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

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

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 Summary:

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

In August 2016, Biogen assumed responsibility for this study.


Sponsor: Biogen

Current Primary Outcome:

  • 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: Safety and tolerability as assessed by the incidence of adverse events (AEs) [ Time Frame: Up to Day 985 ]

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • 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 ]


Information By: Biogen

Dates:
Date Received: October 30, 2015
Date Started: November 4, 2015
Date Completion: August 1, 2022
Last Updated: April 25, 2017
Last Verified: April 2017