Long-Term Follow-Up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)
Study Details
Study Description
Brief Summary
A multi-center, longitudinal, prospective, non-comparative study to investigate the long-term safety and effectiveness of risdiplam, prescribed based on clinician judgment as per the Evrysdi® U.S. Package Insert (USPI) in adult and pediatric participants with spinal muscular atrophy (SMA). In this study, participants will be followed for up to 5 years from enrollment or until withdrawal of consent, loss to follow-up, or death.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Risdiplam Participants will receive risdiplam prescribed based on clinician judgment, as per the Evrysdi® USPI. |
Drug: Risdiplam
Participants will receive risdiplam orally.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) [Up to 5 years]
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events.
Secondary Outcome Measures
- Percentage of Participants Considered Improved on the Clinical Global Impression of Change (CGI-C) Scale [Up to 5 years]
The Clinical Global Impression of Change (CGI-C) is used to score a clinician's impression of a participant's change in global health. The CGI-C is a single item measure of change in global health, using seven response options: "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse". Participants considered as "improved" included responses of "very much improved, "much improved" and "minimally improved".
- Percentage of Infants Who Achieve the Attainment Levels of Six World Health Organization (WHO) Gross Motor Milestones [Up to 5 years]
Six distinct WHO gross motor milestones, which include sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone, and walking alone will be evaluated. Participants aged </=2 years will be evaluated.
- Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Score [Up to 5 years]
The CHOP-INTEND instrument was developed to evaluate motor function in infants with SMA. It consists of 16 items, where each item assesses a specific motor task graded on a scale of 0 to 4, where zero is no response and 4 is a complete response. The total score ranges from 0 to 64, with higher scores consistent with better motor function. A positive change from baseline indicates an improvement. Participants aged <2 years or participants >/=2 years who are not able to sit without support for at least 10 seconds as defined by the WHO ("non-sitters") will be evaluated.
- Change from Baseline in the Revised Upper Limb Module (RULM) Total Score [Up to 5 years]
The RULM is a 20 items scale that assesses the proximal and distal motor functions of the arm. There is an entry item, which does not contribute to the total score, 18 items are scored on a 3-point scale of 0 (unable), 1 (able, with modification), 2 (able, no difficulty) and 1 item is scored on a 2 point scale: 0 (unable) or 1 (able). The RULM total score is the sum of 19 items scores with a range of 0-37. Higher scores indicate greater upper limb function. A positive change from baseline indicates an improvement. Participants aged >/=2 years who are able to sit without support for at least 10 seconds as defined by the WHO but are not able to walk alone ("sitters") will be evaluated.
- Change from Baseline in Distance Walked During the Six-Minute Walk Test (6MWT) [Up to 5 years]
The 6MWT measures the distance a participant is able to walk in 6 minutes. Participants >/=3 years who are able to walk alone by taking at least 5 steps independently as defined by the WHO ("walkers") will be evaluated.
- Change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) [Up to 5 years]
HFMSE assesses motor function by functional item in order of progressive difficulty, with higher values showing higher function abilities. Each item is scored on a 3-point scale of 0 (unable), 1 (able, with modification), 2 (able, no difficulty). The total HFMSE score will be calculated as the sum of each item score with a range of 0-66 with a higher score indicating higher functional motor skills. A positive change from baseline indicates an improvement. Participants aged >/=2 years who are sitters or walkers will be evaluated.
- Change from Baseline in Motor Milestones Assessed in the Hammersmith Infant Neurological Examination Module 2 (HINE-2) [Up to 5 years]
The HINE is a standardized instrument that includes 26 items assessing different aspects of neurological examinations, such as cranial nerves, posture, movements, tone, and reflexes. In this study, Module 2 of the HINE (HINE-2) will be assessed. The HINE-2 evaluates 8 developmental milestones (head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing, and walking) scored on a 3, 4, or 5-point scale, with 0 indicating inability to perform a task and a score of 2, 3, or 4 (depending on the task) indicating full milestone development. The total score is calculated by summing the item scores to give a maximum possible score of 26. A higher score indicates higher motor skills. A positive change from baseline indicates an improvement. Participants aged <2 years will be evaluated.
- Percentage Change in Distance Walked in the First Versus the Last Minute of the 6MWT [Up to 5 years]
The 6MWT measures the distance a participant is able to walk in 6 minutes. The percent change in distance walked in the first versus the last minute of the test is used to evaluate the effectiveness of risdiplam on physiologic fatigue.
