This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01494701
First received: December 13, 2011
Last updated: April 5, 2017
Last verified: April 2017
  Purpose
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).

Condition Intervention Phase
Spinal Muscular Atrophy Drug: nusinersen Phase 1

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • 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 ]

Enrollment: 28
Actual Study Start Date: November 30, 2011
Study Completion Date: January 31, 2013
Primary Completion Date: January 31, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (n=6) Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx
Experimental: Cohort 2 (n=6) Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx
Experimental: Cohort 3 (n=6) Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx
Experimental: Cohort 4 (n=10) Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx

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.

  Eligibility

Ages Eligible for Study:   2 Years to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01494701

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
UT Southwestern Medical Center - Children's Medical Center Dallas
Dallas, Texas, United States, 75207
United States, Utah
University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Additional Information:
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01494701     History of Changes
Other Study ID Numbers: ISIS 396443 - CS1
Study First Received: December 13, 2011
Last Updated: April 5, 2017

Keywords provided by Biogen:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
ISIS-SMN Rx
ISIS 396443
IONIS-SMNRx
IONIS-SMN Rx
Spinraza

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on July 27, 2017