Back to resultsA Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies (SHINE)
Primary Purpose
Spinal Muscular Atrophy
Status
Completed
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 focused on measuring SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443, SHINE, IONIS-SMNRx, IONIS-SMN Rx, Spinraza, nusinersen
Eligibility Criteria
Key Inclusion Criteria:
- Signed informed consent of parent or guardian and signed informed assent of participant, if indicated per participant's age and institutional guidelines.
- Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks
Key Exclusion Criteria:
- Have any condition or worsening condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
- Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
- Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
- Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- David Geffen School of Medicine at UCLA
- Stanford University School of Medicine
- Children's Hospital Colorado
- Connecticut Children's Medical Center
- Nemours Children's Clinic
- Ann & Robert H. Lurie Children's Hospital of Chicago
- The Johns Hopkins Hospital
- Boston Children's Hospital
- Gillette Children's Specialty Healthcare
- Washington University School of Medicine
- Columbia University Medical Center
- Duke University School of Medicine
- Duke University School of Medicine
- Oregon Health Sciences University
- Children's Hospital of Philadelphia
- Children's Medical Center
- University of Utah
- Seattle Children's Hospital
- Sydney Children's Hospital Clinical Research Centre
- Royal Children's Hospital
- Universitair Kinderziekenhuis Koningin Fabiola
- BC Children's Hospital / UBC
- Children's Health Research Institute
- McGill University Health Centre
- Armand Trousseau Hospital, I-Motion
- LMU-Campus Innenstadt
- Universitatsklinikum Essen
- Universitaetsklinikum Freiburg
- The University of Hong Kong
- Pediatric Neurology Unit, Catholic University
- Istituto Giannina Gaslini, Centro Traslazionale di Miologia
- Department of Neuroscience, Università di Messina, AOU Polic
- Aichi Children's Health and Medical Center
- Hyogo College of Medicine
- Tokyo Women's Medical University
- Kumamoto University Hospital
- Miyagi Prefectural Children Hospital
- University of Miyazaki Hospital
- Seoul National University Hospital
- Hospital Sant Joan de Deu
- Hospital Universitario Vall de Hebron
- Hospital Universitario La Paz
- The Queen Silvia Children's Hospital
- Uníversity of Hacettepe
- Marmara University Pendik Training and Research Hospital
- MRC Centre for Neuromuscular Diseases at Newcastle
- UCL Institute of Child Health
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1
Group 2
Group 3
Group 4
Group 5
Arm Description
Participants transitioned from ISIS 396443-CS3B (NCT02193074)
Participants transitioned from ISIS 396443-CS4 (NCT02292537)
Participants transitioned from ISIS 396443-CS12 (NCT02052791)
Participants transitioned from ISIS 396443-CS3A (NCT01839656)
Participants transitioned from 232SM202 (NCT02462759)
Outcomes
Primary Outcome Measures
Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs)
Number of participants with clinically significant vital sign abnormalities
Number of participants with clinically significant weight abnormalities
Number of participants with clinically significant neurological examination abnormalities
Number of participants with clinically significant laboratory assessment abnormalities
Number of participants with clinically significant coagulation parameter abnormalities
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
Change from Baseline in concomitant medications
Secondary Outcome Measures
Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)
Time to death or permanent ventilation
Percentage of participants not requiring permanent ventilation
Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.
Change from Baseline in Hammersmith Functional Motor Scale
The HFMSE tests motor function of participants with SMA. The original 20 item Hammersmith Functional Motor Scale was expanded to include 13 additional adapted items from the Gross Motor Function Measure to improve sensitivity for the higher functioning ambulant population.
Change from Baseline in Revised Upper Limb Module (RULM)
Change from Baseline in 6-Minute Walk Test (6MWT)
6MWT: walking up and down a 25 meter track without aids or orthotics as fast as possible for 6 minutes. Lap splits, minute splits and total distance are recorded, in addition to any rests and falls.
Change from Baseline in Compound Muscular Action Potential (CMAP)
CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles.
Change from Baseline in body length and/or height (for all participants)
Change from Baseline in head circumference (for participants up to 36 months of age)
Change from Baseline in chest circumference (for participants up to 36 months of age)
Change from Baseline in arm circumference (for participants up to 36 months of age)
Proportion of CMAP responders
Number of participants with motor milestones achieved
Proportion of participants who achieved standing alone
Proportion of participants who achieved walking with assistance
Number of participants with serious respiratory events
Number of participants hospitalized
Duration of hospitalizations
Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine
Change from Baseline in Quality of Life (QOL) Questionnaires
Number of Disease-related hospitalizations and AEs
Overall survival rate
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02594124
Brief Title
A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
Acronym
SHINE
Official Title
An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 4, 2015 (Actual)
Primary Completion Date
August 29, 2023 (Actual)
Study Completion Date
August 29, 2023 (Actual)
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
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective is to evaluate the long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to participants with Spinal Muscular Atrophy (SMA) who previously participated in investigational studies of nusinersen. The secondary objective is to examine the long-term efficacy of nusinersen administered by IT injection to participants with SMA who previously participated in investigational studies of nusinersen.
Detailed Description
This study was initiated and the protocol was registered by Ionis Pharmaceuticals, Inc.
In August 2016, Biogen assumed responsibility for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Muscular Atrophy
Keywords
SMA, SMN, SMNRx, ISIS-SMNRx, ISIS 396443, SHINE, IONIS-SMNRx, IONIS-SMN Rx, Spinraza, nusinersen
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
During the blinded loading period, the following participants will be masked:
Key site personnel (Investigator, Study Coordinator, and Outcomes Assessors)
Participant
The sponsor
After the loading period has been completed, subsequent doses will be unblinded.
Allocation
Non-Randomized
Enrollment
292 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Participants transitioned from ISIS 396443-CS3B (NCT02193074)
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Participants transitioned from ISIS 396443-CS4 (NCT02292537)
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Participants transitioned from ISIS 396443-CS12 (NCT02052791)
Arm Title
Group 4
Arm Type
Experimental
Arm Description
Participants transitioned from ISIS 396443-CS3A (NCT01839656)
Arm Title
Group 5
Arm Type
Experimental
Arm Description
Participants transitioned from 232SM202 (NCT02462759)
Intervention Type
Drug
Intervention Name(s)
nusinersen
Other Intervention Name(s)
ISIS 396443, Spinraza, BIIB058, IONIS SMN Rx, ISIS SMNRx
Intervention Description
Administered by intrathecal (IT) injection
Primary Outcome Measure Information:
Title
Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs)
Time Frame
Up to Day 1814
Title
Number of participants with clinically significant vital sign abnormalities
Time Frame
Up to Day 1814
Title
Number of participants with clinically significant weight abnormalities
Time Frame
Up to Day 1814
Title
Number of participants with clinically significant neurological examination abnormalities
Time Frame
Up to Day 1814
Title
Number of participants with clinically significant laboratory assessment abnormalities
Time Frame
Up to Day 1814
Title
Number of participants with clinically significant coagulation parameter abnormalities
Time Frame
Up to Day 1814
Title
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
Time Frame
Up to Day 1814
Title
Change from Baseline in concomitant medications
Time Frame
Up to Day 1814
Secondary Outcome Measure Information:
Title
Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
Time Frame
Up to Day 1814
Title
Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)
Time Frame
Up to Day 1814
Title
Time to death or permanent ventilation
Time Frame
Up to Day 1814
Title
Percentage of participants not requiring permanent ventilation
Time Frame
Up to Day 1814
Title
Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
Description
CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.
Time Frame
Up to Day 1814
Title
Change from Baseline in Hammersmith Functional Motor Scale
Description
The HFMSE tests motor function of participants with SMA. The original 20 item Hammersmith Functional Motor Scale was expanded to include 13 additional adapted items from the Gross Motor Function Measure to improve sensitivity for the higher functioning ambulant population.
Time Frame
Up to Day 1814
Title
Change from Baseline in Revised Upper Limb Module (RULM)
Time Frame
Up to Day 1814
Title
Change from Baseline in 6-Minute Walk Test (6MWT)
Description
6MWT: walking up and down a 25 meter track without aids or orthotics as fast as possible for 6 minutes. Lap splits, minute splits and total distance are recorded, in addition to any rests and falls.
Time Frame
Up to Day 1814
Title
Change from Baseline in Compound Muscular Action Potential (CMAP)
Description
CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles.
