Clinical trial NCT05232929: Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA)
Official title: Long-term Follow-up Study of Patients With Spinal Muscular Atrophy Receiving Risdiplam Treatment
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Spinal Muscular Atrophy
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 402
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Sub study: Percentage of Participants Who Complete the Sub study
timeFrame: Up to 9 Weeks
measure: Sub study: Percentage of Participants Who Provide at Least one day of In-clinic and at Least one day of Remote Monitoring Data
timeFrame: Up to 9 Weeks
measure: Sub study: Number of Days of Passive Monitoring Data Collected Relative to the Total Number of Possible Passive Monitoring Days
timeFrame: Up to 9 Weeks
Secondary outcomes:
measure: Percentage of Participants Considered Improved on the Clinical Global Impression of Change (CGI-C) Scale
timeFrame: 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)
measure: Sub study: Percentage of Participants Who Adhere to Remote Sensor-Based Assessments
timeFrame: Up to 9 Weeks
measure: Sub study: Accuracy of ADAM Sensors in Detecting and Characterizing Bulbar Events (Swallowing and Respiration)
timeFrame: Up to 9 Weeks
measure: Sub study: Median Satisfaction Scores From the Participant Satisfaction Questionnaire
timeFrame: Day 29
measure: Sub study: Usability Ratings From the Participant Satisfaction Questionnaire
timeFrame: Day 29
measure: Sub study: Number of Participants With AE and SAE Related to the Sub study Procedures
timeFrame: Up to 9 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Health Care
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Orange
country: United States
facility: University California - Irvine
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Orlando
country: United States
facility: Nemour's Children's Hospital, Florida
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Research Institute, Inc.
state: Florida
city: Winter Park
country: United States
facility: Advent Health Orlando
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Pediatric Rehabilitation Center
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Minnetonka
country: United States
facility: Gillette Children's Specialty Healthcare
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University;Wash Uni. Sch. Of Med
state: Missouri
city: New York
country: United States
facility: NYU Hospital for Joint Diseases
state: New York
city: New York
country: United States
facility: Columbia University Med Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Austin
country: United States
facility: University of Texas at Austin Health sciences, Dell Medical School
state: Texas
city: Denton
country: United States
facility: Neurology & Neuromuscular Care Center
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Children?s Hospital
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Morgantown
country: United States
facility: UBC (Remote Coordinating Center, no physical facility)
state: West Virginia
city: Milwaukee
country: United States
facility: Childrens Hospital of Wisconsin
state: Wisconsin
city: Santurce
country: Puerto Rico
facility: Instituto de Rehabilitación del Caribe
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: