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An Open-label Safety and Tolerability Study of ISIS SMNRx in Patients With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1

This study has been completed.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc. Identifier:
First received: January 28, 2013
Last updated: July 14, 2014
Last verified: July 2014
This study will test the safety and tolerability of ISIS-SMNRx administered into the spinal fluid as a single injection in patients with Spinal Muscular Atrophy, who previously participated in ISIS 396443-CS1

Condition Intervention Phase
Spinal Muscular Atrophy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Ionis Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 24 weeks ]

Secondary Outcome Measures:
  • 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)

Enrollment: 18
Study Start Date: January 2013
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ISIS-SMNRx
Dose Level 1
Single intrathecal injection

Detailed Description:
This study will test the safety, tolerability, and pharmacokinetics of a single dose of ISIS-SMNRx administered as a single intrathecal injection. The single dose will be studied in patients who previously participated in ISIS 396443-CS1, and all patients will receive active drug.

Ages Eligible for Study:   2 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical signs attributable to Spinal Muscular Atrophy
  • Satisfactory completion of dosing and all study visits in ISIS 396443-CS1 with an acceptable safety profile, per Investigator judgement.
  • Able to complete all study procedures, measurements and visits and parent/patient 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

Exclusion Criteria:

  • Have any new or worsening of existing condition which in the opinion of the Investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in or completing the study.
  • Dosing in ISIS 396443-CS1 within 270 days (9 months) of screening, or longer ago than 450 days (15 months)
  • Dosing in ISIS 396443-CS2
  • 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
  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 identifier: NCT01780246

United States, Massachusetts
Boston Children's Hospital
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
Ionis Pharmaceuticals, Inc.
  More Information

Responsible Party: Ionis Pharmaceuticals, Inc. Identifier: NCT01780246     History of Changes
Other Study ID Numbers: ISIS 396443-CS10
Study First Received: January 28, 2013
Last Updated: July 14, 2014

Keywords provided by Ionis Pharmaceuticals, Inc.:
Spinal Muscular Atrophy
ISIS 396443

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Cord Diseases
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases processed this record on March 27, 2017