Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen (RISE)

Clinic for Special Children

Status and phase: Active, not recruiting; Phase 4

Conditions: Spinal Muscular Atrophy

Treatments: Drug: Risdiplam

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05522361

RISE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 estimated patients

Sex: All

Ages: 2 to 35 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Open-label crossover

Experimental group

Description:

Participants crossover to 36 months of open-label risdiplam mono therapy following a comparable period of nusinersen treatment.

Treatment:

Drug: Risdiplam