Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
An AE is any untoward medical occurrence in a 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, 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, or is a medically important event. |
Up to Day 1921 |
|
| Primary |
Change from Baseline in Growth Parameters |
Growth parameters will be assessed by measuring body length or height (if feasible and appropriate), ulnar length (all participants), and head circumference, chest circumference, and arm circumference (all participants 3 years of age and younger) in centimeters. |
Up to Day 1921 |
|
| Primary |
Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters |
|
Up to Day 1921 |
|
| Primary |
Number of Participants With Shifts from Baseline in Electrocardiogram (ECG) |
|
Up to Day 1921 |
|
| Primary |
Number of Participants With Shifts from Baseline in Vital Signs |
|
Up to Day 1921 |
|
| Primary |
Change from Baseline in Activated Partial Thromboplastin Time (aPTT) |
|
Up to Day 1921 |
|
| Primary |
Change from Baseline in Prothrombin Time (PT) |
|
Up to Day 1921 |
|
| Primary |
Change from Baseline in International Normalized Ratio (INR) |
|
Up to Day 1921 |
|
| Primary |
Change from Baseline in Urine Total Protein |
|
Up to Day 1921 |
|
| Primary |
Change from Baseline in Neurological Examination Outcomes for Participants =2 Years of Age |
For participants 2 years of age and younger, the Hammersmith Infant Neurological Exam (HINE) Sections 1 and 3 will be conducted. This standard examination (developed by [Dubowitz and Dubowitz 1981]) is a quantitative scorable method for assessing the neurological development of infants between 2 and 24 months of age. The examination includes assessment of cranial nerve functions, posture, movements, tone, and reflexes. The HINE Section 1 form utilized in ONWARD contains 26 items and the Section 3 form utilized contains 3 items. For HINE Section 1 items, each item is scored 0-3. For HINE Section 3 items, scoring is variable (1-4, 1-5, or 1-6). Higher scores indicate better neurological function. |
Up to Day 1921 |
|
| Primary |
Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age |
For all participants >2 years of age, standard neurological examinations, which include assessments of mental status, level of consciousness, sensory function, motor function, cranial nerve function, and reflexes, will be conducted. |
Up to Day 1921 |
|
| Primary |
Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements |
|
Up to Day 1921 |
|
| Primary |
Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec |
|
Up toDay 1921 |
|
| Secondary |
Total Number of New World Health Organization (WHO) Motor Milestones |
|
Up to Day 1921 |
|
| Secondary |
Number of Participants Who Used Respiratory Support, by Type |
|
Up to Day 1921 |
|
| Secondary |
Number of Hours Per Day of Respiratory Support |
|
Up to Day 1921 |
|
| Secondary |
Number of Days That Respiratory Support Is Used |
|
Up to Day 1921 |
|
| Secondary |
Time to Death (Overall Survival) |
|
Up to Day 1921 |
|
| Secondary |
Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score |
The CHOP INTEND test is designed to evaluate the motor skills of infants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4. The total score ranges from 0-64, with higher scores depicting better response. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566). |
Up to Day 1921 |
|
| Secondary |
Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones |
Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is the sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566). |
Up to Day 1921 |
|
| Secondary |
Percentage of HINE Section 2 Motor Milestone Responders |
Section 2 of HINE is used to assess motor milestones of participants. It is composed of 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. HINE section 2 motor milestone responder is participant who demonstrates at least 2-point increase in category of ability to kick or increase to maximal score on that category or 1-point increase in motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and among 7 motor milestone categories (excluding voluntary grasp), participant demonstrates improvement in more categories than worsening. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566). |
Up to Day 1921 |
|
| Secondary |
Percentage of Time Spent on Ventilation |
This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566). |
Up to Day 1921 |
|
| Secondary |
Time to Death or Permanent Ventilation |
Permanent ventilation is defined as tracheostomy or =16 hours of ventilation/day continuously for >21 days in the absence of an acute reversible event. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566). |
Up to Day 1921 |
|
| Secondary |
Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score |
The HFMSE is a tool used to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale (HFMS) was expanded to include 13 additional items to improve sensitivity for the higher functioning ambulant population. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all activities, with a maximum score of 66 with higher scores depicting better ability to perform activities. Participants = 2 years of age (at the time of the study visit) will be evaluated with HFMSE. |
Up to Day 1921 |
|
| Secondary |
Change from Baseline in Revised Upper Limb Module (RULM) Score |
The RULM is developed to assess upper limb functional abilities participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function. Participants = 2 years of age (at the time of the study visit) will be evaluated with RULM. |
Up to Day 1921 |
|
| Secondary |
Change From Baseline in Plasma Levels of Neurofilament (NF) |
|
Up to Day 1921 |
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