遺伝子治療後の脊髄性筋萎縮症の小児参加者に対する早期介入として投与されたリスディプラムの有効性と安全性を評価する研究 (HINALEA 1)

Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled.

Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.

• RO7034067

The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.

The OrSAT is a validated assessment composed of a checklist of 12 questions assessing aspects of swallowing abilities thought to be clinically meaningful for a type 1 SMA population and developmentally appropriate for infants during the first months of life. Each item is graded with a score of 0 or 1, depending on the child's ability to perform the activity. As some items are age-dependent, the number of items to be used, and therefore the maximum score, changes with increasing age. In the infants younger than 6 months the maximum score is 7. For those between 6 and 9 months, maximum score is 10. For infants of 10 months or older, maximum total score is 12.

The p-FOIS is a 6-point scale that assesses feeding ability, 1= Nothing by mouth, 2= Tube dependent for all nutrition/hydration needs with minimal attempts at oral intake for experience and/or pleasure, 3= Tube dependent with consistent intake of food and/or fluid that meets some of the nutrition/hydration needs, 4= Total oral intake but special preparation required, e.g., thickened fluids, puréed diet (where not age-appropriate), 5= Total oral intake but requiring special conditions/modification, e.g., slow flow teat/side lying/pacing or specific food limitations, 6= Total, age-appropriate, oral intake with no restrictions. Higher score indicates higher level of function.

The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.

The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from <70 (impaired or delayed) to >129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills.

The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from <70 (impaired or delayed) to >129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills.

The WHO motor milestones evaluate gross motor development and comprise the time windows of achievement for six gross motor milestones based on data derived from the WHO Multicenter Growth Reference Study (MGRS). The six gross motor milestones are as follows: sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone. A yes response indicates that the participant reached a particular development milestone.

In a case of respiratory illness during the study, a range of clinical domain level items will be completed by the investigator, as needed. The CGI-C is a single item measure of change using seven response options: "Very much improved," "Much improved," "Minimally improved," "No change," "Minimally worse," "Much worse," and "Very much worse."