Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) (SMNRx)

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.
ClinicalTrials.gov Identifier: NCT01494701
Recruitment Status : Completed
First Posted : December 19, 2011
Last Update Posted : April 6, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE December 13, 2011
First Posted Date  ICMJE December 19, 2011
Last Update Posted Date April 6, 2017
Actual Study Start Date  ICMJE November 30, 2011
Actual Primary Completion Date January 31, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2017)
  • Number of participants that experience Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Up to 88 Days ]
  • Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to 88 Days ]
  • Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to 88 Days ]
  • Number of participants with clinically significant physical examination abnormalities [ Time Frame: Up to 88 Days ]
  • Number of participants with clinically significant weight abnormalities [ Time Frame: Up to 88 Days ]
  • Number of participants with clinically significant laboratory parameters [ Time Frame: Up to 88 Days ]
  • Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters [ Time Frame: Up to 88 Days ]
  • Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [ Time Frame: Up to 88 Days ]
  • Number of participants who use concomitant medications [ Time Frame: Up to 88 Days ]
  • PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax) [ Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing ]
  • PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax) [ Time Frame: Plasma at 1, 2, 4 and 20 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 20 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 20 hours after dosing ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 15, 2011)
The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 4 weeks ]
Change History Complete list of historical versions of study NCT01494701 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2011)
Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4 and 20 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 (20 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, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)
Official Title  ICMJE An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy
Brief Summary This objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics of a single dose of nusinersen (ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA).
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 Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx
Study Arms  ICMJE
  • Experimental: Cohort 1 (n=6)
    Intervention: Drug: nusinersen
  • Experimental: Cohort 2 (n=6)
    Intervention: Drug: nusinersen
  • Experimental: Cohort 3 (n=6)
    Intervention: Drug: nusinersen
  • Experimental: Cohort 4 (n=10)
    Intervention: Drug: nusinersen
Publications *

*   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: May 7, 2012)
28
Original Estimated Enrollment  ICMJE
 (submitted: December 15, 2011)
24
Actual Study Completion Date  ICMJE January 31, 2013
Actual Primary Completion Date January 31, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Documented Survival Motor Neuron1 (SMN1) homozygous gene deletion
  • Clinical signs attributable to Spinal Muscular Atrophy (SMA)
  • 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:

  • Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
  • Presence of a gastric feeding tube
  • Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the lumbar puncture (LP) injection procedure
  • Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
  • Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
  • History of brain or spinal cord disease that would interfere with LP procedures or cerebrospinal fluid (CSF) circulation
  • Presence of an implanted shunt for the draining of CSF or an implanted Central Nervous System (CNS) catheter
  • History of bacterial meningitis
  • Clinically significant abnormalities in hematology or clinical chemistry parameters
  • Treatment with another investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent whichever is longer. Any history of gene therapy or cell transplantation
  • Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the participant to undergo study procedures

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 14 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 NCT01494701
Other Study ID Numbers  ICMJE ISIS 396443 - CS1
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
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date April 2017

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