- Change From Baseline in Development of Scoliosis, Contractures, and Need for Surgical Treatment of Scoliosis [Up to 5 years]
- Time to Permanent Ventilation [Up to 5 years]
Permanent ventilation is defined as requiring a tracheostomy or more than 21 consecutive days of either non-invasive ventilation (>/=16 hours per day) or intubation, in the absence of an acute, reversible event. Participants aged <6 years will be evaluated.
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [Up to 5 years]
Forced expiratory volume (FEV1) is the volume forcefully exhaled in the first second of the forced vital capacity test. Participants aged >/=6 years will be evaluated.
- Change From Baseline in Forced Vital Capacity (FVC) [Up to 5 years]
Forced vital capacity (FVC) is the total volume that can be exhaled after inhaling maximally. Participants aged >/=6 years will be evaluated.
- Change From Baseline in Maximal Inspiratory Pressure (MIP) [Up to 5 years]
The maximal inspiratory pressure (MIP) is a non-invasive test of muscle strength, which measures the maximum strength of the diaphragm and other inspiratory muscles. Participants aged >/=6 years will be evaluated.
- Change From Baseline in Maximal Expiratory Pressure (MEP) [Up to 5 years]
The maximal expiratory pressure (MEP) is a non-invasive test of muscle strength, which measures the maximum strength of the abdominal muscles and other expiratory muscles. Participants aged >/=6 years will be evaluated.
- Change from Baseline in Best Sniff Nasal Inspiratory Pressure (SNIP) [Up to 5 years]
The Sniff Nasal Inspiratory Pressure (SNIP) is a volitional, non-invasive test of inspiratory muscle strength that has been successfully applied to children > 2 years of age. Participants aged >/=2 years will be evaluated.
- Change from Baseline Percentile for Weight-for-Age, Length/Height-for-Age, Weight-for-Length/Height, and Head Circumference-for-Age [Up to 5 years]
Participants aged <2 years will be evaluated.
- Change from Baseline in Chest Circumference [Up to 5 years]
Participants aged <2 years will be evaluated.
- Ratio Between Chest and Head Circumferences [Up to 5 years]
Participants aged <2 years will be evaluated.
- Time to Loss of Swallowing [Up to 5 years]
- Percentage of Participants Who Achieved or Maintain Ability to Feed Orally [Up to 5 years]
Feeding orally/eating function includes chewing, swallowing (exclusively or not); type of food intake, if available (solids, semi-solids, liquids).
- Percentage of Participants Who Achieved or Maintain Normal Crying Function and Speaking Function [Up to 5 years]
- Number of Participants Requiring Hospitalizations (For Any Reason) per Patient-Year [Up to 5 years]
- Average Length of Stay per Hospitalization [Up to 5 years]
- Participant Reported and Caregiver Reported Assessments Using SMA Independence Scale (SMAIS) - Upper Limb Module (ULM) and Ambulatory Module [Up to 5 years]
The SMAIS assesses the amount of assistance required from another individual to perform daily activities. ULM evaluation will be performed for sitters and ambulatory module will be performed for walkers. Participant-reported evaluations will be done in participants aged >/= 12 years. Caregiver-reported assessments will be performed for participants aged >/=2 years.
- Change in the Caregiver-Reported Function, as Measured by the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) [Up to 5 years]
Participants aged <21 years will be evaluated.
- Percentage of Participants With Treatment Discontinuation [Up to 5 years]
- Survival in Infants Aged < 2 Years With Type 1 SMA Over Time [Up to 5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed diagnosis of 5q-autosomal recessive SMA
-
Prescribed or continued risdiplam based on clinical judgment of prescriber, as per the Evrysdi® USPI, after U.S. FDA approval (07 August 2020)
Exclusion Criteria:
-
Hypersensitivity to risdiplam
-
Participated in a registrational trial for risdiplam (i.e., Firefish [NCT02913482], Sunfish [NCT02908685], Jewelfish [NCT03032172], and Rainbowfish [NCT03779334])
-
Aged >/=2 years with a score </=3 on the HFMSE or RULM at study entry
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72103 |
| 2 | University of Colorado; Anschutz Medical Campus Department of Neurology | Aurora | Colorado | United States | 80045 |
| 3 | Rare Disease Research, LLC | Atlanta | Georgia | United States | 30318 |
| 4 | Gillette Children's Specialty Healthcare | Minnetonka | Minnesota | United States | 55343 |
| 5 | Central Texas Neurology Consultants | Round Rock | Texas | United States | 78681 |
| 6 | University of Virginia Children's Hospital; Developmental | Charlottesville | Virginia | United States | 22903 |
| 7 | MultiCare Health System Institute for Research and Innovation | Tacoma | Washington | United States | 98405 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ML43702