Spinal Muscular AtrophyPhase 4RISENCT05522361
Risdiplam in Patients With Spinal Muscular Atrophy Previously Treated With Nusinersen
A Phase 4 study testing Risdiplam in people with Spinal Muscular Atrophy, run by Clinic for Special Children at 1 site in United States.
Trial summary
Risdiplam Exchange (RISE) is a study of spinal muscular atrophy (SMA) patients who crossover to 36 months of open-label risdiplam monotherapy following a comparable period of nusinersen treatment. Read more about this study
- Who is it for?
- Ages 2 to 35 years
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- Risdiplam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Nov 2022to 15 Jun 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Biallelic SMN1 deletions
- 3 or 4 copies of SMN2
- Prior treatment with nusinersen for a minimum of 22 months
Who cannot join
- Prior treatment with SMN gene replacement therapy
- Prior exposure to another investigational agent.
- Confounding neuromuscular disorder other than SMA
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinic for Special Children
Strasburg, Pennsylvania, 17579
About this study
Official title: Risdiplam Exchange in Patients With Spinal Muscular Atrophy (SMA) Previously and Exclusively Treated With Nusinersen
Risdiplam Exchange (RISE) is a study of spinal muscular atrophy (SMA) patients who crossover to 36 months of open-label risdiplam monotherapy following a comparable period of nusinersen treatment. The schedule of assessments (SOAs) carry over seamlessly for the cohort from studies done while treated with nusinersen and continue to track the most informative outcomes from that trial (e.g. nine hole peg test and grip strength), while adding the Box and Block Test (BBT) as an additional measure of upper limb endurance and function.
Read the detailed description
Risdiplam is an orally bioavailable small molecule that distributes into the central nervous system (CNS) and peripheral tissues where it modifies SMN2 pre-mRNA splicing and increases tissue SMN protein levels. It was approved by the U.S. Food and Drug Administration for all SMA patients older than 2 months of age in August 2020.
Clinical trial data prompted us to consider risdiplam a reasonable alternative to nusinersen administered intrathecally or by subcutaneous intrathecal catheter (SIC) for patients with more advanced SMA. Considered within this clinical context, risdiplam presents a significant advantage by eliminating the risks of mechanical failure, intrathecal bleeding, and CNS infection associated with the SIC device. The schedule of assessments (SOAs) used in this cohort during the previous three-year period as part of a nusinersen study provide us with an established framework for data collection. Thus, the overall clinical experience with risdiplam as compared to nusinersen can be assessed using a prospective, crossover design in a real-world setting.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- Risdiplam
- Keywords
- nusinersen, prospective, risdiplam
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisdiplamDrug
administered to participants per product label insert
| Study group | Role | What they receive |
|---|---|---|
| Open-label crossover | Experimental | Participants crossover to 36 months of open-label risdiplam mono therapy following a comparable period of nusinersen treatment. Receives: Drug: Risdiplam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparative intrasubject performance on nine hole peg test (NHPT)
Time in seconds to place and subsequently remove nine one inch pegs in holes assessed in dominant and non dominant hands
Measured: 36 months
Secondary outcomes (5)
Intrasubject changes in lower limb and overall motor function
Revised Hammersmith Scale (RHS) of 33 items with grades of 0 (unable),1 (attempted, not completed) and 2 (achieves task); the greater the sum total, the higher overall motor function.
Measured: 36 months
Intrasubject changes in upper limb motor function
box and block test (BBT): number of 1 inch wood blocks moved from one compartment to an adjacent one over a wall within 5 minutes, with more blocks moved corresponding to higher upper limb motor function
Measured: 36 months
Intrasubject change in pulmonary function
maximal inspiratory pressure (MIP) and mean expiratory pressure (MEP), measured in centimeters of water displaced
Measured: 36 months
Frequency and type of adverse events
laboratory testing, self-reported, and observed during the study
Measured: 36 months
Comparative intrasubject change in grip strength
hand-held dynamometry (MyoGrip and MyoPinch) measures force in Newtons
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2022
- Study start6 Nov 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion15 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinic for Special Children
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Kevin A. Strauss, MD, Clinic for Special Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05522361
- Sponsor's protocol ID
- RISE
- Acronym
- RISE
- Status last verified
- Feb 2024
- First submitted
- 24 May 2022
- Last updated
- 7 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Strauss KA, Carson VJ, Brigatti KW, Young M, Robinson DL, Hendrickson C, Fox MD, Reed RM, Puffenberger EG, Mackenzie W, Miller F. Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy. J Pediatr Orthop. 2018 Nov/Dec;38(10):e610-e617. doi: 10.1097/BPO.0000000000001247.
PubMed 30134351Carson VJ, Young M, Brigatti KW, Robinson DL, Reed RM, Sohn J, Petrillo M, Farwell W, Miller F, Strauss KA. Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy. Muscle Nerve. 2022 Jan;65(1):51-59. doi: 10.1002/mus.27425. Epub 2021 Oct 19.
PubMed 34606118Ribero VA, Daigl M, Marti Y, Gorni K, Evans R, Scott DA, Mahajan A, Abrams KR, Hawkins N. How does risdiplam compare with other treatments for Types 1-3 spinal muscular atrophy: a systematic literature review and indirect treatment comparison. J Comp Eff Res. 2022 Apr;11(5):347-370. doi: 10.2217/cer-2021-0216. Epub 2022 Jan 18.
PubMed 35040693
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risdiplam Exchange in Patients With Spinal Muscular Atrophy (SMA) Previously and Exclusively Treated With Nusinersen
- ClinicalTrials.gov ID
- NCT05522361
- Acronym / sponsor ID
- RISE / RISE
- Conditions
- Spinal Muscular Atrophy
- Keywords
- nusinersen, prospective, risdiplam
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Clinic for Special ChildrenUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 6 Nov 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 15 Jun 2026 (estimated)
- First posted
- 31 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Risdiplam Exchange (RISE) is a study of spinal muscular atrophy (SMA) patients who crossover to 36 months of open-label risdiplam monotherapy following a comparable period of nusinersen treatment. The schedule of assessments (SOAs) carry over seamlessly for the cohort from studies done while treated with nusinersen and continue to track the most informative outcomes from that trial (e.g. nine hole peg test and grip strength), while adding the Box and Block Test (BBT) as an additional measure of upper limb endurance and function.
Detailed description
Risdiplam is an orally bioavailable small molecule that distributes into the central nervous system (CNS) and peripheral tissues where it modifies SMN2 pre-mRNA splicing and increases tissue SMN protein levels. It was approved by the U.S. Food and Drug Administration for all SMA patients older than 2 months of age in August 2020.
Clinical trial data prompted us to consider risdiplam a reasonable alternative to nusinersen administered intrathecally or by subcutaneous intrathecal catheter (SIC) for patients with more advanced SMA. Considered within this clinical context, risdiplam presents a significant advantage by eliminating the risks of mechanical failure, intrathecal bleeding, and CNS infection associated with the SIC device. The schedule of assessments (SOAs) used in this cohort during the previous three-year period as part of a nusinersen study provide us with an established framework for data collection. Thus, the overall clinical experience with risdiplam as compared to nusinersen can be assessed using a prospective, crossover design in a real-world setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-label crossover | Experimental | Drug: RisdiplamParticipants crossover to 36 months of open-label risdiplam mono therapy following a comparable period of nusinersen treatment. |
Who may qualify
- Ages
- 2 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Biallelic SMN1 deletions
- 3 or 4 copies of SMN2
- Prior treatment with nusinersen for a minimum of 22 months
Key exclusion criteria (3 listed)
- Prior treatment with SMN gene replacement therapy
- Prior exposure to another investigational agent.
- Confounding neuromuscular disorder other than SMA
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Risdiplamadministered to participants per product label insert | Drug | Open-label crossover |
Primary outcome
Comparative intrasubject performance on nine hole peg test (NHPT)
Time frame: 36 months
Time in seconds to place and subsequently remove nine one inch pegs in holes assessed in dominant and non dominant hands
5 secondary outcomes
Intrasubject changes in lower limb and overall motor function
Time frame: 36 months
Intrasubject changes in upper limb motor function
Time frame: 36 months
Intrasubject change in pulmonary function
Time frame: 36 months
Frequency and type of adverse events
Time frame: 36 months
Comparative intrasubject change in grip strength
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- Background: PubMed 30134351Strauss KA, Carson VJ, Brigatti KW, Young M, Robinson DL, Hendrickson C, Fox MD, Reed RM, Puffenberger EG, Mackenzie W, Miller F. Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy. J Pediatr Orthop. 2018 Nov/Dec;38(10):e610-e617. doi: 10.1097/BPO.0000000000001247.
- Background: PubMed 34606118Carson VJ, Young M, Brigatti KW, Robinson DL, Reed RM, Sohn J, Petrillo M, Farwell W, Miller F, Strauss KA. Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy. Muscle Nerve. 2022 Jan;65(1):51-59. doi: 10.1002/mus.27425. Epub 2021 Oct 19.
- Background: PubMed 35040693Ribero VA, Daigl M, Marti Y, Gorni K, Evans R, Scott DA, Mahajan A, Abrams KR, Hawkins N. How does risdiplam compare with other treatments for Types 1-3 spinal muscular atrophy: a systematic literature review and indirect treatment comparison. J Comp Eff Res. 2022 Apr;11(5):347-370. doi: 10.2217/cer-2021-0216. Epub 2022 Jan 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Risdiplam in people with Spinal Muscular Atrophy, run by Clinic for Special Children at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparative intrasubject performance on nine hole peg test (NHPT) (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05522361, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.