A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies (SHINE)

• ClinicalTrials.gov Identifier: NCT02594124
• Recruitment Status: Completed
• First Posted: November 1, 2015
• Last Update Posted: February 6, 2024
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: October 30, 2015
• First Posted Date: November 1, 2015
• Last Update Posted Date: February 6, 2024
• Actual Study Start Date: November 4, 2015
• Actual Primary Completion Date: August 21, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 18, 2019)

• Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1814 ]
• Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to Day 1814 ]
• Number of participants with clinically significant weight abnormalities [ Time Frame: Up to Day 1814 ]
• Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to Day 1814 ]
• Number of participants with clinically significant laboratory assessment abnormalities [ Time Frame: Up to Day 1814 ]
• Number of participants with clinically significant coagulation parameter abnormalities [ Time Frame: Up to Day 1814 ]
• Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities [ Time Frame: Up to Day 1814 ]
• Change from Baseline in concomitant medications [ Time Frame: Up to Day 1814 ]

• Original Primary Outcome Measures (submitted: October 30, 2015): Safety and tolerability as assessed by the incidence of adverse events (AEs) [ Time Frame: Up to Day 985 ]

Current Secondary Outcome Measures (submitted: November 7, 2021)

• Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria [ Time Frame: Up to Day 1814 ]
• Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) [ Time Frame: Up to Day 1814 ]
• Time to death or permanent ventilation [ Time Frame: Up to Day 1814 ]
• Percentage of participants not requiring permanent ventilation [ Time Frame: Up to Day 1814 ]
• Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale [ Time Frame: Up to Day 1814 ]
  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 [ Time Frame: Up to Day 1814 ]
  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) [ Time Frame: Up to Day 1814 ]
• Change from Baseline in 6-Minute Walk Test (6MWT) [ Time Frame: Up to Day 1814 ]
  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) [ Time Frame: Up to Day 1814 ]
  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) [ Time Frame: Up to Day 1814 ]
• Change from Baseline in head circumference (for participants up to 36 months of age) [ Time Frame: Up to Day 1814 ]
• Change from Baseline in chest circumference (for participants up to 36 months of age) [ Time Frame: Up to Day 1814 ]
• Change from Baseline in arm circumference (for participants up to 36 months of age) [ Time Frame: Up to Day 1814 ]
• Proportion of CMAP responders [ Time Frame: Up to Day 1814 ]
• Number of participants with motor milestones achieved [ Time Frame: Up to Day 1814 ]
• Proportion of participants who achieved standing alone [ Time Frame: Up to Day 1814 ]
• Proportion of participants who achieved walking with assistance [ Time Frame: Up to Day 1814 ]
• Number of participants with serious respiratory events [ Time Frame: Up to Day 1814 ]
• Number of participants hospitalized [ Time Frame: Up to Day 1814 ]
• Duration of hospitalizations [ Time Frame: Up to Day 1814 ]
• Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine [ Time Frame: Up to Day 1814 ]
• Change from Baseline in Quality of Life (QOL) Questionnaires [ Time Frame: Up to Day 1814 ]
• Number of Disease-related hospitalizations and AEs [ Time Frame: Up to Day 1814 ]
• Overall survival rate [ Time Frame: Up to Day 1814 ]

Original Secondary Outcome Measures (submitted: October 30, 2015)

• Efficacy as assessed by time to permanent ventilation or death in subjects with Type 1 SMA [ Time Frame: Up to Day 904 ]
• Efficacy as assessed by CHOP INTEND (Type 1 SMA) or Hammersmith Functional Motor Scale (Type II and Type III SMA) scores [ Time Frame: Up to Day 985 ]
• Efficacy as assessed by the 6 minute walk test in subjects who are able to walk [ Time Frame: Up to Day 985 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies
• Official Title: An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443
• 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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Non-Randomized
Intervention 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.

Primary Purpose: Treatment

• Condition: Spinal Muscular Atrophy

Intervention

Drug: nusinersen

Administered by intrathecal (IT) injection

Other Names:

• ISIS 396443
• Spinraza
• BIIB058
• IONIS SMN Rx
• ISIS SMNRx

Study Arms

• Experimental: Group 1
  Participants transitioned from ISIS 396443-CS3B (NCT02193074)
  Intervention: Drug: nusinersen
• Experimental: Group 2
  Participants transitioned from ISIS 396443-CS4 (NCT02292537)
  Intervention: Drug: nusinersen
• Experimental: Group 3
  Participants transitioned from ISIS 396443-CS12 (NCT02052791)
  Intervention: Drug: nusinersen
• Experimental: Group 4
  Participants transitioned from ISIS 396443-CS3A (NCT01839656)
  Intervention: Drug: nusinersen
• Experimental: Group 5
  Participants transitioned from 232SM202 (NCT02462759)
  Intervention: Drug: nusinersen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 19, 2017): 292
• Original Estimated Enrollment (submitted: October 30, 2015): 274
• Actual Study Completion Date: August 21, 2023
• Actual Primary Completion Date: August 21, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Spain, Sweden, Turkey, United Kingdom, United States
• Removed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT02594124
• Other Study ID Numbers: ISIS 396443-CS11; 2015-001870-16 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen
• Original Responsible Party: Ionis Pharmaceuticals, Inc.
• Current Study Sponsor: Biogen
• Original Study Sponsor: Ionis Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: February 2024