Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)
- Conditions
- Spinal Muscular Atrophy
- Interventions
- Device: SMA-DAT Application and ADAM Sensor
- Registration Number
- NCT05232929
- Lead Sponsor
- Genentech, Inc.
- 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 SMA. In this study, participants will be followed for the duration of the study or until withdrawal of consent, loss to follow-up, or death. Participants who discontinue risdiplam may still remain in the study, if they agree to continue participating in the follow-up assessments.
An optional sub study will assess the feasibility, acceptability, and adherence of remote assessment of motor and bulbar functions in participants with SMA using wearable and smartphone-based biosensors. Approximately 39 participants from the main study are planned to be enrolled in the sub study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 402
- Clinical diagnosis of SMA
- Prescribed or continued risdiplam based on clinical judgment of prescriber, as per the Evrysdi® USPI, after U.S. FDA approval (07 August 2020)
Sub study:
Participants in the main study (ML43702) are eligible to be included in the sub study only if all of the following criteria apply:
- Age ≥ 10 years at the time of signing Informed Consent Form
- Willingness and ability to use smartphone technology
- Fluency in English (written and spoken as per the judgment of the investigator)
- Willingness and ability to complete all aspects of the sub study, including respiration and swallowing measurements using respiratory inductance plethysmography (RIP) belts and surface electromyography (sEMGs)
- Hammersmith Functional Motor Scale-Expanded (HFMSE) > 10
- Functional Oral Intake Scale (FOIS) >1
- Willingness to be video recorded during in-clinic SMA-DAT tasks and ADAM sensor assessments and training
- Availability of a caregiver who is willing to participate throughout this sub study
- Hypersensitivity to risdiplam
- Participated in a registrational trial for risdiplam (i.e., Firefish [NCT02913482], Sunfish [NCT02908685], Jewelfish [NCT03032172], and Rainbowfish [NCT03779334])
Sub study:
Potential participants will be excluded from the sub study if they meet any of the following criteria:
- Current respiratory infection that, in the opinion of the investigator, would interfere with the conduct of the sub study
- History or known presence of any significant psychiatric disorder such as schizophrenia, bipolar disorder, or substance use disorders
- Current active clinically significant anxiety or depressive disorder, as judged by the investigator, that is likely to impede a participant's ability to participate in the sub study
- Wearing a pacemaker (due to incompatibility with the ADAM sensor)
- Inability to tolerate the performance of sub study procedures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Risdiplam Risdiplam Participants who are taking risdiplam prescribed based on clinician judgment, as per the Evrysdi® USPI are enrolled in this arm. Substudy Cohort SMA-DAT Application and ADAM Sensor Participants from the main study will be enrolled in three sub-groups based on their Functional Oral Intake Scale (FOIS) score. Participants will be provided with a preconfigured study smartphone with the spinal muscular atrophy digital assessment tool (SMA-DAT) application and an ADvanced Acousto-Mechanic (ADAM) sensor. Participants will be asked to perform a programmed selection of SMA-DAT tasks for 24 days of the 27-day remote monitoring period.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) From enrollment up to the duration of the study or until withdrawal of consent, loss to follow-up, or death (up to approximately 4.5 years) An 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 AE 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 AE.
Sub study: Percentage of Participants Who Complete the Sub study Up to 9 Weeks Sub study: Percentage of Participants Who Provide at Least one day of In-clinic and at Least one day of Remote Monitoring Data Up to 9 Weeks Sub study: Number of Days of Passive Monitoring Data Collected Relative to the Total Number of Possible Passive Monitoring Days Up to 9 Weeks
- Secondary Outcome Measures
Name Time Method Sub study: Percentage of Participants Who Adhere to Remote Sensor-Based Assessments Up to 9 Weeks It is analysed as mean percentage of active task completed by participants out of the expected number of active tasks over the 27-day remote monitoring period.
Percentage of Participants Considered Improved on the Clinical Global Impression of Change (CGI-C) Scale From enrollment up to the duration of the study or until withdrawal of consent, loss to follow-up, or death (up to approximately 4.5 years) The 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" include responses of "very much improved, "much improved" and "minimally improved".
Sub study: Accuracy of ADAM Sensors in Detecting and Characterizing Bulbar Events (Swallowing and Respiration) Up to 9 Weeks The accuracy of the ADAM sensor in detecting and characterizing bulbar events (such as swallowing and respiration) will be assessed by measuring the concordance between sensor-based assessments and in-clinic assessments for these symptoms, and patient-reported outcomes.
Sub study: Median Satisfaction Scores From the Participant Satisfaction Questionnaire Day 29 At the end of the sub study visit, participants will fill out a satisfaction questionnaire to evaluate their overall experience with the SMA-DAT application and the and ADAM sensor used during the sub study. The questionnaire consists of 18 questions related to experience using the study smartphone, the ADAM sensor patch, and the SMA-DAT app during the last 29 days.
Sub study: Usability Ratings From the Participant Satisfaction Questionnaire Day 29 Usability of SMA-DAT will be directly evaluated using the subjective responses collected in the end-of-substudy visit satisfaction questionnaire. The questionnaire consists of 18 questions related to experience using the study smartphone and the SMA-DAT app during the last 29 days.
Sub study: Number of Participants With AE and SAE Related to the Sub study Procedures Up to 9 Weeks
Trial Locations
- Locations (39)
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Loma Linda University Health Care
🇺🇸Loma Linda, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Valley Children's Hospital
🇺🇸Madera, California, United States
University California - Irvine
🇺🇸Orange, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Medstar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Children's National Hospital
🇺🇸Washington, District of Columbia, United States
Nemour's Children's Hospital, Florida
🇺🇸Orlando, Florida, United States
All Children's Research Institute, Inc.
🇺🇸Saint Petersburg, Florida, United States
Advent Health Orlando
🇺🇸Winter Park, Florida, United States
Rare Disease Research, LLC
🇺🇸Atlanta, Georgia, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Pediatric Rehabilitation Center
🇺🇸Ann Arbor, Michigan, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Gillette Children's Specialty Healthcare
🇺🇸Minnetonka, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University;Wash Uni. Sch. Of Med
🇺🇸Saint Louis, Missouri, United States
NYU Hospital for Joint Diseases
🇺🇸New York, New York, United States
Columbia University Med Center
🇺🇸New York, New York, United States
Cincinnati Childrens Hospital
🇺🇸Cincinnati, Ohio, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Childrens Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas at Austin Health sciences, Dell Medical School
🇺🇸Austin, Texas, United States
Neurology & Neuromuscular Care Center
🇺🇸Denton, Texas, United States
Central Texas Neurology Consultants
🇺🇸Round Rock, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
University Of Utah
🇺🇸Salt Lake City, Utah, United States
University of Virginia Children?s Hospital
🇺🇸Charlottesville, Virginia, United States
MultiCare Health System Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
UBC (Remote Coordinating Center, no physical facility)
🇺🇸Morgantown, West Virginia, United States
Childrens Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Instituto de Rehabilitación del Caribe
🇵🇷Santurce, Puerto Rico