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Trial record 1 of 2 for:    NCT01494701
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An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) (SMNRx)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01494701
First Posted: December 19, 2011
Last Update Posted: April 6, 2017
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.
Information provided by (Responsible Party):
Biogen
December 13, 2011
December 19, 2011
April 6, 2017
November 30, 2011
January 31, 2013   (Final data collection date for primary outcome measure)
  • 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 ]
The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 4 weeks ]
Complete list of historical versions of study NCT01494701 on ClinicalTrials.gov Archive Site
Not Provided
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)
Not Provided
Not Provided
 
An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA)
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
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).

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

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

Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Spinal Muscular Atrophy
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
January 31, 2013
January 31, 2013   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
2 Years to 14 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01494701
ISIS 396443 - CS1
Yes
Not Provided
Not Provided
Biogen
Biogen
Not Provided
Study Director: Medical Director Biogen
Biogen
April 2017

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