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Trial record 1 of 2 for:    NCT01780246
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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)

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ClinicalTrials.gov Identifier: NCT01780246
Recruitment Status : Completed
First Posted : January 31, 2013
Last Update Posted : April 4, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE January 28, 2013
First Posted Date  ICMJE January 31, 2013
Last Update Posted Date April 4, 2017
Study Start Date  ICMJE January 2013
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
  • 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 Measures  ICMJE
 (submitted: January 28, 2013)
The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 24 weeks ]
Change History Complete list of historical versions of study NCT01780246 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2017)
  • 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 Measures  ICMJE
 (submitted: January 28, 2013)
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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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 in ISIS 396443-CS1
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 Description

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

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • Sprinraza
  • ISIS 396443
  • IONIS-SMN Rx
  • BIIB058
Study Arms  ICMJE Experimental: nusinersen
Intervention: Drug: nusinersen
Publications * Haché M, Swoboda KJ, Sethna N, Farrow-Gillespie A, Khandji A, Xia S, Bishop KM. Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. J Child Neurol. 2016 Jun;31(7):899-906. doi: 10.1177/0883073815627882. Epub 2016 Jan 27.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: July 14, 2014)
18
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2013)
28
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Clinical signs attributable to Spinal Muscular Atrophy
  • Satisfactory completion of dosing and all study visits in ISIS 396443-CS1 (NCT01494701) with an acceptable safety profile, per Investigator judgement.
  • Able to complete all study procedures, measurements and visits and parent/participant has adequately supportive psychosocial circumstances, in the opinion of the investigator
  • Estimated life expectancy > 2 years from Screening
  • Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedure

Key Exclusion Criteria:

  • Have any new or worsening of existing 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.
  • Dosing in ISIS 396443-CS1 (NCT01494701) within 270 days (9 months) of screening, or longer ago than 450 days (15 months)
  • Dosing in ISIS 396443-CS2 (NCT01703988)
  • Hospitalization for surgery (i.e. scoliosis surgery) or pulmonary event within 2 months of screening or planned during the duration of the study
  • Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy any time during the screening period
  • Clinically significant abnormalities in hematology or clinical chemistry parameters
  • Treatment with investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent, whichever is longer. Treatment with valproate or hydroxyurea within 1 months of screening. Any history of gene therapy or cell transplantation

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01780246
Other Study ID Numbers  ICMJE ISIS 396443-CS10
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Biogen
Verification Date March 2017

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