Clinical Trial: A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal
Brief Summary: The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset SMA. The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.
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:
- Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) [ Time Frame: Up to Day 402 ]
- Time to death or respiratory intervention [ Time Frame: Up to Day 402 ]
Original Primary Outcome: Time to death or permanent ventilation [ Time Frame: Up to 13 months ]
Current Secondary Outcome:
- Percentage of participants who attained Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) [ Time Frame: Up to Day 402 ]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.
- Overall Survival Rate [ Time Frame: Up to Day 402 ]
- Percentage of participants not requiring permanent ventilation [ Time Frame: Up to Day 402 ]
- Percentage of participants who attained Compound Muscular Action Potential (CMAP) [ Time Frame: Up to Day 402 ]CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. Participants with peroneal CMAP amplitude increasing to or maintained at ≥ 1 mV.
- Time to death or respiratory intervention in the subgroups of participants below the study median disease duration [ Time Frame: Up to Day 402 ]
- Time to death or respiratory intervention in the subgroups of participants above the study median disease duration [ Time Frame: Up to Day 402 ]
- Number of participants experiencing Adverse events (AEs) [ Time Frame: Up to Day 402 ]
- Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to Day 402 ]
- Number of participants with clinically significant weight abnormalities [ Time Frame: Up to Day 402 ]
- Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to Day 402 ]
- Number of participants with clinically significant physical examination abnormalities [ Time Frame: Up to Day 402 ]
- Number of participants with clinically significant laboratory assessment abnormalities [ Time Frame: Up to Day 402 ]
- Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities [ Time Frame: Up to Day 402 ]
- Change from Baseline in concomitant medications [ Time Frame: Up to Day 402 ]
Original Secondary Outcome:
- Change from baseline in CHOP INTEND [ Time Frame: At 13 months ]
- Change from baseline in motor milestones [ Time Frame: At 13 months ]
- Percent of subjects not requiring permanent ventilation [ Time Frame: Up to 13 months ]
- Survival rate [ Time Frame: Up to 13 months ]
- Time to death or permanent ventilation in the subgroups of subjects below the study median disease duration [ Time Frame: Up to 13 months ]
- Time to death or permanent ventilation in the subgroups of subjects above the study median disease duration [ Time Frame: Up to 13 months ]
Information By: Biogen
Dates:
Date Received: July 14, 2014
Date Started: July 2014
Date Completion:
Last Updated: March 24, 2017
Last Verified: March 2017