Study of Nusinersen Among Patients with Spinal Muscular Atrophy Who Received Onasemnogene Abeparvovec

JRCT ID: jRCT2051210186

Registered date:03/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Spinal muscular atrophy (SMA)
• Date of first enrollment: 31/03/2022
• Target sample size: 60
• Countries of recruitment: United States,Japan,Italy,Japan,Spain,Japan,Israel,Japan,Germany,Japan
• Study type: Interventional

Intervention(s)

Research Name: BIIB058
Generic Name: Nusinersen
Trade Name: Spinraza
Participants will undergo a loading period during which they will receive 12 mg nusinersen administered IT on Days 1,15, 29, and 64, followed by a maintenance period during which the participants will receive 12 mg nusinersen IT every 4 months.

Outcome(s)

Primary Outcome

- Total HINE Section 2 motor milestones score
Section 2 of the HINE is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking.

Secondary Outcome

- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs).
An AE is any untoward medical occurrence in a patient or clinical investigation subject (participant) administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
An SAE is any untoward medical occurrence that at any dose:
- Results in death
- In the view of the Investigator, places the participant at immediate risk of death.
- Requires inpatient hospitalization or prolongation of existing hospitalization
- Results in persistent or significant disability/incapacity
- Results in a birth defect
- Is a medically important event

- Change from baseline in clinical laboratory parameters, ECGs, and vital sign

- WHO motor milestones

- Change from baseline in applicable motor function assessments: CHOP INTEND, HFMSE, and RULM
The CHOP INTEND test was designed to evaluate the motor skills of infants with significant motor weakness, including infants with SMA. The CHOP INTEND test captures neck, trunk, and proximal and distal limb strength in 14 elicited and 2 observational items.
The HFMSE is a reliable and validated tool used to assess motor function in children with SMA.
The scale was originally developed with 20 scored activities and was devised for use in children with Type II and Type III SMA with limited ambulation to give objective information on motor ability and clinical progression.
The RULM is an outcome measure developed to assess upper limb functional abilities in patients with SMA. This test consists of upper limb performance items that are reflective of activities of daily living.

- Time to death or permanent ventilation (tracheostomy or >= 16 hours ventilation/day continuously for > 21 days in the absence of an acute reversible event)

Key inclusion & exclusion criteria

• Age minimum: >= 2month old
• Age maximum: <= 36month old
• Gender: Both

Include criteria

- Genetic documentation of 5q SMA homozygous SMN1 gene deletion or mutation or compound heterozygous mutation.

- Must have received onasemnogene abeparvovec.

- Suboptimal clinical status as determined by the Investigator.

Exclude criteria

- Severe or serious AEs related to onasemnogene abeparvovec therapy that were ongoing.

- Prior exposure to nusinersen.

Related Information

• Primary Sponsor: Toda Yasuo
• Secondary ID(s): NCT04488133