Time Frame
Up to Day 1814
Title
Change from Baseline in body length and/or height (for all participants)
Time Frame
Up to Day 1814
Title
Change from Baseline in head circumference (for participants up to 36 months of age)
Time Frame
Up to Day 1814
Title
Change from Baseline in chest circumference (for participants up to 36 months of age)
Time Frame
Up to Day 1814
Title
Change from Baseline in arm circumference (for participants up to 36 months of age)
Time Frame
Up to Day 1814
Title
Proportion of CMAP responders
Time Frame
Up to Day 1814
Title
Number of participants with motor milestones achieved
Time Frame
Up to Day 1814
Title
Proportion of participants who achieved standing alone
Time Frame
Up to Day 1814
Title
Proportion of participants who achieved walking with assistance
Time Frame
Up to Day 1814
Title
Number of participants with serious respiratory events
Time Frame
Up to Day 1814
Title
Number of participants hospitalized
Time Frame
Up to Day 1814
Title
Duration of hospitalizations
Time Frame
Up to Day 1814
Title
Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine
Time Frame
Up to Day 1814
Title
Change from Baseline in Quality of Life (QOL) Questionnaires
Time Frame
Up to Day 1814
Title
Number of Disease-related hospitalizations and AEs
Time Frame
Up to Day 1814
Title
Overall survival rate
Time Frame
Up to Day 1814
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Signed informed consent of parent or guardian and signed informed assent of participant, if indicated per participant's age and institutional guidelines.
Completion of the index study in accordance with the study protocol or as a result of Sponsor decision (e.g., early termination of the index study) within the preceding 16 weeks
Key Exclusion Criteria:
Have any condition or worsening condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study
Clinically significant abnormalities in hematology or clinical chemistry parameters or electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
Participant's parent or legal guardian is not willing or able to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study
Treatment with another investigational agent, biological agent, or device within one month of Screening, or 5 half-lives of study agent, whichever is longer
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-8344
Country
United States
Facility Name
Stanford University School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Nemours Children's Clinic
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
New York
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
The Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Gillette Children's Specialty Healthcare
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University School of Medicine
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke University School of Medicine
City
Miyagi
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oregon Health Sciences University
City
Durham
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Utah
City
Obu, Aichi
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Sydney Children's Hospital Clinical Research Centre
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Universitair Kinderziekenhuis Koningin Fabiola
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
BC Children's Hospital / UBC
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
Children's Health Research Institute
City
Brussel
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Armand Trousseau Hospital, I-Motion
City
Paris
State/Province
Paris 9
ZIP/Postal Code
75012
Country
France
Facility Name
LMU-Campus Innenstadt
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
80337
Country
Germany
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitaetsklinikum Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
The University of Hong Kong
City
Hong Kong
State/Province
Hong Kong SAR
ZIP/Postal Code
999077
Country
Hong Kong
Facility Name
Pediatric Neurology Unit, Catholic University
City
Essen
ZIP/Postal Code
00168
Country
Italy
Facility Name
Istituto Giannina Gaslini, Centro Traslazionale di Miologia
City
Genova
ZIP/Postal Code
16147
Country
Italy
Facility Name
Department of Neuroscience, Università di Messina, AOU Polic
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
Aichi Children's Health and Medical Center
City
Obu
State/Province
Aichi
ZIP/Postal Code
474-0038
Country
Japan
Facility Name
Hyogo College of Medicine
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
Tokyo Women's Medical University
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
162-8666
Country
Japan
Facility Name
Kumamoto University Hospital
City
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Miyagi Prefectural Children Hospital
City
Miyagi
ZIP/Postal Code
989-3126
Country
Japan
Facility Name
University of Miyazaki Hospital
City
Miyazaki
ZIP/Postal Code
889-1692
Country
Japan
Facility Name
Seoul National University Hospital
City
Seoul
State/Province
Korea
ZIP/Postal Code
3080
Country
Korea, Republic of
Facility Name
Hospital Sant Joan de Deu
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitario Vall de Hebron
City
Hebron
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
The Queen Silvia Children's Hospital
City
Gothenburg
ZIP/Postal Code
SE 416 86
Country
Sweden
Facility Name
Uníversity of Hacettepe
City
Ankara
ZIP/Postal Code
6100
Country
Turkey
Facility Name
Marmara University Pendik Training and Research Hospital
City
Istanbul
ZIP/Postal Code
34662
Country
Turkey
Facility Name
MRC Centre for Neuromuscular Diseases at Newcastle
City
Newcastle
State/Province
Northumberland
ZIP/Postal Code
NE1 3BZ
Country
United Kingdom
Facility Name
UCL Institute of Child Health
City
London
ZIP/Postal Code
WC1N 1EH
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.curesma.org
Description
Cure SMA
URL
http://mda.org/disease/spinal-muscular-atrophy
Description
Muscular Dystrophy Association
URL
https://www.rarediseases.org
Description
National Organization for Rare Diseases
Learn more about this trial
A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
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