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

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02594124
First Posted: November 2, 2015
Last Update Posted: August 17, 2017
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.
Information provided by (Responsible Party):
Biogen
  Purpose
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.

Condition Intervention Phase
Spinal Muscular Atrophy Drug: nusinersen Phase 3

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 respiratory intervention [ 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 metre 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 ]

Estimated Enrollment: 289
Actual Study Start Date: November 4, 2015
Estimated Study Completion Date: August 1, 2022
Estimated Primary Completion Date: August 1, 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Participants transitioned from ISIS 396443-CS3B (NCT02193074)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
Experimental: Group 2
Participants transitioned from ISIS 396443-CS4 (NCT02292537)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
Experimental: Group 3
Participants transitioned from ISIS 396443-CS12 (NCT02052791)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
Experimental: Group 4
Participants transitioned from ISIS 396443-CS3A (NCT01839656)
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx

Detailed Description:

This study was initiated and the protocol was registered by Ionis Pharmaceuticals, Inc.

In August 2016, Biogen assumed responsibility for this study.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02594124


  Show 36 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Additional Information:
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02594124     History of Changes
Other Study ID Numbers: ISIS 396443-CS11
2015-001870-16 ( EudraCT Number )
First Submitted: October 30, 2015
First Posted: November 2, 2015
Last Update Posted: August 17, 2017
Last Verified: August 2017

Keywords provided by Biogen:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
ISIS-SMN Rx
ISIS 396443
SHINE
IONIS-SMNRx
IONIS-SMN Rx
Spinraza
nusinersen

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases