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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02594124




Registration number
NCT02594124
Ethics application status
Date submitted
30/10/2015
Date registered
1/11/2015
Date last updated
6/02/2024

Titles & IDs
Public title
A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
Scientific title
An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443
Secondary ID [1] 0 0
2015-001870-16
Secondary ID [2] 0 0
ISIS 396443-CS11
Universal Trial Number (UTN)
Trial acronym
SHINE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - nusinersen

Experimental: Group 1 - Participants transitioned from ISIS 396443-CS3B (NCT02193074)

Experimental: Group 2 - Participants transitioned from ISIS 396443-CS4 (NCT02292537)

Experimental: Group 3 - Participants transitioned from ISIS 396443-CS12 (NCT02052791)

Experimental: Group 4 - Participants transitioned from ISIS 396443-CS3A (NCT01839656)

Experimental: Group 5 - Participants transitioned from 232SM202 (NCT02462759)


Treatment: Drugs: nusinersen
Administered by intrathecal (IT) injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to Day 1814
Primary outcome [2] 0 0
Number of participants with clinically significant vital sign abnormalities
Timepoint [2] 0 0
Up to Day 1814
Primary outcome [3] 0 0
Number of participants with clinically significant weight abnormalities
Timepoint [3] 0 0
Up to Day 1814
Primary outcome [4] 0 0
Number of participants with clinically significant neurological examination abnormalities
Timepoint [4] 0 0
Up to Day 1814
Primary outcome [5] 0 0
Number of participants with clinically significant laboratory assessment abnormalities
Timepoint [5] 0 0
Up to Day 1814
Primary outcome [6] 0 0
Number of participants with clinically significant coagulation parameter abnormalities
Timepoint [6] 0 0
Up to Day 1814
Primary outcome [7] 0 0
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities
Timepoint [7] 0 0
Up to Day 1814
Primary outcome [8] 0 0
Change from Baseline in concomitant medications
Timepoint [8] 0 0
Up to Day 1814
Secondary outcome [1] 0 0
Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria
Timepoint [1] 0 0
Up to Day 1814
Secondary outcome [2] 0 0
Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)
Timepoint [2] 0 0
Up to Day 1814
Secondary outcome [3] 0 0
Time to death or permanent ventilation
Timepoint [3] 0 0
Up to Day 1814
Secondary outcome [4] 0 0
Percentage of participants not requiring permanent ventilation
Timepoint [4] 0 0
Up to Day 1814
Secondary outcome [5] 0 0
Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale
Timepoint [5] 0 0
Up to Day 1814
Secondary outcome [6] 0 0
Change from Baseline in Hammersmith Functional Motor Scale
Timepoint [6] 0 0
Up to Day 1814
Secondary outcome [7] 0 0
Change from Baseline in Revised Upper Limb Module (RULM)
Timepoint [7] 0 0
Up to Day 1814
Secondary outcome [8] 0 0
Change from Baseline in 6-Minute Walk Test (6MWT)
Timepoint [8] 0 0
Up to Day 1814
Secondary outcome [9] 0 0
Change from Baseline in Compound Muscular Action Potential (CMAP)
Timepoint [9] 0 0
Up to Day 1814
Secondary outcome [10] 0 0
Change from Baseline in body length and/or height (for all participants)
Timepoint [10] 0 0
Up to Day 1814
Secondary outcome [11] 0 0
Change from Baseline in head circumference (for participants up to 36 months of age)
Timepoint [11] 0 0
Up to Day 1814
Secondary outcome [12] 0 0
Change from Baseline in chest circumference (for participants up to 36 months of age)
Timepoint [12] 0 0
Up to Day 1814
Secondary outcome [13] 0 0
Change from Baseline in arm circumference (for participants up to 36 months of age)
Timepoint [13] 0 0
Up to Day 1814
Secondary outcome [14] 0 0
Proportion of CMAP responders
Timepoint [14] 0 0
Up to Day 1814
Secondary outcome [15] 0 0
Number of participants with motor milestones achieved
Timepoint [15] 0 0
Up to Day 1814
Secondary outcome [16] 0 0
Proportion of participants who achieved standing alone
Timepoint [16] 0 0
Up to Day 1814
Secondary outcome [17] 0 0
Proportion of participants who achieved walking with assistance
Timepoint [17] 0 0
Up to Day 1814
Secondary outcome [18] 0 0
Number of participants with serious respiratory events
Timepoint [18] 0 0
Up to Day 1814
Secondary outcome [19] 0 0
Number of participants hospitalized
Timepoint [19] 0 0
Up to Day 1814
Secondary outcome [20] 0 0
Duration of hospitalizations
Timepoint [20] 0 0
Up to Day 1814
Secondary outcome [21] 0 0
Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine
Timepoint [21] 0 0
Up to Day 1814
Secondary outcome [22] 0 0
Change from Baseline in Quality of Life (QOL) Questionnaires
Timepoint [22] 0 0
Up to Day 1814
Secondary outcome [23] 0 0
Number of Disease-related hospitalizations and AEs
Timepoint [23] 0 0
Up to Day 1814
Secondary outcome [24] 0 0
Overall survival rate
Timepoint [24] 0 0
Up to Day 1814

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/08/2023
Sample size
Target
Accrual to date
Final
292
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Sydney Children's Hospital Clinical Research Centre - Sydney
Recruitment hospital [2] 0 0
Royal Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Belgium
State/province [17] 0 0
Brussels
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
France
State/province [21] 0 0
Paris 9
Country [22] 0 0
Germany
State/province [22] 0 0
Bayern
Country [23] 0 0
Germany
State/province [23] 0 0
Essen
Country [24] 0 0
Germany
State/province [24] 0 0
Freiburg
Country [25] 0 0
Hong Kong
State/province [25] 0 0
Hong Kong SAR
Country [26] 0 0
Italy
State/province [26] 0 0
Essen
Country [27] 0 0
Italy
State/province [27] 0 0
Genova
Country [28] 0 0
Italy
State/province [28] 0 0
Messina
Country [29] 0 0
Japan
State/province [29] 0 0
Aichi
Country [30] 0 0
Japan
State/province [30] 0 0
Hyogo
Country [31] 0 0
Japan
State/province [31] 0 0
Tokyo
Country [32] 0 0
Japan
State/province [32] 0 0
Kumamoto
Country [33] 0 0
Japan
State/province [33] 0 0
Miyagi
Country [34] 0 0
Japan
State/province [34] 0 0
Miyazaki
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Korea
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Hebron
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Sweden
State/province [39] 0 0
Gothenburg
Country [40] 0 0
Turkey
State/province [40] 0 0
Ankara
Country [41] 0 0
Turkey
State/province [41] 0 0
Istanbul
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Northumberland
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02594124
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries