions
Keywords
nusinersen, prospective, risdiplam
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.
Interventions
DRUGRisdiplam
administered to participants per product label insert
Sponsors
Genentech, Inc.
Clinic for Special Children
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparative intrasubject performance on nine hole peg test (NHPT) | 36 months | Time in seconds to place and subsequently remove nine one inch pegs in holes assessed in dominant and non dominant hands |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intrasubject changes in lower limb and overall motor function | 36 months | Revised Hammersmith Scale (RHS) of 33 items with grades of 0 (unable),1 (attempted, not completed) and 2 (achieves task); the greater the sum total, the higher overall motor function. |
| Intrasubject changes in upper limb motor function | 36 months | box and block test (BBT): number of 1 inch wood blocks moved from one compartment to an adjacent one over a wall within 5 minutes, with more blocks moved corresponding to higher upper limb motor function |
| Intrasubject change in pulmonary function | 36 months | maximal inspiratory pressure (MIP) and mean expiratory pressure (MEP), measured in centimeters of water displaced |
| Frequency and type of adverse events | 36 months | laboratory testing, self-reported, and observed during the study |
| Comparative intrasubject change in grip strength | 36 months | hand-held dynamometry (MyoGrip and MyoPinch) measures force in Newtons |
Countries
United States
Outcome results
None listed