Clinical Trial: An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1 (NCT01494701)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-label Study to Assess the Safety and Tolerability of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated

Brief Summary: The primary objective of this study is to examine the safety and tolerability of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA) who previously participated in ISIS 396443-CS1 (NCT02865109). The secondary objective was to examine the plasma pharmacokinetics of a single dose of ISIS 396443 administered intrathecally to participants with SMA who previously participated in ISIS 396443-CS1.

Detailed Summary:

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

In August 2016, sponsorship of the trial was transferred to Biogen.


Sponsor: Biogen

Current Primary Outcome:

  • Number of participants that experience Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Up to 24 Weeks ]
  • Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up tp 24 Weeks ]
  • Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to 24 Weeks ]
  • Number of participants with clinically significant physical examination abnormalities [ Time Frame: Up to 24 Weeks ]
  • Number of participants with clinically significant weight abnormalities [ Time Frame: Up to 24 Weeks ]
  • Number of participants with clinically significant laboratory parameters [ Time Frame: Up to 24 Weeks ]
  • Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [ Time Frame: Up to 24 Weeks ]
  • Number of participants who use concomitant medications [ Time Frame: Up to 24 Weeks ]


Original Primary Outcome: The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 24 weeks ]

Current Secondary Outcome:

  • PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax) [ Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing ]
  • PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax) [ Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing ]
  • PK parameters of nusinersen: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf) [ Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing ]
  • PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible [ Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing ]


Original Secondary Outcome: Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing ]

  • the maximal observed plasma drug concentration (Cmax)
  • the time to reach Cmax in plasma (Tmax)
  • the area under the plasma concentrations time curve from the time of the intrathecal dose to the last collected sample (6 hours after dosing)


Information By: Biogen

Dates:
Date Received: January 28, 2013
Date Started: January 2013
Date Completion:
Last Updated: March 30, 2017
Last Verified: March 2017