Back to resultsA Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam (ASCEND)
Primary Purpose
Spinal Muscular Atrophy
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Nusinersen
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Muscular Atrophy
Eligibility Criteria
Key Inclusion Criteria:
- Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
- Diagnosis of later-onset SMA with symptom onset at age >6 months.
- Aged ≥15 to ≤50 years at the time of informed consent
- Body weight >20 kg.
Received oral risdiplam per the approved label or per the managed access program as follows
- Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment.
- Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment.
- Able to perform the age-appropriate functional assessments in the study.
- RULM entry item A score ≥3.
- RULM total score ≥5 and ≤30 at Screening.
- Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
- Willing to stop risdiplam treatment.
- Willing and able to start treatment with HD nusinersen.
Key Exclusion Criteria:
- Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration.
- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
- Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
- Permanent tracheostomy or permanent ventilation at Screening.
- The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening.
- History of bacterial meningitis, viral encephalitis, or hydrocephalus.
- Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
- Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
- Treatment with an investigational drug, biological agent, or device within 30 days or 5 halflives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Barrow Neurological Institute
- Arkansas Children's HospitalRecruiting
- Stanford Neuromuscular Research Office (Research Coordinator Office)Recruiting
- Georgetown University
- Rare Disease Research InstituteRecruiting
- Ann & Robert H. Lurie Children's Hospital of ChicagoRecruiting
- University of Iowa Children's HospitalRecruiting
- Boston Children's HospitalRecruiting
- Memorial Healthcare
- Columbia UniversityRecruiting
- Wake Forest University - School of Medicine - CentralRecruiting
- The Ohio State
- University of PennsylvaniaRecruiting
- The University of Texas Health Science Center at HoustonRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- University of Wisconsin
- UZ GentRecruiting
- UZ Leuven
- Hospital de Clínicas de Porto AlegreRecruiting
- Hospital das Clinicas - FMUSPRecruiting
- Universitaetsklinikum HeidelbergRecruiting
- Universitaetsklinikum Giessen und Marburg GmbHRecruiting
- Universitaetsklinikum EssenRecruiting
- Fondazione Serena Onlus - Centro Clinico NemoRecruiting
- Ospedale Pediatrico Bambino Gesù
- Fondazione IRCCS Istituto Neurologico Carlo BestaRecruiting
- Instytut Centrum Zdrowia Matki PolkiRecruiting
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we WroclawiuRecruiting
- Szpital Specjalistyczny im. L.Rydygiera w KrakowieRecruiting
- Samodzielny Publiczny Centralny Szpital Kliniczny
- Hospital Sant Joan de DeuRecruiting
- Hospital Universitari i Politecnic La FeRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Higher Dose Nusinersen
Arm Description
There will be two groups of participants previously treated with risdiplam in the study (nusinersen-naive group and nusinersen-experienced group), who will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months.
Outcomes
Primary Outcome Measures
Change in Total Revised Upper Limb Module (RULM) Score
The RULM is being utilized to assess upper limb functional abilities of 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.
Secondary Outcome Measures
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 that does not necessarily have a causal relationship with the 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 or 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.
Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05067790
Brief Title
A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam
Acronym
ASCEND
Official Title
A Phase 3b Study to Evaluate Higher Dose Nusinersen (BIIB058) in Patients With Spinal Muscular Atrophy Previously Treated With Risdiplam
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 21, 2022 (Actual)
Primary Completion Date
June 14, 2027 (Anticipated)
Study Completion Date
June 14, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to evaluate motor function following treatment with HD nusinersen in participants with spinal muscular atrophy (SMA) previously treated with risdiplam.
The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Muscular Atrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
135 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Higher Dose Nusinersen
Arm Type
Experimental
Arm Description
There will be two groups of participants previously treated with risdiplam in the study (nusinersen-naive group and nusinersen-experienced group), who will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months.
Intervention Type
Drug
Intervention Name(s)
Nusinersen
Other Intervention Name(s)
BIIB058, Spinraza
Intervention Description
Administered as specified in the treatment arm
Primary Outcome Measure Information:
Title
Change in Total Revised Upper Limb Module (RULM) Score
Description
The RULM is being utilized to assess upper limb functional abilities of 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.
Time Frame
Up to Day 855
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the 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 or 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.
Time Frame
Up to Day 855
Title
Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline
Time Frame
Up to Day 855
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
Diagnosis of later-onset SMA with symptom onset at age >6 months.
Aged ≥15 to ≤50 years at the time of informed consent
Body weight >20 kg.
Received oral risdiplam per the approved label or per the managed access program as follows
Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment.
Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment.
Able to perform the age-appropriate functional assessments in the study.
RULM entry item A score ≥3.
RULM total score ≥5 and ≤30 at Screening.
Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
Willing to stop risdiplam treatment.
Willing and able to start treatment with HD nusinersen.
Key Exclusion Criteria:
Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration.
Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
Permanent tracheostomy or permanent ventilation at Screening.
The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening.
History of bacterial meningitis, viral encephalitis, or hydrocephalus.
Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
Treatment with an investigational drug, biological agent, or device within 30 days or 5 halflives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US Biogen Clinical Trial Center
Phone
866-633-4636
Email
clinicaltrials@biogen.com
First Name & Middle Initial & Last Name or Official Title & Degree
Global Biogen Clinical Trial Center
Email
clinicaltrials@biogen.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shafeeq Ladha
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kapril Arya, MD
Phone
501-364-1850
Email
karya@uams.edu
First Name & Middle Initial & Last Name & Degree
Ashley Bryan
Phone
501-364-3122
Email
bryanar@archildrens.org
First Name & Middle Initial & Last Name & Degree
Kapil Arya, MD
Facility Name
Stanford Neuromuscular Research Office (Research Coordinator Office)
City
San Carlos
State/Province
California
ZIP/Postal Code
94070
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
650-725-7622
First Name & Middle Initial & Last Name & Degree
John Day
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shakti Nayar
Facility Name
Rare Disease Research Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Han Phan, MD
Phone
678-883-6897
Email
hphan@rarediseaseresearh.com
First Name & Middle Initial & Last Name & Degree
Kallie Platt
Phone
678-883-6897
Email
kallie.platt@rarediseaseresearch.com
First Name & Middle Initial & Last Name & Degree
Han Phan, MD
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2605
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
312-227-3550
First Name & Middle Initial & Last Name & Degree
Nancy Kuntz
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
319-356-1851
First Name & Middle Initial & Last Name & Degree
Katherine Mathews
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
617-355-8036
First Name & Middle Initial & Last Name & Degree
Basil Darras
Facility Name
Memorial Healthcare
City
Owosso
State/Province
Michigan
ZIP/Postal Code
48867
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret Frey
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
212-305-8549
First Name & Middle Initial & Last Name & Degree
Claudia Chiriboga
Facility Name
Wake Forest University - School of Medicine - Central
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1078
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
336-716-4101
Email
sdharris@wakehealth.edu
First Name & Middle Initial & Last Name & Degree
Michael Cartwright, MD, MS
Facility Name
The Ohio State
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bakri Elsheikh
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
215-662-4000
First Name & Middle Initial & Last Name & Degree
Lauren Elman
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
713-500-7101
First Name & Middle Initial & Last Name & Degree
Shade Moody
Facility Name
Children's Hospital of The King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
757-668-5755
Email
proud.research@chkd.org
First Name & Middle Initial & Last Name & Degree
Crystal Proud, MD
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Kwon
Facility Name
UZ Gent
City
Gent
State/Province
C Heymanslaan 10
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
Phone
+3293321954
First Name & Middle Initial & Last Name & Degree
Nicolas Deconinck
Facility Name
UZ Leuven
City
Leuven
State/Province
Herestraat 49
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
Phone
+555133598012
First Name & Middle Initial & Last Name & Degree
Jonas Alex Morales Saute
Facility Name
Hospital das Clinicas - FMUSP
City
Sao Paulo
ZIP/Postal Code
05403900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
Phone
+5511975157219
First Name & Middle Initial & Last Name & Degree
Edmar Zanoteli
Facility Name
Universitaetsklinikum Heidelberg
City
Heidelberg
State/Province
Baden Wuerttemberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Phone
+496221567075
First Name & Middle Initial & Last Name & Degree
Weiler Markus
Facility Name
Universitaetsklinikum Giessen und Marburg GmbH
City
Rudolf-Buchheim Street 8
State/Province
Giessen
ZIP/Postal Code
35392
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Phone
+4964198543481
First Name & Middle Initial & Last Name & Degree
Andreas Hahn
Facility Name
Universitaetsklinikum Essen
City
Essen
State/Province
Nordrhein Westfalen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
Phone
+4964198543481
First Name & Middle Initial & Last Name & Degree
Tim Hagenacker
Facility Name
Fondazione Serena Onlus - Centro Clinico Nemo
City
Milan
State/Province
Milano
ZIP/Postal Code
20162
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
Phone
+393495607450
First Name & Middle Initial & Last Name & Degree
Valeria Sansone
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Rome
State/Province
Roma
ZIP/Postal Code
00165
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edmar Zanoteli
Facility Name
Fondazione IRCCS Istituto Neurologico Carlo Besta
City
Milano
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
Phone
+39223942217
First Name & Middle Initial & Last Name & Degree
Riccardo Masson
Facility Name
Instytut Centrum Zdrowia Matki Polki
City
Lodz
State/Province
Lodzkie
ZIP/Postal Code
93-338
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
Phone
+48606989185
First Name & Middle Initial & Last Name & Degree
Lukasz Przyslo
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
City
Borowska
State/Province
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
Phone
+48717343100
First Name & Middle Initial & Last Name & Degree
Magdalena Koszewicz
Facility Name
Szpital Specjalistyczny im. L.Rydygiera w Krakowie
City
Krakow
ZIP/Postal Code
31-637
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
Phone
+48604565621
First Name & Middle Initial & Last Name & Degree
Ryszard Nowak
Facility Name
Samodzielny Publiczny Centralny Szpital Kliniczny
City
Warszawa
ZIP/Postal Code
02-091
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Kostera Pruszczyk
Facility Name
Hospital Sant Joan de Deu
City
Esplugues de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
Phone
+34936009733
First Name & Middle Initial & Last Name & Degree
Andres Nascimento Osorio
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
Phone
+34687450013
First Name & Middle Initial & Last Name & Degree
Inmaculada Pitarch Castellano
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Links:
URL
https://www.ascendsmastudy.com/
Description
Disclaimer: Residents in the United States may click here to find out more about participation in this trial.
Learn more about this trial
A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam
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