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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02594124
Recruitment Status : Active, not recruiting
First Posted : November 2, 2015
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE October 30, 2015
First Posted Date  ICMJE November 2, 2015
Last Update Posted Date January 30, 2019
Actual Study Start Date  ICMJE November 4, 2015
Estimated Primary Completion Date August 29, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2017)
  • Number of participants experiencing Adverse events (AEs) and/or Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1807 ]
  • Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to Day 1807 ]
  • Number of participants with clinically significant weight abnormalities [ Time Frame: Up to Day 1807 ]
  • Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to Day 1807 ]
  • Number of participants with clinically significant laboratory assessment abnormalities [ Time Frame: Up to Day 1807 ]
  • Number of participants with clinically significant coagulation parameter abnormalities [ Time Frame: Up to Day 1807 ]
  • Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities [ Time Frame: Up to Day 1807 ]
  • Change from Baseline in concomitant medications [ Time Frame: Up to Day 1807 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 30, 2015)
Safety and tolerability as assessed by the incidence of adverse events (AEs) [ Time Frame: Up to Day 985 ]
Change History Complete list of historical versions of study NCT02594124 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
  • Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria [ Time Frame: Up to Day 1807 ]
  • Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) [ Time Frame: Up to Day 1807 ]
  • Time to death or permanent ventilation [ Time Frame: Up to Day 1807 ]
  • Percentage of participants not requiring permanent ventilation [ Time Frame: Up to Day 1807 ]
  • 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 1807 ]
    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 1807 ]
    The HFMSE tests motor function of patients 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 1807 ]
  • Change from Baseline in 6-Minute Walk Test (6MWT) [ Time Frame: Up to Day 1807 ]
    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 1807 ]
    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 1807 ]
  • Change from Baseline in head circumference (for participants up to 36 months of age) [ Time Frame: Up to Day 1807 ]
  • Change from Baseline in chest circumference (for participants up to 36 months of age) [ Time Frame: Up to Day 1807 ]
  • Change from Baseline in arm circumference (for participants up to 36 months of age) [ Time Frame: Up to Day 1807 ]
  • Proportion of CMAP responders [ Time Frame: Up to Day 1807 ]
  • Number of participants with motor milestones achieved [ Time Frame: Up to Day 1807 ]
  • Proportion of participants who achieved standing alone [ Time Frame: Up to Day 1807 ]
  • Proportion of participants who achieved walking with assistance [ Time Frame: Up to Day 1807 ]
  • Number of participants with serious respiratory events [ Time Frame: Up to Day 1807 ]
  • Number of participants hospitalized [ Time Frame: Up to Day 1807 ]
  • Duration of hospitalizations [ Time Frame: Up to Day 1807 ]
  • Change from Baseline in Cobb-Angle on X-Ray of the thoracolumbar spine [ Time Frame: Up to Day 1807 ]
  • Change from Baseline in Quality of Life (QOL) Questionnaires [ Time Frame: Up to Day 1807 ]
  • Number of Disease-related hospitalizations and AEs [ Time Frame: Up to Day 1807 ]
  • Overall survival rate [ Time Frame: Up to Day 1807 ]
Original Secondary Outcome Measures  ICMJE
 (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  ICMJE A Study for Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in Nusinersen (ISIS 396443) Investigational Studies.
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
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  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 19, 2017)
292
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2015)
274
Estimated Study Completion Date  ICMJE August 29, 2023
Estimated Primary Completion Date August 29, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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  ICMJE NCT02594124
Other Study ID Numbers  ICMJE 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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP